minocycline and Acinetobacter-Infections

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

This study aimed to compare the efficacy and safety of combination therapy with high-dose sulbactam or colistin with additional antibacterial agents for treating multidrug-resistant or extensively drug-resistant Acinetobacter baumannii (MDR-AB or XDR-AB) infections.. We systematically searched PubMed, Embase, Cochrane, and Web of Science (through March 30, 2020) for studies that examined high-dose sulbactam or colistin with additional antibacterial agents as therapy for patients with infections with MDR-AB and XDR-AB. Through a network meta-analysis (NMA), using both direct and indirect evidence, we determined risk ratios and 95% confidence intervals. Primary outcomes included clinical improvement, clinical cure, microbiological eradication, and mortality from any cause. Secondary outcomes included nephrotoxicity.. The NMA included 18 studies and 1835 patients. We found that high-dose sulbactam (≥6 g per day), combined with another single antibacterial agent (levofloxacin or tigecycline), which were the highest ranking in clinical improvement and clinical cure. Still colistin-based combination in drug-resistant Acinetobacter baumannii therapy occupied the main position (the number of studies and patients) in most studies. Colistin combined with additional antibacterial agents was associated with a higher risk of nephrotoxicity.. Therapeutic regimens including high-dose sulbactam in combination with additional antibacterial agents (including colistin) might be one of the promising options for the treatment of MDR-AB or XDR-AB infections and high-quality study will be needed to confirm clinical efficacy.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Minocycline; Network Meta-Analysis; Pharmaceutical Preparations; Sulbactam

Doxycycline and, to a lesser extent, minocycline, have been used for decades to treat various serious systemic infections, but many physicians remain unfamiliar with their spectrum, interpretation of susceptibility results, pharmacokinetic/pharmacodynamic (PK/PD) properties, optimal dosing regimens, and their activity against MRSA, VRE, and multidrug-resistant (MDR) Gram-negative bacilli, e.g., Acinetobacter sp. This article reviews the optimal use of doxycycline and minocycline to treat a variety of infections and when minocycline is preferred instead of doxycycline.

Topics: Acinetobacter; Acinetobacter Infections; Anti-Bacterial Agents; Antimicrobial Stewardship; Disk Diffusion Antimicrobial Tests; Doxycycline; Drug Resistance, Multiple, Bacterial; Humans; Minocycline; Streptococcus; Vancomycin-Resistant Enterococci

To comprehensively compare and rank the efficacy and safety of available treatment options for patients with MDR and XDR Acinetobacter baumannii (AB) infection.. We searched PubMed, Embase and the Cochrane register of trials systematically for studies that examined treatment options for patients with MDR- and XDR-AB infections until April 2016. Network meta-analysis (NMA) was performed to estimate the risk ratio (RR) and 95% CI from both direct and indirect evidence. Primary outcomes were clinical cure and microbiological cure. Secondary outcomes were all-cause mortality and nephrotoxic and non-nephrotoxic adverse events.. A total of 29 studies with 2529 patients (median age 60 years; 65% male; median APACHE II score 19.0) were included. Although there were no statistically significant differences between treatment options, triple therapy with colistin, sulbactam and tigecycline had the highest clinical cure rate. Colistin in combination with sulbactam was associated with a significantly higher microbiological cure rate compared with colistin in combination with tigecycline (RR 1.23; 95% CI 1.03-1.47) and colistin monotherapy (RR 1.21; 95% CI 1.06-1.38). No significant differences in all-cause mortality were noted between treatment options. Tigecycline-based therapy also appeared less effective for achieving a microbiological cure and is not appropriate for treating bloodstream MDR- and XDR-AB infections.. Combination therapy of colistin with sulbactam demonstrates superiority in terms of microbiological cure with a safety profile similar to that of colistin monotherapy. Thus, our findings support the use of this combination as a treatment for MDR- and XDR-AB infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Ventilator-Associated; Sulbactam; Tigecycline; Treatment Outcome

Tigecycline, a derivative of minocycline, is an extended-spectrum antimicrobial agent. It has a restricted approval field in children and the experience of its adoption in clinical practice is reserved for cases of challenging infections. The aim of this review was to summarize evidence regarding the use of tigecycline in infants and children, focusing on the drug's clinical efficacy data and tolerability profile. Areas covered: We have conducted a literature search of the Cochrane Library, EMBASE, and MEDLINE databases, from their inception through 5 January 2017, using the following terms: tigecycline, newborn, infant, child, pediatrics, adolescent, human, clinical trial, and case report. Articles were excluded if they were redundant or not pertinent. Bibliographies of all relevant articles were also evaluated. Seventeen publications were included: 1 pharmacokinetic study, 16 case reports. In the selected publications, the patients' mean age was 4.45 years, 38.7% of children was <3 years old and favorable clinical response was achieved in 74.2% of cases. Expert commentary: Tigecycline may be a considerable option in life-threatening infections in pediatric patients. Its administration is well tolerated and has demonstrated a good clinical response in nonbacteremic patients. However, the available clinical records are limited and more studies are needed.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Anti-Bacterial Agents; Child; Child, Preschool; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Infant; Infant, Newborn; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Staphylococcal Infections; Tigecycline; Treatment Outcome

Given that tigecycline-based combination therapy is recognized as a valuable option for the treatment of tigecycline-resistant Acinetobacter baumannii, we conducted this systematic review and meta-analysis to assess the overall evidence of its effectiveness. The synergy rate was defined as the primary outcome that was calculated separately for time-kill, Etest, and checkerboard microdilution methods. The secondary outcomes were bactericidal activity and the efficacy of combination treatment on the development of resistance. In total, 37 published papers and 16 conference proceedings were included. Nine classes consisting of 22 antibiotic types in combination with tigecycline against 1,159 A. baumannii strains were reported in the analysis. For the time-kill studies, combination therapy showed a synergy rate of 37.9% (95% confidence interval [CI], 30.7-46.5); the highest synergy rate was 67.4% (95% CI, 27.3-91.9) for tigecycline in combination with colistin. Moreover, combination with amikacin or colistin could efficiently inhibit the development of tigecycline resistance. Compared with checkerboard microdilution and Etest methods, time-kill studies always showed higher synergy rates. Altogether, these results suggest that the in vitro tigecycline-based combinations resulted in moderate synergy rates and that several combinations could suppress the resistance of A. baumannii to tigecycline, which should be further confirmed in animal models and clinical trials.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Microbial Sensitivity Tests; Microbial Viability; Minocycline; Tigecycline

Carbapenem-resistant organisms are increasingly common worldwide, particularly in India and are associated with high mortality rates especially in patients with severe infection such as bacteremia. Existing drugs such as carbapenems and polymyxins have a number of disadvantages, but remain the mainstay of treatment. The tetracycline class of antibiotics was first produced in the 1940s. Minocycline, tetracycline derivative, although licensed for treatment of wide range of infections, has not been considered for treatment of multidrug-resistant organisms until recently and needs further in vivo studies. Tigecycline, a derivative of minocycline, although with certain disadvantages, has been frequently used in the treatment of carbapenem-resistant organisms. In this article, we review the properties of minocycline and tigecycline, the common mechanisms of resistance, and assess their role in the management of carbapenem-resistant organisms.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Case-Control Studies; Drug Resistance, Multiple, Bacterial; Genes, MDR; Humans; India; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Minocycline; Tigecycline

Treatment of Acinetobacter baumannii has become a medical challenge because of the increasing incidence of multiresistant strains and a lack of viable treatment alternatives. This systematic review attempts to investigate the changes in resistance of A. baumannii to different classes of antibiotics in Iran, with emphasis on the antimicrobial activity of polymyxin B (PMB) and colistin (COL). Biomedical databases were searched for English-published articles evaluating microbiological activity of various antimicrobial agents, including PMB and COL. Then, the available data were extracted and analyzed. Thirty-one studies, published from 2009 to 2015, were identified which contain data for 3,018 A. baumannii clinical isolates. With the exception of polymyxins and tigecycline (TIG), there was a high rate of resistance to various groups of antibiotics, including carbapenems. The minimum inhibitory concentration (MIC) ranges for PMB and COL on A. baumannii isolates tested were 0.12-64 μg/ml and 0.001-128 μg/ml, respectively. Polymyxins showed adequate activity with no significant trends in the resistance rate during most of the study period. The incidence of resistance to TIG was estimated low from 2% to 38.4% among the majority of A. baumannii. The present systematic review of the published literatures revealed that multidrug-resistant (including carbapenem-resistant) strains of A. baumannii have increased in Iran. In these circumstances, the older antibiotics, such as COL or PMB, preferably in combination with other antimicrobials (rifampicin, meropenem), could be considered as the therapeutic solution against the healthcare-associated infections. Designing rational dosage regimens for patients to maximize the antimicrobial activity and minimize the emergence and prevalence of resistance is recommended.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Humans; Iran; Meropenem; Microbial Sensitivity Tests; Minocycline; Polymyxin B; Rifampin; Thienamycins; Tigecycline

Acinetobacter baumannii is a pathogen of increasing concern, commonly causing outbreaks in the hospital environment. Of particular concern, A. baumannii strains exhibiting resistance to carbapenems, which were previously considered the treatment of choice for infected patients, have dramatically increased worldwide, leaving a few antibacterial choices. Tigecycline, a broad-spectrum modified minocycline derivative, isconsidered as a last resort drug against multidrug-resistant A. baumannii. Though, resistance to tigecycline has emerged and is growing notably following increasing tigecycline usage. Comparative evaluation of the tigecycline resistance rates reported worldwide is challenging due to the absence of official interpretative criteria for in vitro susceptibility testing and the discrepancies among the different susceptibility methodologies used, with broth microdilution being considered the reference method. Tigecycline resistance is mainly associated with resistance-nodulation-cell division (RND)-type transporters, mainly the AdeABC, AdeFGH and AdeIJK efflux pumps, but other resistance mechanisms have also been implicated. Tigecycline is still an attractive choice for A. baumannii, but further investigations are warranted so that treatment of MDR Α. baumannii could be guided by validated in vitro data.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Drug Resistance, Multiple, Bacterial; Humans; Minocycline; Tigecycline

The role of tigecycline in treating multidrug-resistant Acinetobacter baumannii (MDR-AB) infections remains controversial. A systematic review and meta-analysis was performed to assess the efficacy and safety of tigecycline in treating MDR-AB infections. PubMed, Embase and Cochrane Library databases were searched up to 20 September 2015. Studies evaluating the efficacy and/or safety of tigecycline in treating MDR-AB infections were included. PRISMA guidelines were followed and the I(2) method was used for heterogeneity. Seven controlled and seventeen single-arm studies were included. No significant difference was noted when tigecycline was compared with control groups in terms of all-cause mortality (OR=0.87, 95% CI 0.50-1.52; P=0.63) and clinical response (OR=1.58, 95% CI 0.61-4.05; P=0.34). Subgroup analysis indicated that treatment with tigecycline was associated with higher in-hospital mortality (OR=1.57, 95% CI 1.04-2.35; P=0.03). Compared with controls, tigecycline had a significantly lower microbial eradication rate (OR=0.20, 95% CI 0.07-0.59; P=0.003) and trend for longer hospital stay (mean difference, 4.69 days, 95% CI -0.17 to 9.55 days; P=0.06). In comparison with monotherapy, tigecycline combination therapy did not affect mortality, clinical response or microbiological response. Tigecycline was well tolerated in the patient populations studied. The pooled rates of resistance emergence and superinfection during treatment were 12.47% and 19.11%, respectively. These findings disfavour the use of a tigecycline-based regimen for the treatment of MDR-AB infections. Well-designed RCTs are needed to clarify the role of tigecycline for MDR-AB infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Humans; Length of Stay; Minocycline; Survival Analysis; Tigecycline; Treatment Outcome

Intravenous minocycline (Minocin

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Intravenous; Drug Resistance, Multiple, Bacterial; Humans; Minocycline; Randomized Controlled Trials as Topic; Retrospective Studies

Multidrug-resistant (MDR) Acinetobacter baumannii infections have emerged as a serious threat worldwide. As novel agents have yet to be developed, understanding the effectiveness and safety of older antibiotics has become a priority. The purpose of this systematic review was to summarise the available clinical evidence on the use of tetracyclines for the treatment of A. baumannii infections. Ten retrospective studies regarding doxycycline and minocycline for the treatment of 185 A. baumannii infections (of which 65.4% were respiratory infections and 13% were bloodstream infections) in 156 patients were available. In most cases (86.4%), tetracyclines were administered in combination with another agent. The usual dosage of doxycycline or minocycline was 100mg intravenous or per os twice daily (usually with a 200mg loading dose for minocycline). Clinical success was achieved in 120 (76.9%) of 156 patients; in 87 (71.9%) of 121 respiratory infections and in 21 (87.5%) of 24 bloodstream infections. Twenty-two deaths occurred in 100 recorded cases. Microbiological eradication was attained in 72 (71.3%) of 101 available cases and documented microbiological eradication was reached in 59 (66.3%) of 89 available cases. Adverse events were noted in only 1 of 88 cases. Overall, although tetracycline-containing regimens showed encouraging results, more data from larger comparative trials are required to establish a role for these antibiotics in the treatment of MDR A. baumannii infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; Doxycycline; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Humans; Minocycline; Respiratory Tract Infections; Survival Analysis; Treatment Outcome

Carbapenem-resistant Acinetobacter baumannii (CRAB) constitutes an increasing problem worldwide. CRAB bacteremia is associated with a high fatality rate and its optimal treatment has not been established. Early institution of appropriate therapy is shown to improve survival of patients with CRAB bloodstream infection. Regrettably, treatment options are limited. Little information exists about the efficacy of sulbactam for the treatment of CRAB bacteremia. Colistin and tigecycline possess good in vitro activity and represent in many cases the only therapeutic options although clinical data are scarce. The need for a loading dose of colistin has been recently demonstrated to rapidly achieve therapeutic levels. The use of combination therapy is also a matter of debate but current evidence do not support its routine use.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; Carbapenems; Colistin; Drug Synergism; Drug Therapy, Combination; Fosfomycin; Humans; Microbial Sensitivity Tests; Minocycline; Polymyxins; Sulbactam; Tigecycline

Minocycline is an old, safe, second-line antimicrobial agent that has drawn attention over the last few years as a possible therapeutic option against multidrug-resistant Acinetobacter baumannii (MDR-AB) clinical isolates. Recent in vitro and in vivo results indicate that minocycline is a valid, alternative treatment option for minocycline-susceptible MDR-AB. Although effective alone, its administration as monotherapy should be avoided. Combinations with other antimicrobials can reduce the MIC of each component, present synergism and minimize the risk for drug resistance. Owing to its limited solubility in urine, it should be avoided for urinary pathogens. The present article reports all available information regarding its use as a therapeutic option against MDR-AB.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline

Options for treatment of multidrug-resistant (MDR) Acinetobacter baumannii infections are extremely limited. Minocycline intravenous is active against many MDR strains of Acinetobacter, and Clinical and Laboratory Standards Institute breakpoints exist to guide interpretation of minocycline susceptibility results with Acinetobacter. In addition, minocycline intravenous holds a US Food and Drug Administration indication for treatment of infections caused by Acinetobacter. There is an accumulating amount of literature reporting successful use of minocycline intravenous for treatment of serious MDR Acinetobacter infections, particularly for nosocomial pneumonia. These results, coupled with the generally favorable tolerability of minocycline intravenous, support its use as a viable therapeutic option for treatment of MDR Acinetobacter infections.

Topics: Acinetobacter; Acinetobacter Infections; Administration, Intravenous; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Humans; Minocycline

Carbapenem-resistant Acinetobacter baumannii pose a significant threat to hospitalized patients, as therapeutic options are scarse. Alarmingly, rates of carbapenem-resistance in A. baumannii are on the rise and are slowly becoming a routine phenotype for this organism. This review focuses on infection control strategies for identification and control of A. baumannii, as well the available therapeutic options.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aminoglycosides; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Carbapenems; Colistin; Disease Management; Disease Outbreaks; Epidemiological Monitoring; Humans; Minocycline; Tigecycline

Acinetobacter baumannii, recognized as a serious threat in healthcare facilities, has the ability to develop resistance to antibiotics quite easily. This resistance is related to either gene acquisition (horizontal gene transfer) or mutations in the genome, leading to gene disruption, over- or down-expression of genes. The clinically relevant antibiotic resistances in A. baumannii include resistance to aminoglycosides, broad-spectrum cephalosporins, carbapenems, tigecycline and colistin, which are the last resort antibiotics. The intrinsic and acquired resistance mechanisms of A. baumannii are presented here, with special focus on β-lactam resistance. The most up-to-date techniques for identification, including phenotypical and molecular tests, and screening of those emerging resistance traits are also highlighted. The implementation of early detection and identification of multidrug-resistant A. baumannii is crucial to control their spread.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aminoglycosides; Anti-Bacterial Agents; Bacterial Proteins; Bacterial Typing Techniques; beta-Lactam Resistance; beta-Lactamases; Carbapenems; Cephalosporins; Colistin; Drug Resistance, Multiple, Bacterial; Gene Expression; Gene Transfer, Horizontal; Humans; Minocycline; Mutation; Tigecycline

This review highlights the impact of carbapenem-resistant Enterobacteriaceae and carbapenem-resistant Acinetobacter baumannii on patients who have undergone organ transplantation and explores both available and potential agents to treat infections caused by these multidrug-resistant (MDR) pathogens.. Few antimicrobials exist to treat carbapenem-resistant Gram-negative infections, and resistance to salvage therapies is escalating. Organ transplantation appears to be a risk factor for infections with Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae. Isolation of these MDR bacteria is increasing and may be associated with allograft failure and mortality. In the majority of cases, aminoglycosides, polymyxins, and tigecycline have been employed to treat these infections. Anecdotal successes exist but these antibiotics may be unreliable. Few novel agents are in development.. Bacterial infections remain a leading cause of posttransplantation morbidity and mortality. Carbapenem resistance is a significant threat to allograft and patient survival. With few antimicrobials being developed, transplant centers may be forced to make decisions regarding surveillance, empiric antimicrobial regimens, and transplant candidacy in the setting of carriage of MDR pathogens. There is an urgent need for collaborative studies to address the clinical impact of these infections on transplantation.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenems; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Minocycline; Organ Transplantation; Risk Factors; Tigecycline

Acinetobacter baumannii are non-fermentative, Gram-negative bacilli that cause a large number of nosocomial infections worldwide. They are characterized by frequent multiresistance due to multiple mechanisms. As a consequence, infections caused by strains exhibiting resistance to carbapenems and, sometimes, polymyxins, are regularly observed. Sulbactam, colistin and combinations of different antimicrobials have been reported as new therapeutic approaches for infections caused by resistant A baumannii strains. This review focuses on current and potential new drugs, such as rifampin, tigecycline, antimicrobial peptides, efflux pump resistant and inhibitor drugs, and enzyme inhibitors.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Clinical Trials as Topic; Dipeptides; Drug Resistance, Multiple, Bacterial; Enzyme Inhibitors; Humans; Minocycline; Molecular Structure; Rifampin; Tigecycline

This article reviews the clinical experience with tigecycline in the treatment of infections caused by microorganisms with prevalent resistance mechanisms among nosocomial microbiota, as methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, multidrug- resistant Acinetobacter baumannii and enterobacteria producing extended spectrum beta-lactamases. Most of articles found in the literature describe the use of tigecycline in the treatment of severe infections (sepsis and septic shock, nosocomial pneumonia and ventilator-associated pneumonia...) produced by multidrug-resistant microorganisms, in patients with multiple comorbidities (admitted in ICU, with malignancies, transplants and/or immunodepressed...) and in many occasions after failures of previous antibiotic treatments. Favourable outcomes with tigecycline are reported in most articles. However, an accurate global assessment is difficult since, in addition to the described confounding factors, there are concomitant or sequential antibiotic treatments in several communications, and lack of relevant clinical (as comorbidities), microbiological (as susceptibility) and outcome (different criteria by different authors) data in others. More even, the described series are retrospective and lack of control groups. Nevertheless the usefulness of this revision is based on the fact that in daily clinical practice the use of tigecycline will increase, since epidemiology of specific hospital medical units shows multidrug resistance among nosocomial isolates and tigecycline can be one of the scarce available compounds active against multidrug-resistant strains/clones.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cross Infection; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Minocycline; Tigecycline

The epidemiology of nosocomial and community-acquired infections has changed in recent years. Methicillin-resistant Staphylococcus aureus (MRSA), especially community-associated MRSA (CA-MRSA), has emerged as a gram-positive organism with an increasing impact in clinical practice. Infections with Acinetobacter baumannii have become a major cause of morbidity and mortality. Minocycline has significant in vitro activity against MRSA and A. baumannii that is comparable with agents currently used against these organisms. The absence of an intravenous (i.v.) minocycline formulation in recent years has limited its use in seriously ill patients infected with these organisms. However, minocycline i.v. has recently been reintroduced to the US market. The objective of this study was to review available information on the chemistry, mechanism of action, in vitro activity, resistance mechanisms, pharmacokinetics, tolerability and efficacy of minocycline against MRSA and A. baumannii. This article provides suggestions for future studies and potential uses of minocycline and is designed to trigger interest in systematic clinical evaluation of minocycline for patients infected with these organisms. In conclusion, minocycline is an old drug that has the potential to become an important part of the armamentarium against emerging infections such as CA-MRSA and A. baumannii. Owing to its promising profile against these clinically important pathogens as well as excellent pharmacokinetic properties, minocycline merits evaluation in serious infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Drug Resistance, Bacterial; Humans; Methicillin-Resistant Staphylococcus aureus; Minocycline; Staphylococcal Infections; United States

Acinetobacter baumannii (AB) is a gram-negative organism that has emerged recently as a major cause of nosocomial infections, because of the extent of its antimicrobial resistance and its persistence in the hospital environment, where intensive care units are the place of greatest risk for acquiring AB. There is no treatment of choice for AB and it's treatment is based on clinical experience and in vitro susceptibility testing. Also, nowadays Acinetobacter resistance to carbapenems is common and isolates resistant to colistin and polymyxin B have been reported. Tigecycline, the 9-tert-butyl-glycylamido derivative of minocycline, exhibits a broad-spectrum of activity against numerous pathogens, including AB and several reports place it among the antimicrobials with lower MIC for AB. Tigecycline overcomes the two major mechanisms of resistance to tetracyclines (ribosomal protection and efflux), but tigecycline resistance emerging during therapy has been reported. Tigecycline efficacy has been demonstrated in clinical studies in skin and skin structure infections and in complicated intra-abdominal infections but, although it seems a good alternative for the treatment of AB infections, there is few evidence about its use in these cases and more clinical experience and adequate trials are needed. The present review shows the recent patents related to treatment by tigecycline in different AB infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cross Infection; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Molecular Structure; Patents as Topic; Structure-Activity Relationship; Tigecycline; Treatment Outcome

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Arizona; Centers for Disease Control and Prevention, U.S.; Colistin; Communicable Diseases, Emerging; Critical Care; Disease Outbreaks; Disease Reservoirs; Drug Resistance, Multiple, Bacterial; Environmental Microbiology; Equipment Contamination; Genes, Bacterial; Genes, MDR; Humans; Infection Control; Minocycline; Nursing Staff, Hospital; Risk Factors; Tigecycline; Total Quality Management; United States

Acinetobacter baumannii is an important cause of nosocomial infections, mainly in patients in intensive care units. This microorganism, although with slight differences depending on the country, presents resistance to multiple antimicrobial agents, occasionally including resistance to colistin: hence, it can be considered the paradigm of nosocomial multiresistant bacteria. This review analyzes the evolution of antimicrobial resistance and the molecular bases associated with the increase in antimicrobial resistance, as well as the current treatment of Acinetobacter infections. Although controversy remains, the pooled data suggest that infections by A. baumannii may be associated with considerable attributable mortality. Moreover, in cases of pneumonia and bacteraemia, inappropriate treatment is associated with, among other factors, mortality. Therefore, treatment should be carefully considered.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Minocycline; Patient Selection; Rifampin; Sulbactam; Tigecycline; Treatment Outcome

New antibacterial agents are required for the treatment of infections caused by multidrug-resistant (MDR) Acinetobacter spp. Whether tigecycline constitutes an effective treatment option or not, is not well established. We sought to evaluate the available evidence regarding the microbiological activity and clinical effectiveness of tigecycline for MDR (including the subset of carbapenem-resistant) Acinetobacter spp.. We searched PubMed for relevant articles and extracted/evaluated the available evidence.. We identified 22 microbiological studies reporting data for 2384 Acinetobacter spp. (1906 Acinetobacter baumannii). Susceptibility of at least 90% of the Acinetobacter isolates to tigecycline (with an MIC breakpoint of susceptibility < or =2 mg/L) was noted in 9/18 studies reporting data on MDR Acinetobacter and in 7/15 studies reporting specific data on carbapenem-resistant Acinetobacter. In an additional study reporting data for both resistance categories, adequate susceptibility of Acinetobacter spp. was observed by one (broth microdilution) of the methods employed. The effectiveness of tigecycline for MDR Acinetobacter infections was evaluated in eight identified clinical studies, reporting retrospective data regarding 42 severely ill patients, among whom 31 had respiratory tract infection (in 4 cases with secondary bacteraemia) and 4 had bacteraemia. Tigecycline therapy (in combination with other antibiotics in 28 patients) was effective in 32/42 cases. In three cases, resistance to tigecycline developed during treatment.. Tigecycline showed considerable, though not consistent, antimicrobial activity against MDR (including carbapenem-resistant) Acinetobacter spp. However, data to support its clinical use, particularly for ventilator-associated pneumonia or bacteraemia, caused by these pathogens, are still limited.

Topics: Acinetobacter; Acinetobacter Infections; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

Acinetobacter baumannii is a highly resilient, gram-negative coccobacillus that thrives within the unique and complex ecological setting of an intensive care unit. This evolving pathogen has now surpassed human capacity to create new antimicrobials, and has led physicians into a concerning era for hospital-acquired infections. This review presents the available evidence on the therapeutic strategies for A. baumannii infection, with a particular focus on clinical human data. The utility of existing and older antimicrobials such as sulbactam and the polymyxins are explored, as well as, the potential role of newer agents such as tigecycline. Other important adjunctive strategies such as pharmacodynamic target attainment and infection control implementation are briefly discussed. It is now clear that new antimicrobials with unique mechanisms of action are urgently required to combat the rising trends seen globally with drug-resistant A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cross Infection; Drug Resistance, Bacterial; Drug Therapy, Combination; Humans; Intensive Care Units; Minocycline; Polymyxins; Sulbactam; Tigecycline

Acinetobacter baumannii and Pseudomonas aeruginosa are gram-negative pathogens that target immunocompromised patients. They express a variety of determinants that confer resistance to a broad array of antimicrobial agents. Mechanisms of resistance include impaired entry through the bacterial outer membrane, production of antibiotic-modifying enzymes, active efflux, and target mutations that reduce antimicrobial affinity. It has been a challenge to identify new agents that have activity against the more resistant variants of these species. Doripenem is a carbapenem in phase 3 trials that has excellent activity against P. aeruginosa and A. baumannii. However, it lacks activity against strains that express resistance to the currently available carbapenems. Tigecycline is a newly licensed glycylcycline that lacks activity against P. aeruginosa but has encouraging activity against many A. baumannii isolates. Resistance to tigecycline can emerge during therapy, however, and is due to expression of multidrug efflux pumps.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Infective Agents; Biofilms; Carbapenems; Clinical Trials as Topic; Doripenem; Drug Resistance, Multiple, Bacterial; Humans; Immunocompromised Host; Minocycline; Pseudomonas aeruginosa; Pseudomonas Infections; Tigecycline

The present study examined the effect of high-dose cefoperazone-sulbactam combined with tigecycline against ventilator-associated pneumonia (VAP) caused by extensively drug-resistant Acinetobacter baumannii(XDR-AB).. 42 patients with VAP due to XDR-AB infection were randomized into two groups: the TIG group (received tigecycline injection) and the TIG+CFS group (received tigecycline and cefoperazone-sulbactam (1 : 1) injection). Pulsed field gel electrophoresis (PFGE) was used for genotyping the isolated XDR-AB. The microdilution method was used to test the minimum inhibitory concentration (MIC) of cefoperazone-sulbactam or tigecycline in vitro and the combined effect was determined with the checkerboard method.. The total combined effectiveness rate (including all patients who demonstrated an improved condition) was significantly higher in the TIG+CFS group (85.7%) compared with the TIG group (47.6%) (p = 0.010). No significant differences were noted with regard to the adverse reactions between the two groups. The 42 isolated XDR-AB strains were classified into four types. The MIC of the two drugs in combination was significantly lower than that of each drug used alone (p < 0.05).. High dose of cefoperazone-sulbactam can improve the antimicrobial activity of tigecycline against XDR-AB.
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Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Cefoperazone; Cohort Studies; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Electrophoresis, Gel, Pulsed-Field; Female; Genotype; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Ventilator-Associated; Prospective Studies; Sulbactam; Tigecycline; Treatment Outcome

We tested 76 extensively drug-resistant (XDR) Acinetobacter baumannii isolates by the checkerboard method using only wells containing serum-achievable concentrations (SACs) of drugs. Checkerboard results were correlated by time-kill assay and clinical outcomes. Minocycline-colistin was the best combination in vitro, as it inhibited growth in one or more SAC wells in all isolates. Patients who received a combination that inhibited growth in one or more SAC wells demonstrated better microbiological clearance than those who did not (88% versus 30%; P = 0.025). The checkerboard platform may have clinical utility for XDR A. baumannii infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Bacterial; Drug Synergism; Drug Therapy, Combination; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Bacterial; Respiratory Tract Infections; Treatment Outcome

The aim of the study was to evaluate the clinical success rate of 73 patients with ventilator-associated pneumonia (VAP) caused by multidrug-resistant (MDR)-Acinetobacter spp. treated with tigecycline in seven intensive Care Units in Argentina and to determine which predictor variables were significant in this context. Clinical success in our patients was 69.86% (Ci= 58.65-81.07%) 51/73, without significant differences between patients with VAP due to MDR-Acinetobacter spp. carbapenem-susceptible or carbapenem-resistant and only susceptible to colistin, minocyline and tigecycline (70% 44/73 vs. 69% 29/73 respectively, p=0.9006), and between patients who received <48h of prior antibiotics (including those who did not receive any) and those who received >48h of prior antibiotics (73.3% 22/30 vs 67.4% 29/43 respectively, p=0.7791). Age >67 and using other method than BAL for respiratory sampling were identified as predicting variables for negative clinical outcome. Our results suggest that tigecycline may be an acceptable alternative for therapy in patients with VAP caused by MDR-Acinetobacter spp. Nevertheless, only controlled clinical trials will provide the evidence to support approval for new indications.

Topics: Acinetobacter; Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bronchoalveolar Lavage; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Minocycline; Pneumonia, Ventilator-Associated; Tigecycline; Treatment Outcome

To evaluate the efficacy and safety of tigecycline in patients with selected serious infections caused by resistant Gram-negative bacteria, or failures who had received prior antimicrobial therapy or were unable to tolerate other appropriate antimicrobials. Secondary objectives included an evaluation of the microbiological efficacy of tigecycline and in vitro activity of tigecycline for resistant Gram-negative bacteria.. This open-label, Phase 3, non-comparative, multicentre study assessed the efficacy and safety of intravenous tigecycline (100 mg initially, then 50 mg 12 hourly for 7-28 days) in hospitalized patients with serious infections including complicated intra-abdominal infection; complicated skin and skin structure infection (cSSSI); community-acquired pneumonia (CAP); hospital-acquired pneumonia, including ventilator-associated pneumonia; or bacteraemia, including catheter-related bacteraemia. All patients had infections due to resistant Gram-negative organisms, including extended-spectrum beta-lactamase-producing strains, or had failed on prior therapy or could not receive (allergy or intolerance) one or more agents from three classes of commonly used antibiotics. The primary efficacy endpoint was clinical response in the microbiologically evaluable (ME) population at test of cure (TOC). Safety data included vital signs, laboratory tests and adverse events (AEs).. In the ME population at TOC, the clinical cure rate was 72.2% [95% confidence interval (CI): 54.8-85.8], and the microbiological eradication rate was 66.7% (95% CI: 13.7-78.8). The most commonly isolated resistant Gram-negative pathogens were Acinetobacter baumannii (47%), Escherichia coli (25%), Klebsiella pneumoniae (16.7%) and Enterobacter spp. (11.0%); the most commonly diagnosed serious infection was cSSSI (67%). The most common treatment-emergent AEs were nausea (29.5%), diarrhoea (16%) and vomiting (16%), which were mild or moderate in severity.. In this non-comparative study, tigecycline appeared safe and efficacious in patients with difficult-to-treat serious infections caused by resistant Gram-negative organisms.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; Drug Resistance, Bacterial; Enterobacter; Enterobacteriaceae Infections; Female; Hospitalization; Humans; Injections, Intravenous; Klebsiella pneumoniae; Male; Middle Aged; Minocycline; Tigecycline; Treatment Outcome

Acinetobacter baumannii (A. baumannii) is an opportunistic pathogen and has emerged as one of the most troublesome pathogens. Drug resistance in A. baumannii has been reported on a global scale. Minocycline was found to be active against multi-drug resistant A. baumannii and was approved by the FDA for the infections caused by sensitive strains of A. baumannii. However, the emergence of minocycline resistance and its toxic effects still need to be addressed. Therefore, this study aimed to evaluate the synergistic effects of metformin combined with minocycline on minocycline-resistant A. baumannii.. The effect of metformin on the antibacterial activity of minocycline was determined by checkerboard and time-killing assay. Further, it was observed by biofilm formation assay that metformin combination with minocycline can inhibit the formation of biofilm. Outer membrane integrity, membrane permeability, membrane potential and reactive oxygen species (ROS) were monitored to explore the underlying synergistic mechanisms of metformin on minocycline. And the results shown that metformin can destroy the outer membrane of A. baumannii, enhance its membrane potential, but does not affect the membrane permeability and ROS.. These findings suggested that the combination of metformin and minocycline has the potential for rejuvenating the activity of minocycline against minocycline-resistant A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Humans; Membrane Potentials; Metformin; Minocycline; Reactive Oxygen Species

Forty-six patients were treated with eravacycline (ERV) for Acinetobacter baumannii infections, where 69.5% of isolates were carbapenem resistant (CRAB). Infections were primarily pulmonary (58.3%), and most patients received combination therapy (84.4%). The median (IQR) ERV duration was 6.9 days (5.1 to 11.1). Thirty-day mortality was 23.9% in the cohort and 21.9% in CRAB patients. One patient experienced an ERV-possible adverse event.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline

The use of tigecycline is becoming increasingly important because of the high levels of antibiotic resistance in

Topics: Acinetobacter baumannii; Acinetobacter Infections; Agar; Anti-Bacterial Agents; Humans; Microbial Sensitivity Tests; Minocycline; Prospective Studies; Tigecycline; United States

Topics: Acinetobacter baumannii; Acinetobacter Infections; Alginates; Animals; Anti-Bacterial Agents; Burns; Female; Gentamicins; Hydrogels; Microbial Sensitivity Tests; Minocycline; Pseudomonas aeruginosa; Pseudomonas Infections; Staphylococcal Infections; Staphylococcus aureus; Swine; Vancomycin; Wound Healing; Wound Infection

In prior research, intrathecal tigecycline was successfully used to treat central nervous system infection by extensively drug-resistant

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Arachnoiditis; Central Nervous System Infections; Drug Resistance, Multiple, Bacterial; Humans; Male; Microbial Sensitivity Tests; Minocycline; Pharmaceutical Preparations; Tigecycline

Unfortunately, the options for treating multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) infections are extremely limited. Recently, fosfomycin and minocycline were newly introduced as a treatment option for MDR A. baumannii infection. Therefore, we investigated the efficacy of the combination of colistin with fosfomycin and minocycline, respectively, as therapeutic options in MDR A. baumannii pneumonia. We examined a carbapenem-resistant A. baumannii isolated from clinical specimens at Severance Hospital, Seoul, Korea. The effect of colistin with fosfomycin, and colistin with minocycline on the bacterial counts in lung tissue was investigated in a mouse model of pneumonia caused by MDR A. baumannii. In vivo, colistin with fosfomycin or minocycline significantly (p < 0.05) reduced the bacterial load in the lungs compared with the controls at 24 and 48 h. In the combination groups, the bacterial loads differed significantly (p < 0.05) from that with the more active antimicrobial alone. Moreover, the combination regimens of colistin with fosfomycin and colistin with minocycline showed bactericidal and synergistic effects compared with the more active antimicrobial alone at 24 and 48 h. This study demonstrated the synergistic effects of combination regimens of colistin with fosfomycin and minocycline, respectively, as therapeutic options in pneumonia caused by MDR A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Carbapenems; Colistin; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Female; Fosfomycin; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Minocycline; Pneumonia; Tigecycline

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacterial Proteins; Carbapenems; Cephalosporins; Colistin; Drug Resistance, Multiple, Bacterial; Lepidoptera; Microbial Sensitivity Tests; Minocycline; Tigecycline; Virulence

Acinetobacter baumannii infections in neonates are not uncommon but rarely studied.. Clinical and molecular epidemiology of 40 patients with A. baumannii bacteremia in the neonatal intensive care units (NICUs) of a medical center from 2004 to 2014 was analyzed.. Multi-drug resistance was found in only 3 isolates (7.5%). Sequence types (STs) of A. baumannii defined by multilocus sequencing typing were diverse, and 72.4% identified isolates belonged to novel STs. Majority of the isolates were susceptible to antibiotics tested. Among the 3 imipenem-resistant A. baumannii (IRAB) isolates, 2 (66.7%) belonged to ST684, a novel ST. All of the 3 isolates were susceptible to tigecycline and colistin. The predominant mechanism of imipenem resistance in these neonatal isolates is ISAba1-bla. To reduce mortality of IRAB infection, it is crucial to consider giving effective agents, such as colistin, in 2 days for high risk neonates who has been given imipenem or used HFOV.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Imipenem; Infant; Infant, Newborn; Intensive Care Units, Neonatal; Male; Microbial Sensitivity Tests; Minocycline; Molecular Epidemiology; Multilocus Sequence Typing; Polymerase Chain Reaction; Risk Factors; Taiwan; Tigecycline

To assess the association of survival and treatment with colistin and tigecycline in critically ill patients with carbapenem-resistant Acinetobacter baumannii bacteraemia.. An observational cohort study was carried out. Targeted therapy consisted of monotherapy with colistin (9 million UI/day) or combined therapy with colistin and tigecycline (100 g/day). The primary outcome was 30-day crude mortality. The association between combined targeted therapy and mortality was controlled for empirical therapy with colistin, propensity score of combined therapy and other potential confounding variables in a multivariate Cox regression analysis.. A total of 118 cases were analysed. Seventy-six patients (64%) received monotherapy and 42 patients (36%) received combined therapy. The source of bacteraemia was primary in 18% (21/118) of the patients, ventilator-associated pneumonia in 64% (76/118) and other sources in 14% (16/118). The 30-day crude mortality rate was 62% (42/76) for monotherapy and 57% (24/42) for combined therapy. The variables associated with 30-day crude mortality were: Charlson index (hazard ratio (HR) 1.16, 95% CI 1.02-1.32; p 0.028), empirical therapy with colistin (HR 2.25, 95% CI 1.33-3.80; p 0.003) and renal dysfunction before treatment (HR 1.91, 95% CI 1.01-3.61; p 0.045). Combined targeted therapy was not associated with lower adjusted 30-day crude mortality (adjusted HR 1.29, 95% CI 0.64-2.58; p 0.494).. Combined targeted therapy with high-dose colistin and standard dose tigecycline was not associated with lower crude mortality of bacteraemia due to carbapenem-resistant A. baumannii in critically ill patients.. Registered in ClinicalTrials.gov. Identifier: NCT02573064.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Bacteremia; Carbapenems; Cohort Studies; Colistin; Critical Illness; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Minocycline; Propensity Score; Survival Analysis; Tigecycline; Treatment Outcome

The higher 14-day mortality rate for patients with Acinetobacter bacteremia receiving tigecycline appropriately compared to other appropriate antibiotics (36.4% versus 14.2%, P = 0.028) was due to the poor effect of tigecycline for isolates with a minimum inhibitory concentration of 2 μg/mL (63.6% of 11 versus 14.2% of 127, P = 0.001).

Topics: Acinetobacter; Acinetobacter baumannii; Acinetobacter calcoaceticus; Acinetobacter Infections; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Mortality; Prospective Studies; Retrospective Studies; Taiwan; Tigecycline; Treatment Outcome

Infections caused by multidrug resistant (MDR) Acinetobacter baumannii (A. baumannii) especially in intensive care units have limited therapeutic options. Overexpression of the adeABC efflux pump may be caused either by the ISAba-1 insertion or by specific point mutations in adeR and adeS, therefore, plays a major role in conferring MDR-A. baumannii. We aimed in our study to monitor the tigecycline (TGC) susceptibility and to study the role of ISAba-1 and the adeS regulator within the AdeABC efflux pump among MDR-A. baumannii clinical isolates. MDR-A. baumannii (63) isolated from ICU patients were identified by detection of OXA-51-like gene. TGC MIC was determined by E-test and broth microdilution. PCR analysis of adeR, adeS, adeB and ISAba1 genes were done with further sequencing of adeS gene. Reduced susceptibility to TGC (MIC: 3-4 mg/L) was noticed in 6/63 (9.5%) MDR-A. baumannii isolates, ISAba-1 was detected in three isolates that two of which showed amino acid substitutions in the adeS operon. We concluded that the amino acids mutations in the adeS gene in presence of insertion ISAba-1 may play a role in conferring reduced TGC susceptibility of MDR-A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; DNA Transposable Elements; Drug Resistance, Multiple, Bacterial; Egypt; Humans; Membrane Transport Proteins; Microbial Sensitivity Tests; Minocycline; Tigecycline

Acinetobacter baumannii is one of the most challenging nosocomial pathogens due to the emergence and widespread of antibiotic resistance. We aimed to provide the first analysis of global prevalence of antibiotic resistance in A. baumannii infections, by synthesizing data and knowledge through a systematic review. We searched studies reporting antibiotic resistance in A. baumannii infections using the Medline, Embase, Web of Science, and Cochrane databases from January 2000 to December 2016. Studies were eligible if they investigated and reported antibiotic resistance in A. baumannii infections with inpatients or outpatients in hospital. Our investigation showed a high prevalence of resistance to the common prescribed antibiotics in A. baumannii infections in both OECD (Organization for Economic Co-operation and Development) and non-OECD countries. Strikingly, though OECD countries have substantially lower pooled prevalence of resistance compared to non-OECD countries based on the data during 2006-2016, a further investigation in a time scale disclosed a faster increase in OECD countries during the past 11 years, and currently both of them have a comparable prevalence of resistance (2011-2016). Tigecycline and colistin are still active but their resistances are expected to become common if the preventative measures are not taken. Antibiotic resistance in A. baumannii infection developed fast and is a crisis for both OECD and non-OECD countries. A "post-antibiotic era" for A. baumannii infection is expected in the next 10-20 years without immediate actions from pharmaceutical companies and governments.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Organisation for Economic Co-Operation and Development; Prevalence; Tigecycline

Acinetobacter baumannii is one of the antibiotic-resistant superbugs that threatens hospitalized patients. Emergence and spread of the multidrug-resistant (MDR) and extensively drug-resistant (XDR) clones cause erratic outbreaks following environmental contamination of hospital settings.. The present study intended to characterize the antimicrobial resistant profiles and the genotypes of clinical and environmental isolates of A. baumannii as a result of dissemination of resistant strains.. Clinical and environmental isolates of A. baumannii were obtained from patients, staff, and environment of an educational hospital in Tehran. Antimicrobial susceptibility testing was carried out using the disk diffusion and E-test methods. Multiplex PCR was performed for detection of OXA-type genes (bla. All the isolates were found to be susceptible to colistin and most of them (77%) were non-susceptible to tigecycline. A majority of the clinical and environmental isolates (97%) were considered as MDR strains and 41% as XDR. In multiplex detection, bla. The present study highlights the circulation of drug-resistant A. baumannii strains in different wards of hospitals principally in intensive care unit (ICU) as a nosocomial pathogen due to unwise managements.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Communicable Diseases, Emerging; Cross Infection; Cross-Sectional Studies; Drug Resistance, Multiple, Bacterial; Genotype; Hospitals, Teaching; Humans; Intensive Care Units; Iran; Minocycline; Molecular Typing; Tigecycline

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adenosine Diphosphate; Adenosine Triphosphate; Anti-Bacterial Agents; Bacterial Proteins; Catalase; Colistin; Gene Deletion; Gene Expression Profiling; Gene Expression Regulation, Bacterial; Gentamicins; Hydrogen Peroxide; Iron; Microbial Sensitivity Tests; Minocycline; Mutation; NAD; Oxidative Stress; Reactive Oxygen Species; Repressor Proteins; Rifampin; Superoxide Dismutase; Tigecycline

Minocycline is one of the few options available to treat infections caused by Acinetobacter baumannii. Acquired resistance to minocycline in A. baumannii is associated with presence of the TetB efflux pump. Previous studies suggested that the absence of tetB may predict minocycline minimum inhibitory concentrations (MICs) of ≤4 µg/mL. In this study, a collection of 258 A. baumannii isolates was used to generate MIC frequency distributions for the tetB-positive and -negative sets of isolates. Of the 93 tetB-negative strains, all had minocycline MICs ≤ 4 µg/mL, resulting in a negative predictive value of 100%. Of the 165 tetB-positive strains, 154 had minocycline MICs > 4 µg/mL, resulting in a positive predictive value of 93.3%. In conclusion, this study shows that tetB is highly associated with MICs above the current US Food and Drug Administration (FDA) and Clinical and Laboratory Standards Institute (CLSI) susceptible breakpoint of 4 µg/mL.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Humans; Membrane Transport Proteins; Microbial Sensitivity Tests; Minocycline; Tetracycline Resistance

Few therapeutic options exist for various infections caused by extensively drug-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii (XDR-Acb) complex isolates, including pneumonia. This study investigated the clinical efficacy between aerosolized colistimethate sodium (AS-CMS, 2 million units thrice a day) treatment alone or in combination with standard-dose tigecycline (TGC) in patients with non-bacteremic pneumonia due to XDR-Acb, and explored the factors influencing patients' 30-day mortality.A 1:1 case (n = 106; receiving TGC plus AS-CMS) control (receiving AS-CMS alone with matching scores) observational study was conducted among adult patients with non-bacteremic XDR-Acb complex pneumonia in a Taiwanese medical center from January 2014 through December 2016. The clinically relevant data were retrospectively recorded. The primary endpoint was 30-day case fatality. Secondary endpoints investigated that if the co-morbidities, XDR-A. baumannii as a pneumonic pathogen, therapy-related factors, or airway colonization with colistin-resistant Acb negatively influenced the 14-day clinical condition of enrolled patients.A higher 30-day mortality rate was noted among the group receiving combination therapy (34.0% vs 22.6%; P = .17). The ≥7-day AS-CMS therapy successfully eradicated > 90% of airway XDR-Acb isolates. Nevertheless, follow-up sputum specimens from 10 (6.4% [10/156]) patients were colonized with colistin-resistant Acb isolates. After the conditional factors were adjusted by multivariate logistic analysis, the only factor independently predicting the 30-day case-fatality was the failure of treating XDR-Acb pneumonia at 14 days (adjusted odds ratio [aOR] = 38.2; 95% confidence interval [CI] = 9.96-142.29; P < .001). Cox proportional regression analysis found that chronic obstructive pulmonary disease (COPD) (adjusted hazard ratio [aHR] = 2.08; 95% CI = 1.05-4.10; P = .035), chronic renal failure (aHR = 3.00; 95% CI = 1.52-5.90; P = .002), non-invasive ventilation use (aHR = 2.68; 95% CI = 1.37-5.25; P = .004), and lack of TGC therapy (aHR = 0.52; 95% CI = 0.27-1.00; P = .049) adversely influenced the 14-day clinical outcomes. Conversely, the emergence of colistin-resistant Acb isolates in the follow-up sputum samples was not statistically significantly associated with curing or improving XDR-Acb pneumonia.In conclusion, aggressive pulmonary hygiene care, the addition of TGC, and corticosteroid dose tapering were beneficial in improving the

Topics: Acinetobacter; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Case-Control Studies; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Minocycline; Pneumonia; Retrospective Studies; Survival Rate; Taiwan; Tigecycline; Treatment Outcome

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Child; Child, Preschool; Colistin; Diabetes Complications; Diabetes Mellitus; Drug Resistance, Bacterial; Female; Hospitalization; Humans; Infant; Infant, Newborn; Intensive Care Units; Lebanon; Logistic Models; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Mortality; Prevalence; Respiration, Artificial; Retrospective Studies; Risk Factors; Shock, Septic; Steroids; Tigecycline; Treatment Outcome; Young Adult

The successful use of tigecycline in a 12-month old liver transplant recipient with extensively drug-resistant Acinetobacter baumannii bacteremia is presented. Tigecycline serum concentrations were monitored to help improve antibiotic efficacy and minimize side effects. A literature review identified 11 additional pediatric cases of A. baumannii infection treated with tigecycline since 2011. Tigecycline treatment should be considered in children with extensively drug-resistant bacterial infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; Drug Resistance, Bacterial; Humans; Infant; Liver Transplantation; Male; Minocycline; Tigecycline

During recent decades, the rates of multidrug resistance, including resistance to carbapenems, have increased dramatically among Acinetobacter species. Tigecycline has activity against multidrug-resistant Acinetobacter spp, including carbapenem-resistant isolates. However, reports of tigecycline-resistant Acinetobacter spp are emerging from different parts of the world. The purpose of this study was to evaluate potential risk factors associated with tigecycline non-susceptible Acinetobacter bacteremia.. The medical records of 152 patients with Acinetobacter bacteremia attending Samsung Medical Center between January 2010 and December 2014 were reviewed. Non-susceptibility to tigecycline was defined as a minimum inhibitory concentration (MIC) of tigecycline ≥4μg/ml. Cases were patients with tigecycline non-susceptible Acinetobacter bacteremia and controls were those with tigecycline-susceptible Acinetobacter bacteremia.. Of the 152 patients included in the study, 61 (40.1%) had tigecycline non-susceptible Acinetobacter bacteremia (case group). These patients were compared to 91 patients with tigecycline-susceptible Acinetobacter bacteremia (control group). The case group showed high resistance to other antibiotics (>90%) except colistin (6.6%) and minocycline (9.8%) when compared to the control group, which exhibited relatively low resistance to other antibiotics (<50%). Multivariate analysis showed that recent exposure to corticosteroids (minimum 20mg per day for more than 5 days within 2 weeks) (adjusted odds ratio (OR) 2.887, 95% confidence interval (CI) 1.170-7.126) and carbapenems (within 2 weeks) (adjusted OR 4.437, 95% CI 1.970-9.991) were significantly associated with tigecycline non-susceptible Acinetobacter bacteremia. Although prior exposure to tigecycline was more common in the case group than in the control group (9.8%, 6/61 vs. 2.2%, 2/91; p=0.046), this variable was found not to be a significant factor associated with tigecycline non-susceptibility after adjustment for other variables (adjusted OR 1.884, 95% CI 0.298-11.920; p=0.501).. These data suggest that tigecycline non-susceptible Acinetobacter spp have emerged and disseminated in the hospital in association with a recent exposure to carbapenems and an immunosuppressed state. This indicates that the rational use of antibiotics through a comprehensive antimicrobial stewardship program, especially in immunosuppressed patients, may be essential in limiting the emergence and spread of multidrug-resistant organisms such as tigecycline-resistant Acinetobacter spp, which are difficult to treat.

Topics: Acinetobacter; Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Bacteremia; Carbapenems; Colistin; Disease Susceptibility; Drug Resistance, Bacterial; Female; Humans; Immunocompromised Host; Male; Middle Aged; Minocycline; Risk Factors; Tigecycline

The incidence of infectious spondylodiscitis has been increasing over the last few years. This reflects the expanding elderly and immunocompromised populations and the rising implementation of invasive spinal procedures. Infection may be inoculated into the disc space directly during invasive spinal procedures. Osteomyelitis caused by Acinetobacter species is rare and mainly caused by multidrug-resistant strains.. We present the case of a 72-year-old Greek woman with postoperative spondylodiscitis caused by a multidrug-resistant Acinetobacter baumannii strain that was successfully treated, after she declined surgical treatment, with prolonged and high dosage of tigecycline. She received intravenously administered tigecycline 200 mg per day for 60 days and then 100 mg per day for a total of 102 days and was infection-free.. We reviewed the literature on the role of Acinetobacter baumannii as a cause of osteomyelitis, emphasizing the difficulty of treatment and the potential role of tigecycline in conservative treatment of the infection. We believe that 102 days in total is the longest time that any patient has received tigecycline in the literature, thus our patient is a unique case of successful treatment of spondylodiscitis.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Discitis; Drug Administration Schedule; Drug Resistance, Multiple, Bacterial; Female; Humans; Minocycline; Tigecycline; Treatment Outcome

Intracranial infection with Acinetobacter baumannii is a tough problem due to the presence of multiresistance and drugs poor penetration through the blood brain barrier (BBB). Tigecycline is effective to cure A baumannii, but it can only be used intravenously which is also difficult to pass BBB. So, it will be a breakthrough if intraventricular (IVT) tigecycline is used in the clinical therapy. However, this treatment has been reported quite rarely until now.. We described a case of a 50-year-old male worker whose clinical futures were high fever and cerebral rigidity after neurosurgery.. Intracranial infection with extensive drug resistant (XDR) A baumannii.. The patient was treated with IVT tigecycline.. The symptoms of intracranial infection disappeared. The temperature of this patient decreased to normal and cerebral rigidity disappeared. The cerebrospinal fluid culture became negative, with normal levels of white blood cell, glucose and chlorine.. IVT tigecycline therapy maybe effective to intracranial infection with XDR A baumannii. However, more studies will further demonstrate the therapeutic values of IVT tigecycline to intracranial infection, and not only restricted to A baumannii infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Central Nervous System Infections; Coma; Drug Resistance, Multiple, Bacterial; Humans; Injections, Intraventricular; Male; Middle Aged; Minocycline; Neurosurgical Procedures; Surgical Wound Infection; Tigecycline

Widespread antibiotic use in clinical medicine and the livestock industry has contributed to the global spread of multidrug-resistant (MDR) bacterial pathogens, including

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Bacteriophages; Drug Resistance, Multiple, Bacterial; Gallstones; Humans; Male; Minocycline; Pancreatic Pseudocyst; Pancreatitis, Acute Necrotizing; Phage Therapy

Synergistic combination antimicrobial therapy may provide new options for treatment of MDR infections. However, comprehensive in vitro synergy data are limited and facile methods to perform synergy testing in a clinically actionable time frame are unavailable.. To systematically investigate a broad range of antibiotic combinations for evidence of synergistic activity against a collection of carbapenem-resistant Enterobacteriaceae (CRE) isolates.. We made use of an automated method for chequerboard array synergy testing based on inkjet printer technology in the HP D300 digital dispenser to test 56 pairwise antimicrobial combinations of meropenem, aztreonam, cefepime, colistin, gentamicin, levofloxacin, chloramphenicol, fosfomycin, trimethoprim/sulfamethoxazole, minocycline and rifampicin, as well as the double carbapenem combination of meropenem and ertapenem.. In a screening procedure, we tested these combinations against four CRE strains and identified nine antibiotic combinations that showed potential clinically relevant synergy. In confirmatory testing using 10 CRE strains, six combinations demonstrated clinically relevant synergy with both antimicrobials at the minimum fractional inhibitory concentration (FICI-MIN) in the susceptible or intermediate range in at least one trial. These included two novel combinations: minocycline plus colistin and minocycline plus meropenem. In 80% of strains at least one combination demonstrated clinically relevant synergy, but the combinations that demonstrated synergy varied from strain to strain.. This work establishes the foundation for future systematic, broad-range investigations into antibiotic synergy for CRE, emphasizes the need for individualized synergy testing and demonstrates the utility of inkjet printer-based technology for the performance of automated antimicrobial synergy assays.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Automation; Aztreonam; Carbapenem-Resistant Enterobacteriaceae; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests; Minocycline; Rifampin; Technology, Pharmaceutical

Acinetobacter baumannii is currently considered as one of the most common successful pathogens in the healthcare system due to its ability to quickly develop resistance. Ten carbapenem-resistant A. calcoaceticus-baumannii complex were isolated from the eastern region, Saudi Arabia in 2014. All isolates were resistant to ciprofloxacin, however, 8 of 10 isolates were tigecycline resistant. Susceptibility test was also carried out for three aminoglycosides, resistance to gentamicin was 80%, amikacin was 90%, and tobramycin was 50%. Colistin susceptibility was seen in all isolates. The 10 isolates harbored bla

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aminoglycosides; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Ciprofloxacin; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Gene Expression Regulation, Bacterial; Gene Transfer, Horizontal; Humans; Microbial Sensitivity Tests; Minocycline; Phylogeny; Plasmids; Polymerase Chain Reaction; Prevalence; Public Health Surveillance; Saudi Arabia; Tigecycline

A rapid increase was observed in the incidence of extensively drug-resistant Acinetobacter baumannii (XDR Aba) isolates in a Greek hospital during 2014. To investigate the causes of this rise, the antimicrobial resistance profiles of all carbapenem-resistant (CARB-R) Aba isolates recovered during 2014-2015 were determined. Selected XDR Aba isolates (n = 13) were characterized by molecular methods. XDR Aba (48 isolates) represented 21.4% of the 224 CARB-R Aba recovered during the study period. The 13 selected XDR Aba isolates were positive for the blaOXA-23, the intrinsic blaOXA-51, and the adeB gene of the AdeABC efflux pump, and all belonged to the 3LST ST101, corresponding to the international clone II. Three bloodstream isolates possessed two amino acid substitutions (A138T+A226V) in the deduced amino acid sequences of the pmrB gene, which may be implicated in colistin resistance. This study demonstrates that this clone still evolves by obtaining an ever-increasing arsenal of antibiotic resistance mechanisms. The clinical characteristics of the intensive care unit (ICU) patients with XDR Aba were reviewed retrospectively. Infected ICU patients with XDR Aba displayed higher death rates compared with infected ICU patients susceptible to colistin and tigecycline CARB-R Aba, although there were no statistically significant differences. Conclusively, continuous surveillance and molecular characterization of XDR Aba, combined with strict infection control measures are mandatory for combating nosocomial infections caused by this organism.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Clone Cells; Colistin; Drug Resistance, Multiple, Bacterial; Female; Gene Expression; Greece; Hospitals; Humans; Intensive Care Units; Male; Membrane Transport Proteins; Microbial Sensitivity Tests; Middle Aged; Minocycline; Mutation; Retrospective Studies; Survival Analysis; Tigecycline; Transcription Factors

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Cephalosporins; Ciprofloxacin; Clone Cells; Colistin; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Gene Expression; Hospitals; Humans; Isoenzymes; Microbial Sensitivity Tests; Minocycline; Molecular Epidemiology; Multilocus Sequence Typing; Saudi Arabia; Serogroup; Tigecycline

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Brazil; Carbapenems; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Polymyxins

Infections due to multidrug- and extensively drug-resistant forms of. Enrolled were patients with MDR-AB or XDR-AB pulmonary infection based on their first sputum culture. Patients were treated empirically with carbapenems (n = 46), tigecycline (n = 25), or cefoperazone/sulbactam (cefina-SB; n = 35). The therapeutic efficacies of the drugs and patient outcomes were retrospectively compared. Bacterial resistance to the three antibacterials was determined based on sputum cultures from all enrolled patients.. The study included 106 patients. After 7 days of treatment, the favorable response rates to tigecycline (60%) and to cefina-SB (71.4%) were statistically similar (p = 0.355) but significantly higher than that to carbapenems (23.9%; p = 0.003 and p < 0.001, respectively). Sputum culture analyses to determine antibiotic susceptibility indicated that 10.4% of patients' sputum cultures were susceptible to carbapenems, 76.4% to tigecycline, and 66.0% to cefina-SB. In addition, 58.5% were susceptible to both tigecycline and cefina-SB.. Tigecycline and cefina-SB appeared to be more effective against MDR-AB and XDR-AB pulmonary infections than carbapenems, especially for patients who had been admitted to the intensive care unit multiple times.
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Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Carbapenems; Cefoperazone; China; Drug Combinations; Drug Resistance, Multiple, Bacterial; Female; Hospitals, Teaching; Humans; Male; Middle Aged; Minocycline; Respiratory Tract Infections; Retrospective Studies; Sputum; Sulbactam; Tigecycline; Time Factors; Treatment Outcome

Identification of risks of mortality for carbapenem-resistant Acinetobacter baumannii (CRAB), with early implementation of an appropriate therapy, is crucial for the patients' outcome. The aim of this study was to survey mortality risk factors in 182 patients with CRAB bacteremia in a medical center in Taiwan.. A total of 182 isolates of CRAB bacteremia were collected from 2009 to 2012 in Mackay Memorial Hospital, Taipei, Taiwan These isolates were identified by using the genotypic method. Risk of attributable mortality analysis was carried out with a Cox proportional hazards model.. The 182 CRAB isolates belonged to 38 different pulsotypes. The attributable mortality rate of the 182 patients was 58.24%. The risk factors for attributable mortality included intensive care unit stay [hazard ratio (HR): 2.27; p = 0.011], an Acute Physiology and Chronic Health Evaluation II score of >20 (HR: 2.19; p < 0.001), respiratory tract as the origin of bacteremia (HR: 3.40; p < 0.001), and previous use of ceftriaxone (HR: 2.51; p = 0.011). The appropriateness of antimicrobial therapy was 18.87% (20/106) in the mortality group versus 88.16% (67/76) in the survivor group (p < 0.001). The sensitivity of CRAB to colistin was 100% and to tigecycline was 40.11%.. The risk factors for mortality for CRAB included intensive care unit stay, a high Acute Physiology and Chronic Health Evaluation II score, respiratory tract as the origin of bacteremia, and previous use of ceftriaxone. Early implementation of an antimicrobial agent that had the highest in vitro activity against CRAB in patients at risk of CRAB bacteremia and high mortality may improve their outcome.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; APACHE; Bacteremia; Carbapenems; Colistin; Drug Resistance, Bacterial; Female; Humans; Intensive Care Units; Male; Microbial Sensitivity Tests; Minocycline; Respiratory Tract Infections; Retrospective Studies; Risk Factors; Tigecycline

To compare the clinical efficacy between salvage antimicrobial regimen consisting of tigecycline plus extended-infusion imipenem/cilastatin (TIC) and regimen of sulbactam plus imipenem/cilastatin (SIC) for patients with ventilator-associated pneumonia and pneumonic bacteremia due to extensively drug-resistant (XDR) Acinetobacter baumannii (Ab) isolates, and determine the correlation of results of in vitro tigecycline-imipenem synergy test with clinical efficacy.. The comparative survey was conducted at a medical center in Taiwan in 2013. Patients comprising the TIC group (n = 28) received tigecycline plus extended-infusion imipenem/cilastatin following unresponsiveness to 3-day sulbactam-imipenem/cilastatin therapy, and those in the SIC group (n = 56) received sulbactam-imipenem/cilastatin throughout the course. Univariate and multivariate analyses were applied to explore 30-day case-fatality independent predictors. Additionally, the checkerboard test and time-kill analysis were performed for the bloodstream XDR-Ab isolates from patients in the TIC group, and molecular characterization was done for the bloodstream XDR-Ab strains of all patients.. We found that the TIC scheme has a significant benefit on improving patients' survival status (the mortality rate of TIC and SIC group patients was 14.3% and 64.3%, respectively), corresponding well with in vitro synergy or additivity results by the checkerboard test. Twenty TIC group cases had monomicrobial XDR-Ab cultured from tracheal aspirates after 10 days of tigecycline-imipenem/cilastatin therapy, but none developed subsequent pneumonia. However, breakthrough primary Burkholderia cepacia (n = 3) and Pseudomonas aeruginosa (n = 1) bacteremias were attributed to four TIC case fatalities. Shock, SIC regimen usage, and development of breakthrough bacteremia were independent predictors of 30-day in-hospital mortality.. Although the TIC regimen showed good efficacy, its value regarding managing XDR-Ab ventilator-associated pneumonia bacteremia needs further evaluation.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Female; Hospital Mortality; Humans; Imipenem; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Ventilator-Associated; Salvage Therapy; Sulbactam; Taiwan; Tigecycline; Treatment Outcome

Acinetobacter baumannii is a significant nosocomial pathogen often associated with extreme drug resistance (XDR). In Argentina, isolates of A. baumannii resistant to tetracyclines have accounted for more than 40% of drug-resistant isolates in some hospitals. We have previously reported the dispersion of the tet(B) resistance element associated with the ISCR2 transposase in epidemiologically unrelated A. baumannii isolates recovered from 1983 to 2011. This study extends this surveillance to 77 recent (2009-2013) XDR A. baumannii isolates with different levels of minocycline susceptibility. Isolates were examined by a pan-PCR assay, which showed six different amplification patterns, and specific PCRs were used for the confirmation of the the ΔISCR2-tet(B)-tet(R)-ISCR2 element. The tet(B) gene was present in 66 isolates and the ISCR2 element in 68 isolates; the tet(B) gene was associated with ISCR2 in all tet(B)-positive isolates. We conclude that this element is widespread in XDR A. baumannii isolates from Argentina and could be responsible for the emergence of tetracycline resistance in recent years.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Argentina; Bacterial Proteins; Hospitals; Humans; Minocycline; Polymerase Chain Reaction; Sequence Analysis, DNA; Tetracycline Resistance

Acinetobacter baumannii infections are difficult to treat owing to the emergence of various antibiotic resistant isolates. Because treatment options are limited for multidrug-resistant (MDR) A. baumannii infection, the discovery of new therapies, including combination therapy, is required. We evaluated the synergistic activity of colistin, doripenem, and tigecycline combinations against extensively drug-resistant (XDR) A. baumannii and MDR A. baumannii.. Time-kill assays were performed for 41 XDR and 28 MDR clinical isolates of A. baumannii by using colistin, doripenem, and tigecycline combinations. Concentrations representative of clinically achievable levels (colistin 2 μg/mL, doripenem 8 μg/mL) and achievable tissue levels (tigecycline 2 μg/mL) for each antibiotic were used in this study.. The colistin-doripenem combination displayed the highest rate of synergy (53.6%) and bactericidal activity (75.4%) in 69 clinical isolates of A. baumannii. Among them, the-doripenem-tigecycline combination showed the lowest rate of synergy (14.5%) and bactericidal activity (24.6%). The doripenem-tigecycline combination showed a higher antagonistic interaction (5.8%) compared with the colistin-tigecycline (1.4%) combination. No antagonism was observed for the colistin-doripenem combination.. The colistin-doripenem combination is supported in vitro by the high rate of synergy and bactericidal activity and lack of antagonistic reaction in XDR and MDR A. baumannii. It seems to be necessary to perform synergy tests to determine the appropriate combination therapy considering the antagonistic reaction found in several isolates against the doripenem-tigecycline and colistin-tigecycline combinations. These findings should be further examined in clinical studies.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Doripenem; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Minocycline; Multilocus Sequence Typing; Tigecycline

The aim of the study was to characterize forty-eight Acinetobacter baumannii (ACB) isolates with confirmed tigecycline MIC values >2 mg/L observed in six Latin American (LATAM) hospitals (four countries) in 2011. During 2005-2011, 6,923 ACB isolates were collected as part of the SENTRY Program, and tigecycline susceptibility was quantified using the reference broth microdilution method. A total of 102/1881 ACB from LATAM hospitals displayed tigecycline minimum inhibitory concentration (MIC) values >2 mg/L, showing an increase from 4.3% in 2010 to 10.5% in 2011, which is considerably high when compared to other geographical regions. Forty-eight ACB from 2011 displaying elevated tigecycline MICs were typed by pulsed-field gel electrophoresis, which showed multiple clusters in Sao Paulo, Brazil, and a major clone in Guadalajara, Mexico. Eighteen unique isolates had the expression of adeA and adeF determined and results compared to a group of tigecycline-susceptible strains, which demonstrated that 18/18 strains had significantly increased expression of AdeABC and three isolates overexpressed AdeFGH. Sequencing of adeS and adeR revealed that 11 isolates displayed adeS mutations, and 5 isolates had mutations in adeR. Sequencing of trm showed frameshift mutations in eight isolates and insertion sequences leading to nonfunctional proteins in three isolates. TetX-encoding genes were not detected. We documented the recent increase of ACB displaying elevated tigecycline MICs in LATAM hospitals, dominantly due to the clonal expansion of isolates in Brazil and Mexico. Control of tigecycline usage in those countries and more strict infection control practices in the involved hospitals should be considered to reduce such outbreaks.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; Clone Cells; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Gene Expression; Genotype; Humans; Latin America; Membrane Transport Proteins; Microbial Sensitivity Tests; Minocycline; Mutation; Prevalence; Tigecycline

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenems; Humans; Microbial Sensitivity Tests; Minocycline; Thailand

Tigecycline has in vitro activity against multidrug-resistant and extensively drug-resistant Acinetobacter baumannii (MDR/XDRAB), and may constitute an alternative therapy for treating pneumonia caused by MDR/XDRAB. The aim of this study was to compare the efficacy of tigecycline-based therapy with colistin-based therapy in patients with MDR/XDRAB pneumonia. Between January 2009 and December 2010, patients in the intensive care unit who were diagnosed with MDR/XDRAB pneumonia and treated with either tigecycline or colistin mono-/combination therapy were reviewed. A total of 70 patients were included in our analysis. Among them, 30 patients received tigecycline-based therapy, and 40 patients received colistin-based therapy. Baseline characteristics were similar in the two groups. Clinical success rate was 47% in the tigecycline group and 48% in the colistin group (P = 0.95). There were no differences between the groups with regard to other clinical outcomes, with the exception that nephrotoxicity was observed only in the colistin group (0% vs. 20%; P = 0.009). Clinical and microbiological success rates were numerically higher, and mortality rates were numerically lower in combination therapy group than in the monotherapy group. Multivariate analysis indicated that monotherapy was independently associated with increased clinical failure (aOR, 3.96; 95% CI, 1.03-15.26; P = 0.046). Our results suggest that tigecycline-based therapy was tolerable and the clinical outcome was comparable to that of colistin-based therapy for patients with MDR/XDRAB pneumonia. In addition, combination therapy may be more useful than monotherapy in treatment of MDR/XDRAB pneumonia.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Minocycline; Pneumonia, Bacterial; Retrospective Studies; Tigecycline; Treatment Outcome

We characterized an outbreak of imipenem-resistant Acinetobacter baumannii with clinical and environmental isolates from a tertiary care hospital in San Luis Potosi, Mexico. During a 4-month period, a total of 32 nonrepetitive imipenem-resistant clinical isolates of A. baumannii were collected. All isolates were susceptible to colistin and tigecycline and resistant to cefepime, ceftazidime, ceftriaxone, imipenem, and meropenem. Genotyping by pulsed-field gel electrophoresis showed a major clone (A). Multilocus sequence type (MLST) analysis was performed, revealing sequence type (ST) 417 (ST417) and 208 (ST208). The blaIMP-, blaVIM-, blaGIM-, blaSIM-, blaNDM-type, and blaOXA-type (blaOXA-23-like, blaOXA-24-like, blaOXA-51-like, and blaOXA-58-like) genes were screened and showed that the blaOXA-51-like and blaOXA-24-like genes were present in all isolates. Sequencing and southern hybridization were performed, confirming the presence of the blaOXA-72 gene and its plasmid-borne nature. In addition, the blaOXA-72-XerC/XerD-like association was identified. These findings indicate that a clonal spread of blaOXA-72-producing A. baumannii ST417 had occurred throughout the hospital. The ST417 corresponded with a previous ST described in the United States.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactamases; beta-Lactams; Colistin; Disease Outbreaks; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Gene Expression; Humans; Isoenzymes; Mexico; Microbial Sensitivity Tests; Minocycline; Multilocus Sequence Typing; Plasmids; Sequence Analysis, DNA; Tertiary Care Centers; Tigecycline

Infections caused by Acinetobacter baumannii are difficult to cure due to the acquisition of resistance by these bacteria and lead to an increase in the general costs of hospitalization. The aim of this study was to determine tigecycline susceptibility of Acinetobacter baumannii strains isolated from intensive care unit and non-intensive care unit patients with skin and soft tissue infections.. MICs were tested by Etest among 70 Acinetobacter baumannii isolates.. The MIC range was from 0.5 to 8.0 mg L⁻¹. For ESBL-producing Acinetobacter baumannii, as well as for strains without carbapenemases, the highest MIC to tigecycline value was 8.0 mg L⁻¹. For AmpC-producing Acinetobacter baumannii, the highest MIC to tigecycline value was 6.0 mg L⁻¹ and, for MBL-producing strains, 2.0 mg L⁻¹.. The majority of Acinetobacter baumannii strains isolated from ICU and non-ICU patients demonstrated high values of MIC range, MIC50 and MIC90 to tigecycline.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Drug Resistance, Multiple, Bacterial; Humans; Intensive Care Units; Microbial Sensitivity Tests; Minocycline; Skin Diseases, Infectious; Soft Tissue Infections; Tigecycline

Eravacycline and comparators were tested against carbapenem- and tigecycline-resistant Enterobacteriaceae and Acinetobacter isolates received at the United Kingdom's national reference laboratory. Eravacycline MICs correlated closely with those of tigecycline but mostly were around 2-fold lower; both molecules retained full activity against isolates with high-level tetracycline and minocycline resistance. MIC90s of eravacycline and tigecycline were raised ca. 2-fold for carbapenem-resistant Enterobacteriaceae compared with carbapenem-susceptible controls, probably reflecting subsets of isolates with increased efflux.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Microbial Sensitivity Tests; Minocycline; Tetracyclines; Tigecycline

Minocycline-based combination therapy has been suggested to be a possible choice for the treatment of infections caused by minocycline-susceptible Acinetobacter baumannii, but its use for the treatment of infections caused by minocycline-resistant A. baumannii is not well established. In this study, we compared the efficacy of minocycline-based combination therapy (with colistin, cefoperazone-sulbactam, or meropenem) to that of colistin in combination with meropenem for the treatment of minocycline-resistant A. baumannii infection. From 2006 to 2010, 191 (17.6%) of 1,083 A. baumannii complex isolates not susceptible to minocycline from the Taiwan Surveillance of Antimicrobial Resistance program were collected. Four representative A. baumannii isolates resistant to minocycline, amikacin, ampicillin-sulbactam, ceftazidime, ciprofloxacin, cefepime, gentamicin, imipenem, levofloxacin, meropenem, and piperacillin-tazobactam were selected on the basis of the diversity of their pulsotypes, collection years, health care setting origins, and geographic areas of origination. All four isolates had tetB and overexpressed adeABC, as revealed by quantitative reverse transcription-PCR. Among all minocycline-based regimens, only the combination with colistin produced a fractional inhibitory concentration index comparable to that achieved with meropenem combined with colistin. Minocycline (4 or 16 μg/ml) in combination with colistin (0.5 μg/ml) also synergistically killed minocycline-resistant isolates in time-kill studies. Minocycline (50 mg/kg of body weight) in combination with colistin (10 mg/kg) significantly improved the survival of mice and reduced the number of bacteria present in the lungs of mice compared to the results of monotherapy. However, minocycline (16 μg/ml)-based therapy was not effective at reducing biofilm-associated bacteria at 24 or 48 h when its effectiveness was compared to that of colistin (0.5 μg/ml) and meropenem (8 μg/ml). The clinical use of minocycline in combination with colistin for the treatment of minocycline-resistant A. baumannii may warrant further investigation.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Biofilms; Cefepime; Cephalosporins; Colistin; Drug Resistance, Multiple, Bacterial; Gentamicins; Imipenem; Meropenem; Mice; Microbial Sensitivity Tests; Minocycline; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia; Taiwan; Thienamycins

Acinetobacter baumannii biofilms are difficult to eradicate. We investigated the effects of meropenem (2 mg/liter), imipenem (2 mg/liter), sulbactam (4 mg/liter), colistin (2 mg/liter), and tigecycline (2 mg/liter), alone or in combination, on biofilm-embedded carbapenem-resistant and carbapenem-susceptible A. baumannii (CRAb and CSAb, respectively) cells, as well as on the architecture of the biofilms. A. baumannii ATCC 15151 (Ab15151) and its OXA-82-overproducing transformant, along with two clinical CSAb and two clinical CRAb isolates of differing clonalities, were used. The minimal bactericidal concentrations for biofilm-embedded cells of the six tested isolates were >50-fold those of their planktonic cells. When used individually, meropenem exhibited a higher killing effect than the other four antimicrobials on biofilm-embedded CSAb cells in the colony biofilm assay. For two clinical CRAb isolates, meropenem plus sulbactam or sulbactam plus tigecycline showed >100-fold the bactericidal effect exhibited by these agents used alone after 48 h of treatment. The effect of antimicrobials on the architecture of Ab15151 biofilm emitting green fluorescence was determined by confocal laser scanning microscopy using COMSTAT software. Significant decreases in the maximum biofilm thickness were observed after exposure to meropenem and imipenem. Meropenem plus sulbactam significantly decreased the biomass and mean thickness and increased the roughness coefficient of biofilms, but sulbactam plus tigecycline only decreased the maximum and mean biofilm thickness compared to any of these agents used alone. Meropenem was active against biofilm-embedded CSAb, whereas meropenem plus sulbactam exhibited synergism against biofilm-embedded CRAb and caused significantly more damage to the biofilm architecture than did any of the agents used alone.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Biofilms; Carbapenems; Colistin; Drug Combinations; Drug Resistance, Bacterial; Drug Synergism; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Minocycline; Sulbactam; Thienamycins; Tigecycline

Tigecycline (Tgc) is considered a last-resort antibiotic for the treatment of multi-drug resistant bacteria. To study Tgc resistance development in the important nosocomial pathogen Acinetobacter baumannii, we adopted six clinical isolates from three patients undergoing antibiotic treatment, and bacterial genomic sequences and seven strand-specific transcriptomes were studied. Interestingly, the Tgc-intermediate 2015ZJAB1 only differed from Tgc-resistant 2015ZJAB2 in an SNP-clustered region including OprD, a sugar-type MFS permease, and a LuxR-type transcriptional regulator. Surprisingly, an almost identical region was found in 2015ZJAB3, which supports the possibility of a homologous recombination event that increased Tgc resistance. Furthermore, comparative transcriptomic analysis identified significantly regulated genes associated with Tgc resistance, which was verified using qRT-PCR. Three enriched COG categories included amino acid transport and metabolism, transcription, and inorganic ion transport and metabolism. KEGG analysis revealed common features under Tgc conditions, including up regulated benzoate degradation and a less active TCA cycle. This may be related to selective antimicrobial pressure in the environment and adaptation by lowering metabolism. This study provides the first report of an in vivo evolutionary process that included a putative homologous recombination event conferring Tgc resistance in clinical A. baumannii isolates in which transcriptome analysis revealed resistance-conferring genes and related metabolism characteristics.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Benzoates; Biological Transport; Citric Acid Cycle; Cross Infection; Evolution, Molecular; Gene Expression Regulation, Bacterial; Homologous Recombination; Humans; Membrane Transport Proteins; Minocycline; Phylogeny; Porins; Repressor Proteins; Tetracycline Resistance; Tigecycline; Trans-Activators; Transcriptome

LpxC inhibitors have generally shown poor in vitro activity against Acinetobacter baumannii We show that the LpxC inhibitor PF-5081090 inhibits lipid A biosynthesis, as determined by silver staining and measurements of endotoxin levels, and significantly increases cell permeability. The presence of PF-5081090 at 32 mg/liter increased susceptibility to rifampin, vancomycin, azithromycin, imipenem, and amikacin but had no effect on susceptibility to ciprofloxacin and tigecycline. Potentiating existing antibiotics with LpxC inhibitors may represent an alternative treatment strategy for multidrug-resistant A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Amidohydrolases; Amikacin; Anti-Bacterial Agents; Azithromycin; Bacterial Proteins; Carbapenems; Drug Resistance, Multiple, Bacterial; Imipenem; Microbial Sensitivity Tests; Minocycline; Rifampin; Tigecycline; Vancomycin

Few effective therapeutic options are available for treating severe infections caused by extensively drug-resistant Acinetobacter baumannii (XDR-AB). Using a murine thigh-infection model, we examined the in vivo efficacy of colistin in combination with meropenem, tigecycline, fosfomycin, fusidic acid, rifampin, or sulbactam against 12 XDR-AB strains. Colistin, tigecycline, rifampin, and sulbactam monotherapy significantly decreased bacterial counts in murine thigh infections compared with those observed in control mice receiving no treatment. Colistin was the most effective agent tested, displaying bactericidal activity against 91.7% of strains at 48 h post-treatment. With strains showing a relatively low minimum inhibitory concentration (MIC) for meropenem (MIC ≤ 32 mg/L), combination therapy with colistin plus meropenem caused synergistic inhibition at both 24 h and 48 h post-treatment. However, when the meropenem MIC was ≥64 mg/L, meropenem did not significantly alter the efficacy of colistin. The addition of rifampin and fusidic acid significantly improved the efficacy of colistin, showing a synergistic effect in 100% and 58.3% of strains after 24 h of treatment, respectively, while the addition of tigecycline, fosfomycin, or sulbactam did not show obvious synergistic activity. No clear differences in activities were observed between colistin-rifampin and colistin-fusidic acid combination therapy with most strains. Overall, our in vivo study showed that administering colistin in combination with rifampin or fusidic acid is more efficacious in treating XDR-AB infections than other combinations. The colistin-meropenem combination may be another appropriate option if the MIC is ≤32 mg/L. Further clinical studies are urgently needed to confirm the relevance of these findings.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Colistin; Drug Combinations; Drug Resistance, Bacterial; Drug Synergism; Fosfomycin; Fusidic Acid; Meropenem; Mice; Microbial Sensitivity Tests; Minocycline; Rifampin; Sulbactam; Thienamycins; Tigecycline

This study assessed the efficacy and safety of tigecycline in children with life-threatening infections.. We retrospectively reviewed the clinical records of patients treated with tigecycline from June 2012 to May 2014 in a Chinese tertiary centre.. The study comprised 24 patients (14 male) with a median age of four years (range, 50 days-12 years). The most frequently isolated microorganism, most common isolation site and type of infection were Acinetobacter baumannii, tracheal aspirate fluid and ventilator-associated pneumonia, respectively. Tigecycline was administered at a loading dose of 1.5 or 2.0 mg/kg and 1.0 mg/kg every 12 hours after that. The average duration of treatment was 11.6 ± 5.8 days. The clinical response and microbiological eradication rate were 37.5% and 29.2%, respectively. Six of the patients we studied (25.0%) died, and three of these deaths were considered to be infection related. Adverse drug reactions were identified in four patients (16.7%) during the treatment, including abnormal liver function, prolonged prothrombin time and diarrhoea.. Our findings suggest that tigecycline may be an option for children with severe infections. However, more prospective, controlled trials are required to objectively evaluate the efficacy and safety of tigecycline in children.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Child; Child, Preschool; Female; Humans; Infant; Male; Minocycline; Pneumonia, Bacterial; Retrospective Studies; Soft Tissue Infections; Tigecycline

Tigecycline is a broad-spectrum antibiotic with activity against multidrug-resistant (MDR) bacteria. It has limited indications. Studies are necessary to elaborate new guidelines. Here we report a case of postoperative MDR Acinetobacter baumannii meningitis treated by tigecycline combined with colimycin for 21 days. The treatment was well tolerated with a favourable outcome. In conclusion, tigecycline was shown to be effective in a case of MDR A. baumannii meningitis.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Male; Meningitis; Microbial Sensitivity Tests; Minocycline; Tigecycline

The treatment options for pneumonia involving multidrug-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii (MDR Acb) complex are limited, and the optimal treatment has not been established.. To compare the efficacy of tigecycline-based with sulbactam (or ampicillin/sulbactam)-based therapy for pneumonia involving MDR Acb complex, we conducted a retrospective study comparing 84 tigecycline-treated adult patients during the period August 2007 to March 2010 with 84 sulbactam or ampicillin/sulbactam-treated adult patients during the period September 2004 to July 2007. Both groups had the matched Acute Physiology and Chronic Health Evaluation (APACHE) II score and received treatment for at least 7 days.. The mean APACHE II score was 20.1 for both groups. More patients in sulbactam group had ventilator use (89.3 % versus 69.0 %), bilateral pneumonia (79.8 % versus 60.7 %) and combination therapy (84.5 % versus 53.6 %), particularly with carbapenems (71.4 % versus 6.0 %), while more patients in tigecycline group had delayed treatment (41.7 % versus 26.2 %) (P <0.05). At the end of treatment, more patients in sulbactam group had airway MDR Acb complex eradication (63.5 % versus 33.3 %, P <0.05). The clinical resolution rate was 66.7 % for both groups. The mortality rate during treatment was 17.9 % in sulbactam group, and 25.0 % in tigecycline group (P = 0.259). The multivariate analysis showed that bilateral pneumonia was the only independent predictor for mortality during treatment (adjusted odds ratio, 2.717; 95 % confidence interval, 1.015 to 7.272).. Patients treated with either tigecycline-based or sulbactam-based therapy had a similar clinical outcome, but tigecycline group had a lower microbiological eradiation rate.

Topics: Acinetobacter baumannii; Acinetobacter calcoaceticus; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Carbapenems; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Minocycline; Pneumonia, Bacterial; Retrospective Studies; Sulbactam; Taiwan; Tigecycline; Treatment Outcome

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Aorta; Colistin; Drug Therapy, Combination; Gentian Violet; Humans; Male; Mediastinitis; Middle Aged; Minocycline; Sulbactam; Tigecycline

Comprehensive data on drug-resistant patterns of Acinetobacter baumannii isolates in developing countries is limited. We conducted a multihospital study to assess the rate and trend of drug-resistant phenotypes in Ac. baumannii using standardized definitions and to determine the remaining therapeutic options against resistant phenotypes. The 401 nonduplicate isolates were collected from six hospitals which are geographically distributed across Tehran, Iran over a 3-year period. Following PCR of bla. The high frequency of drug-resistant phenotypes including carbapenem-resistant Acinetobacter baumannii, multidrug-resistant, and extensively resistant has been demonstrated in Ac. baumannii isolates tested here. As the antibiotic resistance pattern of isolates varies in different geographical regions, this study can provide comprehensive information about the antibiotic resistance profile of Ac. baumannii isolates in Tehran. In addition, the resistance profiles could be effectively considered by clinicians to manage antibiotic therapy. This work also emphasizes on the prudent use of antibiotics and the monitoring of antibiotic susceptibility trend and rate.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Iran; Microbial Sensitivity Tests; Minocycline; Sulbactam; Tigecycline; Tobramycin

Treatment options for infections due to carbapenem-resistant Acinetobacter baumannii are extremely limited. Minocycline is a semisynthetic tetracycline derivative with activity against this pathogen. This study compared susceptibility testing methods that are used in clinical microbiology laboratories (Etest, disk diffusion, and Sensititre broth microdilution methods) for testing of minocycline, tigecycline, and doxycycline against 107 carbapenem-resistant A. baumannii clinical isolates. Susceptibility rates determined with the standard broth microdilution method using cation-adjusted Mueller-Hinton (MH) broth were 77.6% for minocycline and 29% for doxycycline, and 92.5% of isolates had tigecycline MICs of ≤2 μg/ml. Using MH agar from BD and Oxoid, susceptibility rates determined with the Etest method were 67.3% and 52.3% for minocycline, 21.5% and 18.7% for doxycycline, and 71% and 29.9% for tigecycline, respectively. With the disk diffusion method using MH agar from BD and Oxoid, susceptibility rates were 82.2% and 72.9% for minocycline and 34.6% and 34.6% for doxycycline, respectively, and rates of MICs of ≤2 μg/ml were 46.7% and 23.4% for tigecycline. In comparison with the standard broth microdilution results, very major rates were low (∼2.8%) for all three drugs across the methods, but major error rates were higher (∼5.6%), especially with the Etest method. For minocycline, minor error rates ranged from 14% to 37.4%. For tigecycline, minor error rates ranged from 6.5% to 69.2%. The majority of minor errors were due to susceptible results being reported as intermediate. For minocycline susceptibility testing of carbapenem-resistant A. baumannii strains, very major errors are rare, but major and minor errors overcalling strains as intermediate or resistant occur frequently with susceptibility testing methods that are feasible in clinical laboratories.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Doxycycline; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; ATP-Binding Cassette Transporters; Base Sequence; Drug Resistance, Multiple, Bacterial; Gene Editing; Gene Knock-In Techniques; Gene Knockout Techniques; Genome, Bacterial; Microbial Sensitivity Tests; Minocycline; Sequence Analysis, DNA; Tigecycline

The increasing prevalence and global spread of difficult-to-treat carbapenem-resistant Acinetobacter baumannii has become a serious problem. The aim of this study is to investigate the resistance patterns and tigecycline sensitivity of carbapenem-resistant A. baumannii strains.. Acinetobacter strains that were carbapenem-resistant and collected mainly from intensive care units were included into this study. The antibiotic sensitivity/resistance of the strains to other antibiotics and tigecycline were noted. Presence of blaOXA-23, blaOXA-48, blaOXA-58, and NDM-1 was investigated by PCR.. In total, 44 carbapenem-resistant A. baumannii strains were detected. In addition, 57% (25/44) showed resistance to netilmicin and 2% (1/43) to tigecycline. All of the strains were susceptible to colistin. blaOXA-58 was found only in one (2%) strain while blaOXA-23 was found in 14 (32%) strains. All strains were negative for blaOXA-48 and NDM-1.. blaOXA-23 was the main resistance pattern in carbapenem-resistant A. baumannii strains. blaOXA-58 was present only in one strain and no blaOXA-48 was found. Tigecycline susceptibility is high and it can be a treatment option for a possible combination therapy of carbapenem-resistant A. baumannii, especially for those for whom colistin is contraindicated because of its toxicity.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Drug Resistance, Multiple, Bacterial; Microbial Sensitivity Tests; Minocycline; Tigecycline

Acinetobacter baumannii has emerged as an important and problematic pathogen causing bloodstream infections (BSI) in hospitalized patients. Results of an 8-year period from a university hospital are presented. Identification of A. baumannii was performed by Gram-negative BD BBL Crystal ID and VITEK(®)2 system, whereas, susceptibility testing by VITEK2, Kirby-Bauer disc system, and Etest strips. Interpretation of results was based on CLSI criteria and, regarding tigecycline, Food and Drug Administration (FDA) criteria. Between 2006 and 2013, 441 among 7088 BSI cases were attributed to A. baumannii. Of all isolates, 92·1% were resistant to more than three classes of antibiotics and 79·4% were resistant to all but one or two categories of antimicrobials. Resistance to ampicillin-sulbactam, meropenem, gentamicin, ciprofloxacin, minocycline, and tigecycline increased during the study period (P<0·05). Although tigecycline resistance was low during the first 4 years of the study (25·5%), it increased up to 66·5% during 2010-2013. No isolate was colistin resistant.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Minocycline; Tertiary Care Centers; Tigecycline; Time Factors

Over the last decade, multidrug-resistant Acinetobacter baumannii (MDRAB) has emerged as one of the most problematic nosocomial pathogens. Empirical combination therapy has become a common practice to treat patients infected with MDRAB. In vitro interactions of tigecycline with cefoperazone-sulbactam were assessed in 72 MDRAB isolates. Minimum inhibitory concentrations (MICs) were determined by broth microdilution method. Antibiotic interactions were determined by chequerboard and time-kill assays. Chequerboard analysis showed 29·2% synergy and no antagonistic interactions. Time-kill assays confirmed the synergistic interaction between two agents for three of four selected extensively drug-resistant A. baumannii (XDRAB) isolates. No antagonism was revealed by time-kill assays. Moreover, tigecycline in combination with cefoperazone-sulbactam appeared to be more effective than tigecycline in combination with sulbactam against XDRAB. In conclusion, in vitro synergistic activities of tigecycline in combination with cefoperazone-sulbactam against MDRAB were demonstrated, suggesting a superior treatment option against MDRAB.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cefoperazone; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Minocycline; Sulbactam; Tigecycline

Acinetobacter baumannii is the most common species to have developed resistance to antibiotics. Due to increasing levels of drug resistance, the available therapeutic options are insufficient in A. baumannii infections. This study investigated the efficacy of doripenem monotherapy versus doripenem combination therapy with sulbactam, amikacin, colistin and tigecycline in experimental sepsis. A carbapenem-resistant A. baumannii was used to develop a sepsis model in 8-10-week-old Balb/c mice by intraperitoneal injection. Antibiotic therapies were initiated two hours after injection of bacterial suspension. Necropsy was performed at 24, 48 and 72 hours and cultures were made from heart, lung, liver and spleen samples. Bacterial loads of lung and liver were calculated as CFU/g. Combination therapies with doripenem were more effective than monotherapy at 24 and 48 hours of infection but no differences between groups were detected at 72 hours. The combination of doripenem with tigecycline and amikacin began to eradicate the bacterial load of lung and liver after 48 hours of infection, whereas doripenem+sulbactam and doripenem+colistin were started to eradication at 72 hours. The results of the study showed that combination therapies with doripenem are more effective than monotherapy and the combination of doripenem with tigeycline or amikacin has more rapid bactericidal effect than that with sulbactam or colistin.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Amikacin; Animals; Anti-Bacterial Agents; Carbapenems; Colistin; Doripenem; Drug Resistance, Multiple, Bacterial; Humans; Male; Mice; Mice, Inbred BALB C; Minocycline; Sepsis; Sulbactam; Tigecycline

Since few therapeutic options exist for extensively drug resistant Acinetobacter baumannii, an emerging threat in ICUs worldwide, and comparative prospective studies of colistin-based combination therapies are lacking, our objective was to compare the outcomes of patients with extensively drug-resistant A. baumannii bacteremia, treated with colistin-carbapenem and colistin-tigecycline combinations.. Prospective, observational, multicenter study.. Adults with extensively drug-resistant A. baumannii bacteremia were prospectively followed from 2010 to 2013 at three hospitals in Taiwan. Extensively drug-resistant A. baumannii was defined as A. baumannii (genospecies 2) nonsusceptible to all drug classes except for colistin and tigecycline, and standard combination therapy as use of parenteral colistin-carbapenem or colistin-tigecycline for at least 48 hours after onset of bacteremia.. Primary outcome measure was 14-day mortality. Of the 176 episodes of extensively drug-resistant A. baumannii bacteremia evaluated, 55 patients with a median (interquartile range) age of 62 years (44-79 yr) and Sequential Organ Failure Assessment score of 9 (5-13) points received standard combination therapy: colistin-tigecycline in 29 patients and colistin-carbapenem in 26. Crude 14-day and in-hospital mortality rates for patients receiving colistin-tigecycline versus patients receiving colistin-carbapenem were 35% versus 15% (p=0.105) and 69% versus 50% (p=0.152), respectively. Breakthrough extensively drug-resistant A. baumannii bacteremia under steady state concentrations of combination therapy for colistin-tigecycline group was 18% and for colistin-carbapenem group was 0% (p=0.059). Eleven patients (20.0%) developed nephrotoxicity. After adjusting for age, sex, comorbidity, initial disease severity, loading colistin dose, polymicrobial infection, and primary infection site, excess 14-day mortality was associated with the use of colistin-tigecycline in the subgroup with tigecycline minimum inhibitory concentration greater than 2 mg/L compared with the use of colistin-carbapenem (hazard ratio, 6.93; 95% CI, 1.61-29.78; p=0.009).. Increased 14-day mortality was associated with colistin-tigecycline therapy given tigecycline minimum inhibitory concentration greater than 2 mg/L compared with colistin-carbapenem therapy for extensively drug-resistant A. baumannii bacteremia.

Topics: Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Intensive Care Units; Kaplan-Meier Estimate; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Organ Dysfunction Scores; Prospective Studies; Taiwan; Tigecycline

To analyze the expression and regulation of resistance-nodulation-division (RND) efflux systems in clinical tigecycline-nonsusceptible (TNS) Acinetobacter baumannii.. Comparisons of molecular and clinical characteristics were performed between 52 TNS and 53 tigecycline-susceptible isolates. Expression of RND efflux pumps and global regulators were analyzed by real-time RT-PCR. A complementation experiment was performed to evaluate the contribution of the adeRS mutations.. Mechanical ventilation and prior use of carbapenems were more common among patients with TNS strains. The relative expression of adeB and adeJ was increased significantly in TNS isolates. Complementarity to the adeR or adeS mutations decreased tigecycline susceptibility by ≤2-fold. Decreased expression of marR and soxR was detected in TNS isolates.. A correlation between tigecycline MIC and expression level of adeB and adeJ was identified. The influence of adeRS mutation on adeB expression was limited. Global regulators marR and soxR may be involved in tigecycline resistance.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; Drug Resistance, Bacterial; Female; Genes, MDR; Humans; Male; Membrane Transport Proteins; Microbial Sensitivity Tests; Middle Aged; Minocycline; Real-Time Polymerase Chain Reaction; Sequence Deletion; Tigecycline

We describe the clinical outcome of 17 patients with secondary Acinetobacter bacteremia whose isolates had a tigecycline MIC of ≤2 mg/liter and who received tigecycline within 2 days of bacteremia onset. The 14-day mortality rate of the tigecycline cohort was 41.2% (7/17), which was significantly higher than that of those receiving other appropriate antimicrobial agents (13.8%, 9/65; P = 0.018). However, the percentages of end-stage renal disease and congestive heart failure were higher in the tigecycline cohort. The efficacy of tigecycline was contingent upon the illness severity and bacterial species. Tigecycline should be applied cautiously for treatment of Acinetobacter bacteremia.

Topics: Acinetobacter baumannii; Acinetobacter calcoaceticus; Acinetobacter Infections; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Minocycline; Retrospective Studies; Tigecycline

A 74-year-old female patient with end-stage renal disease, undergoing periodic hemodialysis, was hospitalized due to infection by multidrug-resistant Acinetobacter baumannii after hip replacement surgery. She was treated with tigecycline, a glycylcycline agent. Subsequently she developed coagulation disorders as substantiated by increased international normalized ratio (INR), prolonged partial thromboplastin time (aPTT), and severe hypofibrinogenemia, followed by transaminasemia, cholestasis, and anemia. Ultrasonography and computed tomography revealed no underlying pathological entities. Tigecycline was discontinued and the patient underwent daily hemodialysis and received multiple fresh frozen plasma transfusions. Additionally, she was treated with colistin. Her clinical and laboratory status improved. We suggest that patients treated with tigecycline should be monitored for changes in INR, aPTT, and fibrinogen levels to avoid severe, life-threatening coagulation disturbances.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Blood Coagulation Disorders; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; International Normalized Ratio; Kidney Failure, Chronic; Minocycline; Partial Thromboplastin Time; Renal Dialysis; Tigecycline

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; Burns; Child; Child, Preschool; Drug Resistance, Multiple, Bacterial; Humans; Male; Minocycline; Tigecycline; Treatment Outcome

Topics: Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Female; Humans; Male; Minocycline

In 2010 the Hellenic center for disease control and prevention launched the "Prokroustes" nationwide action plan to tackle the increasing rates of carbapenem resistance among gram-negative nosocomial pathogens. In the present report, data from a Greek tertiary-care hospital are presented three years after the adoption of the infection control measures. Carbapenem resistance rates have been contained for Klebsiella pneumoniae and Acinetobacter baumannii but not for Pseudomonas aeruginosa. More worryingly, in accordance with their overuse against carbapenem-resistant bacteria, resistance rates to colistin and tigecycline have risen significantly.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Containment of Biohazards; Cross Infection; Drug Resistance, Multiple, Bacterial; Gentamicins; Greece; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Minocycline; Tertiary Care Centers; Tigecycline

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Young Adult

Minocycline (MIN) usually shows good activity against Acinetobacter baumannii strains. The reintroduction to the market of intravenous MIN provides an additional agent to the limited options for the treatment of A. baumannii infections. The activity of MIN as a single agent and in combination with rifampicin (RIF), colistin (COL) or imipenem (IMI) was evaluated by means of killing curves and 24  h-time-kill curves in five A. baumannii isolates which were selected on the basis of different antimicrobial resistance profiles. MIN showed bacteriostatic activity in three isolates (2 ×  or 16 ×  MIC) and bactericidal activity in the other isolates (64 ×  MIC). In isolates harbouring the tetB gene, the associations studied were always indifferent. However, in isolates not harbouring tetB, the use of MIN in combination showed a rapid synergistic effect (at 4  h) in four out of nine combinations (two with RIF and one each with IMI and COL). At 24  h, this effect was observed in six out of nine combinations (two in each association). MIN in combination with RIF, IMI and COL showed bactericidal synergy in most of the isolates which did not harbour the tetB gene, but the combinations were not synergistic in tetB-positive isolates.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Drug Interactions; Humans; Microbial Sensitivity Tests; Microbial Viability; Minocycline

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cilastatin; Cilastatin, Imipenem Drug Combination; Colistin; Drug Combinations; Drug Resistance, Multiple, Bacterial; Humans; Imipenem; Minocycline; Pneumonia, Ventilator-Associated; Prognosis; Retrospective Studies; Salvage Therapy; Survival Analysis; Tigecycline; Tunisia

An alarming increase in the resistance rates of tigecycline and colistin among carbapenemase-producing Acinetobacter baumannii recovered from a Greek hospital over a 3-year period (2011-2013) was investigated. The antimicrobial resistance profiles and carbapenemase gene content were determined for a collection of colistin- and/or tigecycline-resistant carbapenemase-producing A. baumannii isolates (n = 42), which were recovered consecutively during the study period. A gradual increase in the incidence of blaOXA-23 producers was observed from 2011 to 2013. A cluster of 21 isolates comprised tigecycline-resistant blaOXA-23 producers displayed a single antimicrobial resistance pattern. The emergence of two blaOXA-23 producers resistant to both tigecycline and colistin was documented. Furthermore, determination of the mechanisms of colistin and tigecycline resistance and molecular typing by the tri-locus sequence typing (3LST) scheme for nine isolates recovered from bloodstream infections were performed. Out of nine isolates, five tigecycline- and two colistin-resistant isolates were blaOXA-23 producers of 3LST ST101 corresponding to the international clone II recovered during 2012-2013. All nine isolates were positive for the presence of the adeB gene of the AdeABC efflux pump. Three colistin-resistant isolates possessed novel substitutions in PmrB, which may be implicated in colistin resistance. To the best of our knowledge, this is the first report of the acquisition of tigecycline and colistin resistance among blaOXA-23-producing A. baumannii of 3LST ST101 in Greece; thus, continuous surveillance and molecular characterization, prudent use of antibiotics and implementation of infection control measures for A. baumannii are urgent.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Multiple, Bacterial; Gene Expression Regulation, Bacterial; Gene Expression Regulation, Enzymologic; Greece; Humans; Minocycline; Tigecycline; Time Factors

Carbapenem-resistant Acinetobacter baumannii (CRAB) has emerged as one of the most troublesome pathogens in healthcare settings worldwide. The present study was conducted to analyze the genes encoding resistance to carbapenems and to determine in vitro activity of colistin and tigecycline against CRAB isolates from blood culture of hospitalized patients at Istanbul University Cerrahpasa Medical School hospital.. Between January 2012 and June 2014, a total of 72 CRAB isolates were isolated by conventional methods from blood cultures of patients with bacteremia who were hospitalized in intensive care units and in various departments of the hospital. The isolates were confirmed using a Phoenix automated system. Antibiotic susceptibilities were determined by disk diffusion method and Etest. Molecular detection of resistance genes were screened by multiplex real time polymerase chain reaction (qPCR) and PCR parameters.. CRAB isolates were highly resistant to tetracycline (86.1%), trimethoprim/sulfamethoxazole (84.7%), ceftazidime (83.3%), cefepime (81.9%), ciprofloxacin (81.9%), amikacin (75.0%), piperacillin/tazobactam (75.0%), cefotaxime (72.2%), and gentamicin (69.4%). Tigecycline and colistin resistance were not detected. MIC50 and MIC90 of tigecycline (MIC ranges 0.016-1 µg/mL) and colistin (MIC ranges 0.125-1.5 µg/mL) were found to be 0.5 µg/mL and 1 µg/mL, respectively. All isolates were positive for OXA-51 that shows molecular identification of A. baumannii. Fifty-one (70.8%) and 2 (2.8%) of these isolates were positive for OXA-23 and OXA-58 genes, re- spectively.. This study indicated the most of the CRAB isolates in our hospital carry the OXA-23 gene. Colistin and tigecycline resistance were not detected. However, significant effort must be done to prevent the spread of OXA-23-producing CRAB-isolates and continuous monitoring of drug resistance is necessary in clinical settings.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Bacteremia; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Female; Genotype; Hospitals, University; Humans; Inpatients; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Multiplex Polymerase Chain Reaction; Tigecycline; Turkey

Topics: Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Female; Humans; Male; Minocycline

Topics: Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Female; Humans; Male; Minocycline

Topics: Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Female; Humans; Male; Minocycline

Carbapenem-resistant Acinetobacter baumannii isolates were obtained from 50 patients between July 2011 and July 2012 at the University Hospital A Coruña (NW Spain). These multidrug-resistant isolates, which belonged to a single clone, remained only susceptible to tigecycline, minocycline, and colistin and produced the carbapenem-hydrolyzing oxacillinase, OXA-23. This is the first reported outbreak of OXA-23-producing A. baumannii isolates in Spain.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Clone Cells; Colistin; Cross Infection; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Female; Gene Expression; Hospitals, University; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Spain; Survival Analysis; Tigecycline

Topics: Acinetobacter; Acinetobacter Infections; Anti-Bacterial Agents; Culture Media; Humans; Ions; Microbial Sensitivity Tests; Minocycline; Tigecycline

Colistin and tigecycline have both been shown good in vitro activity among multi-drug resistant Acinetobacter baumannii (MDRAB). A comparative study of colistin versus tigecycline for MDRAB pneumonia is lacking.. The study enrolled adults with MDRAB pneumonia admitted to intensive care units at a referral medical center during 2009-2010. Since there were no standardized minimum inhibitory concentration (MIC) interpretation criteria of tigecycline against A. baumannii, MIC of tigecycline was not routinely tested at our hospital. During the study periods, MIC of colistin was not routinely tested also. We consider both colistin and tigecycline as definite treatments of MDRAB pneumonia. Patients who received tigecycline were selected as potential controls for those who had received colistin. We performed a propensity score analysis, by considering the criteria of age, gender, underlying diseases, and disease severity, in order to match and equalize potential prognostic factors and severity in the two groups.. A total of 294 adults with MDRAB pneumonia were enrolled, including 119 who received colistin and 175 who received tigecycline. We matched 84 adults who received colistin with an equal number of controls who received tigecycline. The two well matched cohorts share similar characteristics: the propensity scores are colistin: 0.37 vs. tigecycline: 0.37, (P = .97); baseline creatinine (1.70 vs. 1.81, P = .50), and the APACHE II score (21.6 vs. 22.0, P = .99). The tigecycline group has an excess mortality of 16.7% (60.7% vs. 44%, 95% confidence interval 0.9% - 32.4%, P = .04). The excess mortality of tigecycline is significant only among those with MIC >2 μg/mL (10/12 vs. 37/84, P = .01), but not for those with MIC ≦ 2 μg/mL (4/10 vs. 37/84, P = .81).. Our data disfavors the use of tigecycline-based treatment in treating MDRAB pneumonia when tigecycline and colistin susceptibilities are unknown, since choosing tigecycline-based treatment might result in higher mortality. The excess mortality of tigecycline-based group may be related to higher MIC of tigecycline (> 2 μg/mL). Choosing tigecycline empirically for treating MDRAB pneumonia in the critical setting should be cautious.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Intensive Care Units; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia; Retrospective Studies; Taiwan; Tigecycline

Colistin and tigecycline are the only therapeutic options for extensively drug resistant Acinetobacter baumannii (XDR-AB), but there is little comparative study. This retrospective observation study evaluated two-colistin and tigecycline-antibiotics profiles like treatment success rate, negative conversion rate, the length of hospital stay, intensive care unit (ICU) stay and antibiotics use, mortality rate during hospital stay and adverse event rate, based on the medical record of XDR-AB positive patients who were treated at least 5 d with those intravenous antibiotics. Treatment success rate of colistin (n=39) and tigecycline (n=16) were not different: 48.7% and 43.8%, respectively (p=0.737), though negative conversion rate was significantly higher in the colistin group: 46.2% against 12.5% (p=0.049). There was no statistically significant difference in mortality rate between two groups during hospital stay (43.6% vs. 56.3%, p=0.393). There were no significant differences in the following parameters: the median length of hospital stay (46.0 d vs. 72.5 d), the median length of intensive care units stay (26.0 d vs. 27.0 d), the median length of antibiotics use (15.0 d vs. 13.0 d). The colistin group showed serum creatinine elevation (defined as elevation more than 2.0 mg/dL and 50% increase from the baseline) as 43.6% when compared with 12.5% of the tigecycline group (p=0.028). As a therapeutic option of XDR-AB, colistin showed significantly better negative conversion rate than tigecycline with more frequent nephrotoxic prevalence, and treatment success rate and mortality rate were not different from both antibiotics groups.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Intravenous; Adult; Aged; Anti-Bacterial Agents; Colistin; Creatinine; Drug Resistance, Multiple, Bacterial; Female; Humans; Intensive Care Units; Kidney; Length of Stay; Male; Middle Aged; Minocycline; Retrospective Studies; Tigecycline; Treatment Outcome

Data for treatment and outcomes of extensively drug-resistant Acinetobacter baumannii (XDR-AB) pneumonia are limited. A retrospective cohort study of 236 adult patients with XDR-AB pneumonia was conducted between January 2009 and December 2012. The median age of subjects was 70 years (range 17-95 years), 53% were male, 55% had ventilator-associated pneumonia and 42% had been admitted to the intensive care unit. All XDR-AB isolates were susceptible only to tigecycline and colistin; 52 (22%) of the 236 subjects did not receive an agent active against XDR-AB, with an associated 28-day survival of 0%. Colistin-based two-drug combination treatment was prescribed to 166 subjects (70%); regimens included (i) colistin and high-dose sulbactam (n=93); (ii) colistin and tigecycline (n=43); and (iii) colistin and high-dose prolonged infusion of a carbapenem (n=30). The 28-day survival rate and mean length of hospital stay were not statistically different between these three regimens (65%, 53% and 60% and 39, 39 and 38 days, respectively). Predictors of mortality included Acute Physiology and Chronic Health Evaluation (APACHE) II score [adjusted odds ratio (aOR)=1.11; P<0.001 for each point increase], duration from infection onset to receipt of active regimen (aOR=1.01; P=0.002 for each hour delay), underlying malignancy (aOR=3.46; P=0.01) and chronic kidney disease (aOR=2.85; P=0.03). These findings suggest that the three colistin-based two-drug combination regimens may be treatment options for XDR-AB pneumonia.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; APACHE; Carbapenems; Cohort Studies; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Minocycline; Pneumonia, Ventilator-Associated; Retrospective Studies; Sulbactam; Tigecycline; Treatment Outcome; Young Adult

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Burns; Cefoperazone; Humans; Meropenem; Middle Aged; Minocycline; Retrospective Studies; Sulbactam; Thienamycins; Young Adult

The shortage of effective antibiotics against multidrug-resistant Acinetobacter baumannii (MDR-Ab) has posed great threat to the public health. But the advent of tigecycline gives us new hope. The goal of our research was to assess the clinical efficacy of tigecycline at different doses by using a pharmacokinetic/pharmacodynamic (PK/PD) model which can incorporate pharmacokinetic data of tigecycline from patients with pneumonia and MICs of MDR-Ab from a tertiary hospital. A 10000-patient Monte-Carlo Simulation based on the PK/PD model was conducted to calculate the probability of target attainment (PTA) and the cumulative fraction of response (CFR) of tigecycline. 97% isolates displayed susceptibility and 3% were tigecycline-intermediate strains and the values of MIC ranged from 0.125 to 4 μ g/ml. A CFR of 61.62% was predicted for tigecycline at current dosage (50 mg q12h). When the dosage was increased, the predicted CFRs for 75 mg q12h, 100 mg q12h, 125 mg q12h, 150 mg q12h were 81.00%, 89.86%, and 94.57%, 96.77%, respectively. Despite presented higher susceptibility, the CFR obtained was not optimal at current dosage. A higher CFR indicating a better clinical efficacy can be gained by the increased dosage.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cross Infection; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Monte Carlo Method; Pneumonia, Bacterial; Tigecycline

Tigecycline (TGC)-resistant extensively drug-resistant Acinetobacter baumannii (XDRAB) is an increasing threat in regard to nosocomial infections. The resistance-nodulation-cell division (RND) efflux pump has played an important role in TGC resistance. In this study, total 81 TGC-resistant XDRAB isolates were analyzed for their responses to the efflux pump inhibitor 1-(1-naphthylmethyl)-piperazine (NMP). We found that NMP could reduce by 4-fold or greater than 4-fold the minimum inhibitory concentration (MIC) of TGC in 45 isolates (55.6 %). After typing with pulsed-field gel electrophoresis (PFGE), group A appeared to be the major cluster with good synergistic response to NMP. Transcripts of the AdeABC efflux pump gene were consistently more correlated with TGC resistance than transcripts of the AdeFGJ or AdeIJK efflux pump genes in these isolates. Of the 81 isolates, the amino acid sequences of AdeR and AdeS were further classified and combined into 31 different codes. Although the dissemination of TGC-resistant XDRAB isolates was genetically diverse in our hospital, their responses to NMP conversion were still strain-dependent. We found that AdeRS combination codes were better than PFGE typing in separating groups of isolates with different sensitivity to NMP conversion.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Humans; Membrane Transport Proteins; Microbial Sensitivity Tests; Minocycline; Tigecycline

Acinetobacter baumannii is an important nosocomial pathogen able to cause severe infections in an intensive care unit (ICU). However, there is a lack of analysis regarding the epidemiology and resistance of A. baumannii in respiratory department ICUs. In this study, clinical isolates were collected from the respiratory department ICU of Southwest Hospital from January 2009 to December 2010, and the social and demographic information of the patients from whom the isolates were taken was obtained from the Southwest Hospital information system. The minimal inhibitory concentration (MIC) of the isolates was determined by the agar dilution method. The carbapenemase-encoding resistance genes of these isolates were amplified using PCR. The clonal relationship of isolates was analyzed by pulsed-field gel electrophoresis (PFGE). Forty-six isolates were collected from the respiratory department ICU, and the antibiotics minocycline and quinolone had higher drug sensitivity against these isolates. The OXA-51, OXA-23, and IMP-4 genes were present at rates of 100% (46/46), 67.4% (31/46), and 41.3% (19/46), respectively. Forty-six isolates had 12 different PFGE genotypes. The results above suggested that the hospital environment and patients contributed to nosocomial infections, and the spread of resistance genes in the hospital was common.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Child; Child, Preschool; China; Cross Infection; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Hospitals; Humans; Infant; Infant, Newborn; Intensive Care Units; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Quinolones; Young Adult

The aim of this study was to investigate the in vitro activities of rifampin, colistin, sulbactam and tigecycline alone and in combination against extensively drug-resistant Acinetobacter baumannii (XDR-Ab). Twenty-five XDR-Ab strains were isolated from patients. Broth microdilution assay was used to determine the minimum inhibitory concentration (MIC) for rifampin, colistin, sulbactam and tigecycline against XDR-Ab strains. The checkerboard microdilution method was used to determine the in vitro activities of potential therapeutic combinations of these four antimicrobial agents. Accordingly, the fractional inhibitory concentration (FIC) and FIC index (FICI) were calculated for each of the combinations. According to our results, when tested as single drugs, rifampin, colistin or tigecycline had good bacteriostatic activity against XDR-Ab, whereas sulbactam was not as active against XDR-Ab isolates. On the other hand, when tested in combination, the combinations of colistin/rifampin, rifampin/sulbactam, rifampin/tigecycline and sulbactam/tigecycline showed good in vitro activities against XDR-Ab isolates. More importantly, these combination regimens could exert addictive or partially synergistic effects at the sub-MIC levels against XDR-Ab strains. Compared with single drugs, most of the combinations of these antimicrobial agents could exert partially synergistic and/or addictive effects, which might provide a better alternative when treating XDR-Ab infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Minocycline; Rifampin; Sulbactam; Tigecycline

Adaptive antibiotic resistance is a newly described phenomenon by which Acinetobacter baumannii induces efflux pump activity in response to host-associated environmental cues that may, in part, account for antibiotic treatment failures against clinically defined susceptible strains. To that end, during adaptation to growth in human serum, the organism induces approximately 22 putative efflux-associated genes and displays efflux-mediated minocycline tolerance at antibiotic concentrations corresponding to patient serum levels. Here, we show that in addition to minocycline, growth in human serum elicits A. baumannii efflux-mediated tolerance to the antibiotics ciprofloxacin, meropenem, tetracycline, and tigecycline. Moreover, using a whole-cell high-throughput screen and secondary assays, we identified novel serum-associated antibiotic efflux inhibitors that potentiated the activities of antibiotics toward serum-grown A. baumannii. Two compounds, Acinetobacter baumannii efflux pump inhibitor 1 (ABEPI1) [(E)-4-((4-chlorobenzylidene)amino)benezenesulfonamide] and ABEPI2 [N-tert-butyl-2-(1-tert-butyltetrazol-5-yl)sulfanylacetamide], were shown to lead to minocycline accumulation within A. baumannii during serum growth and inhibit the efflux potential of the organism. While both compounds also inhibited the antibiotic efflux properties of the bacterial pathogen Pseudomonas aeruginosa, they did not display significant cytotoxicity toward human cells or mammalian Ca(2+) channel inhibitory effects, suggesting that ABEPI1 and ABEPI2 represent promising structural scaffolds for the development of new classes of bacterial antibiotic efflux pump inhibitors that can be used to potentiate the activities of current and future antibiotics for the therapeutic intervention of Gram-negative bacterial infections.

Topics: Acetamides; Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Biological Transport; Calcium Channels; Cell Line; Ciprofloxacin; Drug Resistance, Multiple, Bacterial; HEK293 Cells; Humans; Membrane Transport Proteins; Meropenem; Microbial Sensitivity Tests; Minocycline; Pseudomonas aeruginosa; Sulfonamides; Tetracycline; Tetrazoles; Thienamycins; Tigecycline

Clinical information on tigecycline use in serious nosocomial infections is limited, and the efficacy is uncertain. The aim of this retrospective study was to assess the utilization pattern and the effectiveness of tigecycline in a tertiary medical center in Taiwan.. A retrospective study of the clinical and microbiological outcome of all patients treated with tigecycline for at least 72 hours over a 2-year period was conducted in a 730-bed teaching hospital.. Data from 133 patients with 149 cases of nosocomial infection were analyzed in this assessment. The mean APACHE II score at the initiation of tigecycline therapy was 22.5 ± 8.8, and the mean duration of treatment was 11.4 ± 5.6 days. Pneumonia was the most frequently diagnosed clinical indication for tigecycline use (113 cases, 76%). An overall positive clinical outcome was observed in 75 cases (50%). Multidrug-resistant Acinetobacter baumannii (MDRAB) is the most common organism for tigecycline therapy (n = 59), with a positive clinical outcome of 38% in tigecycline monotherapy, 66% in dualtherapy, and 17% in triple-therapy (p = 0.031). The most commonly used combining agents with tigecycline to treat MDRAB infections were intravenous colistin, inhaled colistin, and cepoferazone/sulbactam, with positive clinical outcome rates of 53%, 100%, and 80%, respectively. Admission to intensive care unit was identified as a predictive factor for negative clinical outcome.. Our pneumonia-dominated study population demonstrated a lower clinical improvement rate of tigecycline compared to previous published data. Tigecycline monotherapy is not recommended for MDRAB infection, but colistin or cephoperazone/ sulbactam combined with tigecycline seemed to yield a good clinical outcome for MDRAB infection.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cross Infection; Drug Resistance, Bacterial; Female; Humans; Male; Middle Aged; Minocycline; Retrospective Studies; Tigecycline

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Humans; Minocycline

Among Acinetobacter species, A. baumannii and other closely related species are commonly implicated in nosocomial infections. These organisms are usually multidrug resistant (MDR), and therapeutic options to treat A. baumannii infections are very limited. Clinicians have been resorting to older antimicrobial agents to treat infections caused by MDR A. baumannii, and some of these agents have documented toxicity and/or are not optimized for the infection type to be treated. Recent clinical experience supported by antimicrobial susceptibility data suggests that minocycline has greater activity than other tetracyclines and glycylcyclines against various MDR pathogens that have limited therapeutic options available, including Acinetobacter species. An intravenous formulation of minocycline has recently become available for clinical use, and in contrast to most older tetracyclines, minocycline has high activity against Acinetobacter species. In this report, we summarized some of the characteristics of the tetracycline class, and quantified the minocycline activity against contemporary (2007-2011) isolates and its potential therapeutic role against a collection of 5477 A. baumannii and other relevant gram-negative organisms when compared directly with tetracycline, doxycycline, and other broad-spectrum antimicrobial agents. Acinetobacter baumannii strains were highly resistant to all agents tested, with the exception of minocycline (79.1% susceptible) and colistin (98.8% susceptible). Minocycline (minimum inhibitory concentration that inhibits 50% and 90% of the isolates [MIC(50/90)]: 1/8 µg/mL) displayed greater activity than doxycycline (MIC(50/90): 2/>8 µg/mL) and tetracycline hydrochloride (HCL) (only 30.2% susceptible) against A. baumannii isolates, and was significantly more active than other tetracyclines against Burkholderia cepacia, Escherichia coli, Serratia marcescens, and Stenotrophomonas maltophilia isolates. In vitro susceptibility testing using tetracycline HCL as a surrogate for the susceptibility other tetracyclines fails to detect minocycline-susceptible isolates and the potential utility of minocycline for the treatment of many MDR A. baumannii infections and other difficult-to-treat species, where there are often limited choices of antimicrobials.

Topics: Acinetobacter; Acinetobacter Infections; Anti-Bacterial Agents; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Microbial Sensitivity Tests; Minocycline

Minocycline is an "old-drug" with Food and Drug Administration approval for the treatment of infection due to Acinetobacter species. The purpose of this study is to describe an Antimicrobial Stewardship Program's evaluation of minocycline for the treatment of patients with multidrug resistant A. baumannii (MDR-AB) infections.. This study evaluated hospitalized adult patients (September 2010 through March 2013) who received minocycline intravenously (IV) for a MDR-AB infection. Clinical and microbiological outcomes were analyzed. Secondary outcomes included infection-related mortality, length of hospital stay (LOS), infection-related LOS, intensive care unit (ICU) LOS, mechanical ventilation days, and 30-day readmission.. A total of 55 patients received minocycline. Median age was 56 (23-85) years, 65% were male with an APACHE II score of 21 (4-41). Clinical success was achieved in 40/55 (73%) patients treated with minocycline monotherapy (n = 3) or in combination with a second active agent (n = 52). Overall 43 (78%) patients demonstrated documented or presumed microbiologic eradication. Infection-related mortality was 25%. Hospital LOS was 31 (5-132) and infection-related LOS was 16 (2-43) days. Forty-seven (85%) patients were admitted to the ICU for a LOS of 18 (2-78) days. Thirty-nine (71%) patients required mechanical ventilation for 6 (2-29) days. One patient had a 30-day readmission.. The response rate to minocycline monotherapy or in combination for the treatment of MDR-AB infections is encouraging as therapeutic options are limited. Prospective studies in patients with MDR-AB infections will help establish the role of minocycline alone or in combination with other antimicrobials.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Minocycline; Retrospective Studies; Treatment Failure; Young Adult

This study reports the results of antimicrobial susceptibility testing of 10 MDR and 74 XDR Acinetobacter bauman- nii clinical isolates from our hospital routine. We used three different methods: two automated systems (Sensititre and VITEK 2) and one standardized manual method (E-test). Since many published papers refer to in vitro tests performed by E-test, the aim of this study was to test if this method is reliable for testing tigecycline. The results obtained show that E-test significantly overestimates the MIC of the broth microdilution (reference test), thus ob- taining a significant number of major errors (resistant instead of sensitive). VITEK 2 also shows the same problem, but it is less critical. We therefore conclude that these methods do not seem to be very reliable in the performance of susceptibility testing of MDR and XDR Acinetobacter baumannii against tigecycline.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

Acinetobacter baumannii has become a serious concern in clinical practice owing to its multiple resistance to antimicrobial agents. Tigecycline and colistin may be used as alternative therapies, although they lack practical susceptibility testing guidelines. This study assessed the reliability of commonly used methods (disc diffusion, Etest and VITEK(®) 2) for testing sensitivity to both agents compared with the reference broth microdilution (BMD) method against 290 A. baumannii clinical isolates, including multidrug-resistant isolates. For tigecycline, essential agreement and categorical agreement (CA) of minimum inhibitory concentration (MIC) testing were most correlated with BMD when using a breakpoint of susceptible (S)≤1/resistant (R)>2 mg/L; 94.8% and 84.5% (Etest) and 99.3% and 75.5% (VITEK 2), respectively. A disc diffusion zone diameter breakpoint of S≥17/R≤12 mm showed good agreement. All three methods did not show major errors or very major errors. For colistin, a BMD MIC breakpoint of S≤2/R>4 mg/L was proposed. The disc diffusion method was highly reproducible with a zone diameter breakpoint of S≥12/R≤9 mm. However, Etest results showed a different MIC range, and the MIC breakpoint should be modified to S≤0.5/R>2 mg/L, whilst a similar MIC breakpoint to BMD could be applied for VITEK 2. Both Etest and VITEK 2 showed a high CA for isolates with colistin-susceptible and -resistant results. We recommend that disc diffusion, Etest and VITEK 2 may be used with caution for testing tigecycline and colistin based on our proposed breakpoints. The reliability of individual methods will be discussed.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Reproducibility of Results; Tigecycline

Tigecycline (TG) has been shown to be active in vitro against Acinetobacter baumannii, although data on the clinical efficacy of TG alone or in combination for the treatment of infections due to multidrug-resistant A. baumannii (MDRAB) remain limited. The purpose of this study was to investigate the clinical outcomes of patients with healthcare-associated infections (HAIs) caused by MDRAB who were treated with imipenem/cilastatin and sulbactam, and TG alone or in combination with other antibiotics. A total of 386 patients with HAIs caused by MDRAB were retrospectively analyzed and grouped into TG and non-TG groups, depending on whether they received TG treatment. Of the 266 patients in the TG group, 108 were treated with TG alone and 158 were treated with TG in combination with ceftazidime, ceftriaxone, piperacillin/tazobactam, or a carbapenem. All 120 patients in the non-TG group were treated with imipenem/cilastatin and sulbactam. The primary outcome measure was 30-day mortality after TG treatment and the secondary outcome was clinical outcome. There were no significant differences in survival rates between the two groups. However, the rate of unfavorable outcome was significantly lower (p < 0.05) among patients in the TG group than among patients in the non-TG group. The most significant predictor of unfavorable outcome was sepsis, whereas TG treatment and microbial eradication were the most significant predictors of favorable outcomes. Our study represents the largest study of patients with MDRAB infection treated with TG and expands our understanding of the role of TG therapy alone or in combination with other agents for the treatment of HAI caused by MDRAB.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Ceftazidime; Ceftriaxone; Cilastatin; Cross Infection; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Imipenem; Male; Minocycline; Piperacillin; Sulbactam; Tigecycline; Treatment Outcome

The aim of this study was to evaluate the in vitro activity of doripenem (DOR) alone and in combination with a variety of commonly used anti-Acinetobacter chemotherapeutic agents against 22 primary multidrug-resistant (MDR) Acinetobacter baumannii isolates (including 17 isolates that were resistant to DOR) from Intensive Care Unit patients. Antibiotic interactions were evaluated using the chequerboard method and the time-kill assay.. Considering all antimicrobials in combination with DOR, chequerboard analysis showed synergy in 13 A. baumannii strains (54.2%). Seven strains (29.2%) showed ≥2 synergistic interactions. DOR showed synergy in combination with tigecycline (TIG) (eight strains), colistin (COL) (eight strains), amikacin (AMK) (four strains), ampicillin/sulbactam (two strains), and rifampicin (one strain). Remarkably, synergistic effects were detected only in DOR nonsusceptible strains. Time-kill assays confirmed synergy in eight isolates (giving 10 synergistic interactions) for DOR in combination with TIG (n=4), COL (n=5), and AMK (n=1). No antagonistic interactions were observed with both methods.. This study demonstrates the in vitro synergistic activity of DOR in combination with TIG, COL, and AMK against DOR-resistant A. baumannii strains, opening the way to in vivo assessment of novel combination therapies for treatment of infections caused by MDR A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Amikacin; Anti-Bacterial Agents; Carbapenems; Colistin; Doripenem; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Humans; Intensive Care Units; Microbial Sensitivity Tests; Minocycline; Tertiary Healthcare; Tigecycline

Acinetobacter baumannii is an important emerging pathogen in health care-acquired infections and is responsible for severe nosocomial and community-acquired pneumonia. Currently available mouse models of A. baumannii pneumonia show poor colonization with little to no extrapulmonary dissemination. Here, we describe a mouse model of A. baumannii pneumonia using a clinical isolate (LAC-4 strain) that reliably reproduces the most relevant features of human pulmonary A. baumannii infection and pathology. Using this model, we have shown that LAC-4 infection induced rapid bacterial replication in the lungs, significant extrapulmonary dissemination, and severe bacteremia by 24 h postintranasal inoculation. Infected mice showed severe bronchopneumonia and dilatation and inflammatory cell infiltration in the perivascular space. More significantly, 100% of C57BL/6 and BALB/c mice succumbed to 10(8) CFU of LAC-4 inoculation within 48 h. When this model was used to assess the efficacy of antimicrobials, all mice treated with imipenem and tigecycline survived a lethal intranasal challenge, with minimal clinical signs and body weight loss. Moreover, intranasal immunization of mice with formalin-fixed LAC-4 protected 40% of mice from a lethal (100× 100% lethal dose) intraperitoneal challenge. Thus, this model offers a reproducible acute course of A. baumannii pneumonia without requiring additional manipulation of host immune status, which will facilitate the development of therapeutic agents and vaccines against A. baumannii pneumonia in humans.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacteremia; Bacterial Vaccines; Body Weight; Bronchopneumonia; Disease Models, Animal; Female; Imipenem; Immunization; Lung; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Microbial Sensitivity Tests; Minocycline; Pneumonia, Bacterial; Reproducibility of Results; Tigecycline; Time Factors

Multidrug resistance is common among Acinetobacter baumannii, limiting the available options used to treat infections caused by this organism. The objective of this study was to compare monotherapy and combination therapy with ampicillin/sulbactam, doripenem and tigecycline against multidrug-resistant A. baumannii using an in vitro pharmacodynamic model.. Human free-drug concentration profiles of clinically relevant ampicillin/sulbactam, doripenem and tigecycline were simulated alone and in two-drug combinations against four clinical A. baumannii isolates (MICs: ampicillin/sulbactam, 4/2-64/32 mg/L; doripenem, 16 to ≥64 mg/L; and tigecycline, 1-4 mg/L) over 24 h. Microbiological response was measured as log10 cfu/mL and the area under the bactericidal curve (AUBC).. Control strains grew to 7.11 ± 0.13 log10 cfu/mL. Except for ampicillin/sulbactam-containing regimens against the single ampicillin/sulbactam-susceptible isolate, all A. baumannii demonstrated regrowth to 24 h control levels against all mono and combination regimens. Using AUBC as an endpoint, the most active regimens were 9 g of ampicillin/sulbactam every 8 h (3 h infusion) + 2 g of doripenem every 8 h (4 h infusion; 87.8 ± 21.0), 9 g of ampicillin/sulbactam every 8 h (3 h infusion) + 200 mg of tigecycline every 12 h (30 min infusion; 100.6 ± 33.0) and 9 g of ampicillin/sulbactam every 8 h (3 h infusion) monotherapy (116.7 ± 31.6), followed by 3 g of ampicillin/sulbactam every 6 h (30 min infusion) + 200 mg of tigecycline every 12 h (30 min infusion; 134.0 ± 31.5) and 2 g of doripenem every 8 h (4 h infusion) + 200 mg of tigecycline every 12 h (30 min infusion; 142.7 ± 16.9).. Although specific combination regimens displayed additive activity at aggressive doses against these multidrug-resistant A. baumannii, none of the regimens could maintain cfu reductions against the more resistant isolates.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Ampicillin; Anti-Bacterial Agents; Bacterial Load; Carbapenems; Doripenem; Drug Combinations; Drug Resistance, Multiple, Bacterial; Humans; In Vitro Techniques; Minocycline; Models, Theoretical; Sulbactam; Tigecycline

Multidrug-resistant Acinetobacter baumannii infections are serious challenges for clinicians because of A. baumannii propensity to acquire resistance to a wide spectrum of antimicrobial agents. In this study, 91 A. baumannii isolates from patients in tertiary intensive care units of three university hospitals in the north, central, and south of Iran were selected and tested for susceptibility to 22 antimicrobials; amplified restriction fragment polymorphism and multiplex polymerase chain reaction methods were used to determine genetic relationships and International Clone (IC) of A. baumannii isolates, respectively. Twenty-four genotypes were identified in A. baumannii isolates. About 91.2% of isolates categorized into 4 distinct clusters; one was more heterogeneous and observed across the three locations. A considerable number of the isolates (27.5%) belonged to the novel IC variant, sequence group 7 (SG7), which was geographically widespread in three locations. The drug resistance pattern showed that 14.2%, 20%, and 77% of the A. baumannii isolates were resistant to colistin, tigecycline, and rifampicin, respectively. Nine percent of isolates (8) showed simultaneous resistance to colistin, rifampicin, and tigecycline. Interestingly, all of them were susceptible to ampicillin-sulbactam and/or tobramycin. According to our results, SG7 could be considered as a pan-Iranian clone.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Ampicillin; Anti-Bacterial Agents; Bacterial Typing Techniques; Clone Cells; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Intensive Care Units; Iran; Microbial Sensitivity Tests; Minocycline; Multiplex Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Prevalence; Rifampin; Sulbactam; Tertiary Healthcare; Tigecycline; Tobramycin

A carbapenem-resistant Acinetobacter baumannii strain was isolated from the peritoneal fluid of a patient with complicated intra-abdominal infection and evaluated at the Multidrug-resistant Organism Repository and Surveillance Network by whole-genome sequencing and real-time PCR. The isolate was sequence type 25 and susceptible to colistin and minocycline, with low MICs of tigecycline. blaNDM-1 was located on a plasmid with >99% homology to pNDM-BJ02. The isolate carried numerous other antibiotic resistance genes, including the 16S methylase gene, armA.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; beta-Lactamases; Colistin; Drug Resistance, Multiple, Bacterial; High-Throughput Nucleotide Sequencing; Honduras; Humans; Male; Methyltransferases; Minocycline; Peritonitis; Plasmids; Tigecycline

The lack of active antimicrobial agents against multidrug-resistant (MDR) Acinetobacter baumannii has posed great threat to the public health. Combination therapies with antibiotics owning different antimicrobial mechanisms have been proposed as good options for treating MDR A. baumannii infections. This study was aimed to investigate the in vitro effects of tigecycline in combination with colistin and sulbactam against MDR A. baumannii. A total of 70 strains from two hospitals in China were examined in the study. The checkerboard method was used for determining synergistic activity of different antibiotic combinations. Tigecycline/colistin combination displayed synergistic and partial synergistic activity in 24.3% of the isolates, whereas the tigecycline/sulbactam combination showed synergistic and partial synergistic activity in 64.3% of the isolates. Neither of the combinations showed antagonism in this study. In addition, for evaluating the ability of combinations on resistance prevention, mutant prevention concentrations (MPCs) of tigecycline, colistin, sulbactam alone and tigecycline in combination with colistin and sulbactam were studied against MDR A. baumannii. Compared with tigecycline used alone, combination therapies could achieve lower MPCs of tigecycline. However, when the MPCs of dual-drug therapy were in conjunction with clinical pharmacokinetic profiles, combinations may not strictly curb the occurrence of resistance at current dosage regimen. In summary, this study suggested that combination therapy was a good option for treating MDR A. baumannii infections. But the finding that combination with these drugs at current dosage regimen may not prevent emergence of resistance warranted further studies on dosage of combined antibiotics required for achieving resistance prevention.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; China; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Minocycline; Sulbactam; Tigecycline

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Drug Resistance, Bacterial; Female; Humans; Minocycline; Pneumonia, Bacterial; Tigecycline; Treatment Outcome

Nosocomial infection caused by carbapenem-resistant Acinetobacter baumannii is a worldwide problem and treatment options remain controversial. This study investigated the in vitro effect of various antibiotic combinations against carbapenem-resistant A. baumannii strains.. Antibiotic susceptibility of A. baumannii strains was analysed. In vitro synergistic efficacy of colistin combined with tigecycline, cefoperazone/sulbactam or piperacillin/tazobactam was tested against carbapenem-resistant A. baumannii strains. Synergy studies were performed using an eplisometer test-strip method.. Of the 50 carbapenem-resistant A. baumannii strains tested, 96% were susceptible to colistin and 64% were susceptible to tigecycline. Colistin-tigecycline, colistin-cefoperazone/sulbactam and colistin-piperacillin/tazobactam combinations were found to have synergistic effects against six (12%), two (4%), and one (2%), respectively, of the strains tested.. Colistin combined with tigecycline, cefoperazone/sulbactam or piperacillin/tazobactam revealed synergistic effects in some carbapenem-resistant A. baumannii strains. These results, together with the shortage of treatment options and the risk of developing resistance to colistin, suggest that clinicians should use colistin combined with other antibiotics or β-lactamase inhibitors when treating carbapenem-resistant A. baumannii infection.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamase Inhibitors; Carbapenems; Cefoperazone; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Microbial Sensitivity Tests; Minocycline; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sulbactam; Tigecycline

The management of infections due to A. baumannii is difficult because of rapidly developing resistance, however, tigecycline, a glycylcycline antimicrobial, is in use for several years. In the present study, it was aimed to determine the susceptibility rates of A. baumannii to tigecycline. A total of 90 A. baumanni isolates were tested using three methods such as disk diffusion, broth microdilution, and E-test. The MIC50 and MIC90 values and the MIC range were found as 2 µg/ml, 4 µg/ml, and 0.1-8 µg/ml by microdilution; and 2 µg/ml, 6 µg/ml, and 0.1-12 µg/ml by E-test, respectively. There were a few major errors as well as the minor rates were all high as between 35.7%-46.7%. The accuracy rates between the methods were low as 53.3% (48/90) between disk diffusion and E-test, 51.1% (46/90) between disk diffusion and microdilution, and 60.0% (54/90) between E-test and microdilution. In the ROC curve analysis, an inhibition zone diameter of susceptibility breakpoint of 21.5 mm had sensitivity between 68.8%-88.9%; specificity between 81.9%-87.9%; and accuracy between 80.0%-83.33%. An analysis based on EUCAST's non-species breakpoints, the MIC tests showed higher accuracy with a rate of 96.7%, however, performance of disk diffusion got worse as lower than 25%. In conclusion, we showed that the reliability of the methods even did not remain as high as the past. Our study presented that none of three methods revealed reliable results in determination of susceptibility of A. baumanni to tigecycline, so the clinical response should be followed up carefully in such cases.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cross Infection; Disk Diffusion Antimicrobial Tests; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Reproducibility of Results; Tigecycline

The present study aimed to evaluate antimicrobial activity of tigecydcline against 84 multidrug resistant (MDR) Acinetobacter spp. strains by disc diffusion and E-test methods. The results of disc diffusion test were compared according to two different interpretation ways. In addition, E-test results and the disc diffusion results that interpreted by both the methods were checked for compatibility. According to the disc diffusion test, 3 strains (3.57%) were found resistant to tigecycline when considering breakpoints suggested by Food and Drug Administration (FDA). On the other hand, none of the strains was found resistant to the evaluation criteria recommended by Jones etal. (2007). Considering E-test results of tigecycline, MIC, and MICG, values of tigecycline for Acinetobacter spp. were 0.75 and 1 mg/l, respectively. Based on FDA defined breakpoints for Enterobacteriaceae, any resistant isolate was detected. In conclusion, although there are some differences in the results, tigecycline was found quite effective on Acinetobacter spp. isolates with reference to the both disc diffusion and the E-test methods.

Topics: Acinetobacter; Acinetobacter Infections; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Genotype; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline; Turkey

In recent years, multidrug-resistant Acinetobacter baumannii has been reported as an important nosocomial pathogen, and treatment options are limited. The aim of this study was to investigate the additional effect of sulbactam on monotherapy with colistin, tigecycline and imipenem in experimental sepsis with carbapenem-resistant A. baumannii in mice.. Sepsis was developed in 8- to 10-week-old BALB/c mice by an intraperitoneal injection of A. baumannii. Antibiotic was given intraperitoneally 2 h after bacterial inoculation. Each experimental group had 15 mice and was divided into 3 subgroups. Mice were sacrificed at 24, 48 or 72 h. Lung, liver, heart and spleen samples were cultured, and homogenates of lung and liver were used to detect the number of colony-forming units per gram. Bacterial clearance was compared in lung and liver at different time points.. Imipenem did not decrease the bacterial load, but the other antibiotics showed significant bactericidal activity compared with the control group, and the combination of imipenem with sulbactam decreased the bacterial load in lung and liver. However, the addition of sulbactam to colistin and tigecycline had no significant effect on bacterial counts. Only the addition of sulbactam to imipenem showed better bactericidal activity compared to imipenem alone.. These results suggested that combining sulbactam with tigeycline or colistin does not increase the efficiency of these antibiotics.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacterial Load; Carbapenems; Colistin; Disease Models, Animal; Drug Resistance, Bacterial; Drug Therapy, Combination; Humans; Imipenem; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Minocycline; Sepsis; Sulbactam; Tigecycline; Time Factors

Although tigecycline is considered one of the few therapeutic options for carbapenem-resistant Acinetobacter baumannii (CRAB) bacteraemia, its role in the treatment of CRAB bacteraemia remains unclear. We describe the clinical outcomes of 9 patients who received tigecycline for CRAB bacteraemia. Although all CRAB blood isolates were susceptible to tigecycline, 5 (56%) deaths were related to CRAB bacteraemia and 1 case of breakthrough CRAB bacteraemia was observed during tigecycline therapy. Clinical outcomes of tigecycline therapy may be poor in patients with tigecycline-susceptible CRAB bacteraemia, although multiple factors including delayed treatment could contribute to the poor outcomes.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; Cohort Studies; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Tigecycline; Treatment Outcome

Resistance to minocycline has emerged in multidrug-resistant Acinetobacter baumannii isolates from Buenos Aires hospitals. Few reports about the description and dispersion of tet genes in this species have been published. We observed the presence of tet(B) in all minocycline-resistant isolates. This gene was found to be associated with the ISCR2 mobile element, which may, in part, explain its dispersion.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Argentina; Base Sequence; Humans; Microbial Sensitivity Tests; Minocycline; Molecular Sequence Data; Plasmids; Retroelements; Sequence Analysis, DNA; Tetracycline Resistance

Acinetobacter species are well-known causes of health care-associated infections. The longitudinal epidemiology of this species in the hospital setting is poorly understood. A sudden, persistent increase in multidrug-resistant (MDR) A baumannii infections occurred beginning in June 2006 at Temple University Hospital in Philadelphia. An analysis was done to describe the longitudinal molecular epidemiology of MDR A baumannii in a tertiary care hospital.. This was an epidemiologic investigation using repetitive extragenic palindromic-PCR (rep-PCR) of patients with a positive culture for MDR A baumannii admitted to the hospital between February 2006 and January 2010. MDR A baumannii were defined as susceptible only to colistin and/or tigecycline.. The incidence rate of MDR A baumannii rose from 0.36 cases per 1,000 patient-days (pre-epidemic) to 0.86 cases per 1,000 patient-days, due mainly to an increase in the surgical intensive care unit. Enhanced infection control measures were implemented, but waves of MDR A baumannii continued to be documented through routine surveillance. Of 32 strains collected in 2006-2007, a single predominant clone and 2 minor clones accounted for almost all of the cases of MDR A baumannii studied. Of 24 strains collected in 2008-2009, another clone, different from those studied in the earlier period, predominated, and was accompanied by 3 minor variants.. Following an outbreak in the surgical intensive care unit, MDR A baumannii persisted in our institution for a 3-year period despite rigorous infection control measures. An unexpected strain replacement occurred during this period, with the original predominant strain disappearing completely and new minor clones displacing the original minor clones.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Typing Techniques; Colistin; Cross Infection; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Hospitals; Humans; Incidence; Intensive Care Units; Longitudinal Studies; Minocycline; Philadelphia; Polymerase Chain Reaction; Tigecycline

The emergence of colistin or tigecycline resistance as well as imipenem resistance in Acinetobacter baumannii poses a great therapeutic challenge. The bactericidal and synergistic effects of several combinations of antimicrobial agents against imipenem-, colistin- or tigecycline-resistant A. baumannii isolates were investigated by in vitro time-kill experiments. Six imipenem-resistant A. baumannii blood isolates were examined in this study, including colistin- and tigecycline-susceptible, colistin-resistant but tigecycline-susceptible, and colistin-susceptible but tigecycline-resistant isolates. Time-kill studies were performed using five antimicrobial agents singly or in combinations (imipenem plus colistin, imipenem plus ampicillin-sulbactam, colistin plus rifampicin, colistin plus tigecycline, and tigecycline plus rifampicin) at concentrations of 0.5× and 1× their MICs. Only imipenem was consistently effective as a single agent against all six A. baumannii isolates. Although the effectiveness of combinations of 0.5× MIC antimicrobial agents was inconsistent, combination regimens using 1× MIC of the antimicrobial agents displayed excellent bactericidal activities against all six A. baumannii isolates. Among the combinations of 0.5× MIC antimicrobial agents, the combination of colistin and tigecycline showed synergistic or bactericidal effects against four of the isolates. This in vitro time-kill analysis suggests that antimicrobial combinations are effective for killing imipenem-resistant A. baumannii isolates, even if they are simultaneously resistant to either colistin or tigecycline. However, the finding that the combinations of 0.5× MIC antimicrobial agents were effective on only some isolates may warrant further investigation of the doses of combination agents needed to kill resistant A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; Blood; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Imipenem; Microbial Sensitivity Tests; Microbial Viability; Minocycline; Tigecycline; Time Factors

This study was conducted to investigate the molecular epidemiology and antimicrobial susceptibility of multidrug-resistant (MDR) Acinetobacter baumannii to three types of antibiotics.. One hundred and thirty-four specimens of MDR A baumannii were collected from three branches (Taipei, Dalin, and Hualien branches) of Buddhist Tzu Chi Hospital, which are located in northern, southern, and eastern Taiwan, during 2007. Genotyping was performed by pulsed-field gel electrophoresis. Antibiotic susceptibilities to colistin, rifampicin, and tigecycline were determined. The synergistic effects of rifampin and colistin were also evaluated.. Antibiotic susceptibility testing showed that 10.4%, 47.8% and 45.5% of the MDR A baumannii isolates are resistant to colistin, rifampicin, and tigecycline, respectively. A majority of the rifampicin-resistant isolates (62.7%) were found in the Haulien branch, whereas 62.2% of tigecycline-resistant isolates were found in the Taipei branch. The combination of colistin and rifampicin had a synergistic effect on all of the isolates. Genotyping by pulsed-field gel electrophoresis identified 17, 23, and 11 pulsotypes in the Taipei, Dalin, and Haulien branches, respectively. Furthermore, 74.5% of isolates in the Haulien branch were identified as one of three pulsotypes. Among 37 rifampicin-resistant and 22 tigecycline-resistant MDR A baumannii isolates found in the Haulien branch, 51.3% (19/37) and 50% (11/22) of the isolates belonged to the same clone, respectively.. This study confirms the high prevalence of resistance to rifampicin and tigecycline in MDR A baumannii in the three hospitals that were studied, and the high proportion of identical strains that exist in eastern Taiwan.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cluster Analysis; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Electrophoresis, Gel, Pulsed-Field; Genotype; Humans; Microbial Sensitivity Tests; Minocycline; Molecular Epidemiology; Molecular Typing; Prevalence; Rifampin; Taiwan; Tigecycline

The Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) began in 2004 to monitor global antimicrobial susceptibility to tigecycline and a range of comparator antimicrobials among gram-positive and gram-negative organisms.. The aim of this study was to report changes in MIC for tigecycline and other antimicrobial agents among 10,149 Acinetobacter baumannii isolates collected globally between 2004 and 2009.. MICs of 10,149 isolates were determined locally using Clinical Laboratory and Standards Institute (CLSI) methodologies. Antimicrobial susceptibility was ascertained according to CLSI interpretive criteria (no interpretive criteria have been approved for tigecycline against Acinetobacter spp).. Increases in resistance were noted for most antimicrobial agents in all regions. Significant (P < 0.05) increases in percentage resistance were reported for all antimicrobial agents globally. The smallest changes in cumulative geometric mean MICs were reported for tigecycline (0.2 mg/L) and cefepime (3.5 mg/L). MIC(90)s were at the top of their testing ranges for most agents against both multidrug-resistant (MDR) and non-MDR isolates; only tigecycline showed little change in MIC(90) between MDR (2 mg/L) and non-MDR (1 mg/L) isolates. Resistance was higher among isolates from the intensive care unit (ICU) compared with non-ICU isolates.. These findings suggest that resistance is increasing among clinical isolates of A baumannii globally. Although resistance to tigecycline has been reported in the treatment of infections caused by A baumannii, it retains in vitro activity against this pathogen.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Africa; Anti-Bacterial Agents; Asia; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Europe; Humans; Intensive Care Units; Latin America; Microbial Sensitivity Tests; Middle East; Minocycline; North America; Tigecycline; Time Factors

Therapeutic options are limited for infections because of Acinetobacter baumannii and carbapenem-resistant Enterobacteriaceae (CRE). Study aim was to compare the efficacy of colistin to tigecycline for the treatment of these types of infections.. A retrospective study was conducted at the Detroit Medical Center. Adult patients with infections because of A baumannii or CRE in 2009 who received ≥2 doses of colistin or tigecycline were studied. Risk factors, outcomes, and costs were analyzed.. There were 82 patients with infections because of A baumannii, 12 with CRE, and 12 with A baumannii and CRE coinfection. Seventy-one patients received colistin, 16 received tigecycline, and 19 received both colistin and tigecycline. Seven isolates were nonsusceptible to colistin and 79 to tigecycline. Patients receiving colistin alone or in combination were more likely to die during their hospitalization than patients receiving only tigecycline (P = .002). However, patients receiving colistin had higher severity of acute illness and had notable delays in initiation of effective antimicrobial therapy (P < .001).. Compared with patients who received tigecycline alone, patients who received colistin alone or in combination had a higher severity of acute illness indices and delays in initiation of effective therapy. This increased severity of illness contributed to the increased rate of mortality among patients treated with colistin for A baumannii or CRE infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenems; Case-Control Studies; Cohort Studies; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Male; Michigan; Middle Aged; Minocycline; Retrospective Studies; Severity of Illness Index; Survival Analysis; Tigecycline; Treatment Outcome

The In vitro susceptibility of clinical and environmental isolates of Acinetobacter baumannii to tigecycline and other antibiotics was determined by disk diffusion method. The E-test was used to determine the minimum inhibitory concentration (MIC). The growth curves of tigecycline treated environmental and clinical strains were established. Fifty-seven percent and 75% of the clinical and environmental isolates were MDR strains, respectively. Ninety-five percent of the clinical isolates were susceptible to tigecycline and 5% showed intermediate resistance with MIC ranging between 0.032 and 3 mg/l. Tigecycline susceptible and intermediate resistance among the environmental isolates were 40% and 60%, respectively, with a significantly lower MIC range of 0.5-4 mg/l. The bacterial growth curves demonstrated the higher ability of the environmental strains to tolerate the antibiotic effects than the clinical strains. The relatively high resistance profile among the environmental isolate suggests an insidious emergence of tigecycline resistance amongst A. baumannii. Strict infection control procedures are imperative to prevent the dissemination of tigecycline-resistant A. baumannii strains in the hospital environment.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Drug Resistance, Bacterial; Hospitals, Teaching; Humans; In Vitro Techniques; Malaysia; Microbial Sensitivity Tests; Minocycline; Tigecycline

To investigate the clinical and microbiological effectivity of intravitreal tigecycline in an experimental rabbit endophthalmitis model caused by imipenem resistant Acinetobacter baumannii.. Forty-eight eyes of 24 New Zealand white albino rabbits were divided into six groups (n=8 in each). The right eyes were divided into three groups and defined as infected group; left eyes were divided into three groups and defined as uninfected group. Infected group received 0.1 ml intravitreal A. baumannii suspension. Twenty-four hours after bacterial inoculation, group 1 received 1 mg/0.1 ml tigecycline and group 2 received 0.5 mg/0.1 ml tigecycline. Group 3 eyes received no treatment. In group 4, 0.1 ml of saline solution was injected. Groups 5 and 6 were received intravitreal tigecycline injection of 1 mg/0.1 ml and 0.5 mg/0.1 ml respectively. The eyes were enucleated for histopathological evaluation on the sixth day. Clinical and histological scoring systems were used to evaluate clinical and histological severity of the intraocular infection.. The mean clinical scores of the six groups at the sixth day were 11±1.92, 12.4±6.2, 8.5±2.7, 0, 3±1.3, and 3±1.4 respectively. Mean histopathological scores were 7.8±2.8, 7.0±1.5, 5.6±1.4, 0, 0, and 0 respectively. There was no significant difference in mean clinical and histopathological scores of infected group (groups 1, 2 and 3). There was significant difference in mean clinical scores of groups 5 and 6 compared with group 4. Groups 4, 5 and 6 showed normal histological structure in histopathological evaluation and showed no significant difference. Microbiological cure was achieved in all infected eyes.. Experimental rabbit endophthalmitis model caused by imipenem resistant A. baumannii was microbiologically cured by intravitreal tigecycline injection. However, a hypersensitivity-like reaction due to intravitreal application of tigecycline limits the use of this antimicrobial agent in A. baumannii endophthalmitis.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Disease Models, Animal; Endophthalmitis; Eye Infections, Bacterial; Female; Humans; Intravitreal Injections; Male; Minocycline; Rabbits; Tigecycline; Treatment Outcome

We investigated the clinical characteristics and outcomes of 43 patients with Acinetobacter junii bacteremia at a 2,500-bed tertiary care center in northern Taiwan. These organisms were confirmed to the species level by an array assay and 16S rRNA gene sequence analysis. The antimicrobial susceptibilities of the 43 A. junii isolates to 13 agents were determined using the agar dilution method. Susceptibility testing for tigecycline was determined using the broth microdilution method. Most of the patients were hospital-acquired (n = 36, 83.7 %) or healthcare facility-related infections (n = 6, 13.9 %), and 55.8 % had impaired immunity. Central venous access devices were present in 35 (81.4 %) patients; among the total of 43 patients with A. junii bacteremia, 8 patients were diagnosed as catheter-related bloodstream infection and 19 patients were diagnosed as catheter-associated bloodstream infection. Shock requiring inotropic agents occurred in 2 patients (4.6 %). Most patients developed bacteremia in general wards (n = 36, 83.7 %). The overall in-hospital mortality rate was low (7 %), despite the low rate of removal of central venous devices, low rate of holding usage of original central venous devices, and high rate of inappropriate antimicrobial regimens. Carbapenems, fluoroquinolones, and amikacin had potent activity (>95 % susceptible rate) against A. junii isolates. Interestingly, 35 % of the A. junii isolates were resistant to colistin. Tigecycline exhibited low minimum inhibitory concentration (MIC) values (range, 0.06-2 μg/ml, MIC(90), 1 μg/ml) against the A. junii isolates.

Topics: Acinetobacter; Acinetobacter Infections; Adult; Aged; Amikacin; Anti-Bacterial Agents; Bacteremia; Carbapenems; Catheter-Related Infections; Central Venous Catheters; Colony Count, Microbial; Cross Infection; Drug Resistance, Bacterial; Female; Hospital Mortality; Humans; Incidence; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; RNA, Ribosomal, 16S; Sequence Analysis, RNA; Taiwan; Tertiary Care Centers; Tigecycline

Tigecycline has broad spectrum antimicrobial activity and is approved for complicated intra-abdominal infections, complicated skin and soft tissue infections, and community-acquired pneumonia. There are few data on clinical experience of tigecycline in hospital-acquired pneumonia (HAP) and Acinetobacter spp. infection.. A retrospective study was performed at eight hospitals in Korea from May 2009 to January 2010. Adult patients treated with tigecycline regardless of their source of infection or pathogens were enrolled.. Tigecycline was administered in 108 patients. Pneumonia was the most common infection (43.5%), followed by skin and soft tissue infections (20.4%). Acinetobacter baumannii was isolated from 83 patients (76.9%) accounting for 50.3% of isolated pathogens, showing a resistance rate of 67.5% to carbapenems. Superinfection was identified in 32 patients (29.6%). Pseudomonas aeruginosa was most common microorganism causing superinfection (46.9%). Overall 30-day mortality rate was 52.9%. Thirty-day mortality rate of HAP and Acinetobacter spp. infection was 60.5% and 59.4%, respectively.. Tigecycline can be considered as an alternative therapy in patients with HAP or infections caused by Acinetobacter spp., especially extensively drug-resistant A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenems; Coinfection; Community-Acquired Infections; Female; Humans; Male; Middle Aged; Minocycline; Pseudomonas aeruginosa; Pseudomonas Infections; Republic of Korea; Retrospective Studies; Survival Rate; Tigecycline

Due to increasing drug resistance, available antimicrobial options are limited in the treatment of Acinetobacter baumannii infections. Particularly in cases caused by extensively drug-resistant (XDR) A. baumannii, combination regimens must also be taken into consideration. In this study, the efficacies of tigecycline, colistin and tigecycline/colistin combination on bacterial counts in lung tissue were investigated in a rat pneumonia model. One A. baumannii strain resistant to all antimicrobial agents except tigecycline and colistin was selected for the study. In vivo studies revealed a >3 log reduction in bacterial counts in the tigecycline, colistin and combination groups at 24 h and 48 h compared with the control group. No significant differences were determined between colistin, tigecycline and combination groups (P>0.05). On the other hand, differences between treatment groups and the control group were statistically significant (P=0.01). A greater reduction in bacterial counts was observed at 48 h compared with 24 h in the tigecycline group than in the colistin group (P=0.038 and P=0.139, respectively); the most significant decrease between 24 h and 48 h was observed in the combination group (P=0.014). Despite detection of in vitro synergistic activity in this study, no statistically significant differences were found between colistin, tigecycline and combination treatments in terms of efficacy on bacterial counts in lung tissue. In the treatment of infections with a high mortality rate such as pneumonia caused by XDR A. baumannii, combining tigecycline with colistin during the first 48 h and continuing treatment with one of these agents seems a rational approach.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacterial Load; Colistin; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Lung; Minocycline; Pneumonia, Bacterial; Rats; Rats, Wistar; Tigecycline; Time Factors; Treatment Outcome

Acinetobacter baumannii (A. baumannii) has emerged as a major cause of nosocomial pneumonia and sepsis in seriously ill patients. Multidrug-resistant A. baumannii (MDRAB) is increasing in frequency, and the management of it's infections is consequently difficult. Therefore, tigecycline is considered to be the drug of choice for MDRAB treatment. The aim of our study was to evaluate the microbiological eradication and clinical effectiveness of tigecycline against MDRAB in seriously ill patients, including patients with ventilator-associated pneumonia (VAP).. We conducted a retrospective study including patients with A. baumannii infections who were treated with tigecycline between April 1, 2009 and March 31, 2010. We treated 27 patients with tigecycline for MDRAB infections.. The mean age of patients was 66.2 years, and 20 (74.1%) patients were male. The median length of stay at hospital was 74.6 days. MDRAB was eradicated from the site of infection in 23 cases (85.2%), however, only 17 cases (63.0%) showed positive clinical responses. Overall, an in-hospital mortality rate of 51.9% was observed, and 4 cases of death were attributable to sepsis. The combination therapy showed better clinical and microbial success rates than the monotherapy without significant difference.. We observed the relatively low clinical success rate although the microbial eradication rate was high, probably due to superinfections in VAP and bacteremia. We suggest that clinicians should limit tigecycline monotherapy for MDRAB infection in critically ill patients, until large controlled clinical trials should be conducted.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Minocycline; Retrospective Studies; Tigecycline; Treatment Outcome

The aim of this study was to investigate the in vitro activity of minocycline combined with cefoperazone-sulbactam against carbapenem-resistant Acinetobacter baumannii (CRAB). A total of 53 nonduplicate CRAB were collected from inpatients of intensive care units in three hospitals in China from February 2009 to August 2011. Minimum inhibitory concentrations were determined by the broth microdilution method. The checkerboard method was used to determine whether combinations of the two agents act synergistically. Among the 53 A. baumannii, 64.2% of the isolates were susceptible to amikacin and 69.8% were susceptible to cefoperazone-sulbactam. More than 80% of isolates were resistant to the other agents and no isolates were found resistant to polymyxin B and minocycline. The combination of minocycline and cefoperazone-sulbactam demonstrated synergism in 39 isolates, partial synergism in 11 isolates, and indifference in 3 isolates. No antagonistic interactions were observed. Our study demonstrated that minocycline has good activity against CRAB and the combination of minocycline with cefoperazone-sulbactam had significant synergistic activity against these strains in vitro. The combination of minocycline and cefoperazone-sulbactam may be an alternative option for the treatment of infections caused by CRAB.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cefoperazone; Drug Synergism; Drug Therapy, Combination; Humans; Intensive Care Units; Microbial Sensitivity Tests; Minocycline; Sulbactam

We evaluated the Vitek2, Etest, and MIC Test Strip (MTS) methods of tigecycline susceptibility testing with 241 expanded-spectrum cephalosporin-resistant and/or carbapenem-resistant Enterobacteriaceae and Acinetobacter baumannii clinical isolates by using dry-form broth microdilution (BMD) as the reference method. The MIC(50/90)s were as follows: BMD, 1/4 μg/ml; Vitek2, 4/≥8 μg/ml; Etest, 2/4 μg/ml; MTS, 0.5/2 μg/ml. Vitek2 produced 9.1/21.2% major errors, Etest produced 0.4/0.8% major errors, and MTS produced no major errors but 0.4/3.3% very major errors (FDA/EUCAST breakpoints). Vitek2 tigecycline results require confirmation by BMD or Etest for multidrug-resistant pathogens.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenems; Cephalosporins; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Female; Humans; Male; Minocycline

Acinetobacter baumannii is a Gram-negative bacterium which emerged as a significant nosocomial pathogen worldwide. To investigate the molecular basis of the tigecycline-resistant mechanism, we determined the genome sequences of two multidrug-resistant A. baumannii strains isolated from a patient before and after treatment with tigecycline.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cross Infection; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Genome, Bacterial; Humans; Interspersed Repetitive Sequences; Minocycline; Molecular Sequence Data; Sequence Analysis, DNA; Tigecycline

To explore the effects of cefoperazone-sulbactam (C/S) plus minocycline on extensively drug resistant Acinetobacter baumannii (XDRAB) infections in critically ill patients.. For this prospective and single-center trial, a total of 101 patients with infection due to XDRAB received the primary therapy of C/S plus minocycline. Combined use of imipenem-cilastatin was considered when primary therapy failed.. Among them, 77 patients were evaluated. There were 49 males and 28 females with a mean age of (69±20) years. The Acute Physiology and Chronic Health Evaluation (APACHE) II score was 15±5. Among whom 61 had hospital-acquired pneumonia (n=61), primary bacteremia (n=5), intra-abdominal infection (n=3), skin and soft tissue infection (SSTI) (n=2) and multiple sites infection (n=6). Twenty-three patients had mixed bacterial infections. Combined use of imipenem-cilastatin therapy was administered in 7 patients. The treatment duration was (16±4) days. The outcomes were cure (n=21), marked improvement (n=27), improvement (n=26) and ineffectiveness (n=3). The overall effective rate was 62.3% (48/77) and the microbiological clearance rate 46.8% (36/77). The independent factors of decreased efficacy were underlying co-morbidity of impaired ability for infection control (OR=5.3, P=0.020), prolonged infection (OR=3.8, P=0.029), co-infecting organism (OR=3.5, P=0.032) and septic shock (OR=2.5, P=0.037).. The combined regimen of C/S and minocycline is efficacious in the treatment of infections caused by XDRAB. But it has a lower rate of microbiological eradication.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Aged, 80 and over; Cefoperazone; Cross Infection; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Minocycline; Prospective Studies; Sulbactam

Mediastinitis due to Acinetobacter baumannii is rare.. We report a case of mediastinitis caused by pan-resistant A. baumannii in a patient with multiple comorbidities who underwent cardiopulmonary bypass and we also present a literature review.. Successful treatment consisted of surgical debridement plus drainage, and tigecycline administration for three weeks.. Surgical source control along with effective antibiotics is essential in the treatment of mediastinitis. Tigecycline has the potential to be an option for pan-resistant A. baumannii mediastinitis.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cardiopulmonary Bypass; Debridement; Drainage; Drug Resistance, Multiple, Bacterial; Female; Humans; Mediastinitis; Middle Aged; Minocycline; Surgical Wound Infection; Tigecycline; Treatment Outcome

Multidrug-resistant Acinetobacter baumannii (MRAB) is an emerging cause of intensive care unit (ICU) outbreaks. Patients are the main reservoirs, inducing cross transmission. We describe an MRAB outbreak that occurred in the Prato Hospital ICU in June to August 2009.. The ICU consists of 2 separated 4-bed rooms (rooms A and B). The MRAB-positive patients were included in our study. During the outbreak, infection control measures were enhanced; patients and environmental screenings were performed. A 6-month follow-up was carried out.. Four of 26 patients admitted during the outbreak were MRAB positive. All patients were located in room A; no case was detected in room B either in the hospital or during the follow-up. Management included closure to new admissions, reinforcement of infection control measures, patient and environmental screenings, discharge of room B MRAB-negative patients for at least 5 days after the first case identification. All isolates were carbapenems resistant and tigecycline and colistin susceptible. All patients received tigecycline: 2 were successfully treated, 1 died because of preexisting illness, and 1 developed resistance and recovered after colistin therapy.. Enhanced infection control measures and adequate antibiotic strategy limited the outbreak. Tigecycline allowed rapid recovery. Nevertheless, resistance ensued; so colistin remained the only therapeutic option. However, pan-drug resistance has been reported.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Infective Agents; Colistin; Cross Infection; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Female; Humans; Infection Control; Intensive Care Units; Italy; Male; Middle Aged; Minocycline; Tigecycline; Treatment Outcome

The development of resistance is a compelling reason for reviewing administration of antibiotics. Recently, most Acinetobacter infections are caused by multidrug-resistant (MDR) strains which have necessitated the use of tigecycline or colistin. This study was undertaken to determine the susceptibility of Acinetobacter spp. to these and other drugs. A total of 250 Acinetobacter isolates were collected from the 8 government hospitals over a period of 6 months. Susceptibility to 18 antibiotics, including tigecycline and colistin, was investigated by determining their minimum inhibitory concentrations using E test. Of the 250 isolates, 13.6% and 12% were resistant to tigecycline and colistin. A total of 25.2% and 37.2% were resistant to imipenem and meropenem, respectively. Of the 250 isolates 88.4% were MDR. This relatively high prevalence of tigecycline and colistin-resistant isolates indicates an emerging therapeutic problem which may severely compromise the treatment of MDR Acinetobacter spp. infections in Kuwait.

Topics: Acinetobacter; Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Hospitals; Humans; Imipenem; Kuwait; Meropenem; Microbial Sensitivity Tests; Minocycline; Thienamycins; Tigecycline

Extensive drug resistance of Acinetobacter baumannii is a serious problem in the clinical setting. It is therefore important to find active antibiotic combinations that could be effective in the treatment of infections caused by this problematic 'superbug'. In this study, we analyzed the in vitro activities of three colistin-based combinations and a minocycline-based combination against clinically isolated extensive drug resistant Acinetobacter baumannii (XDR-AB) strains.. Fourteen XDR-AB clinical isolates were collected. The clonotypes were determined by polymerase chain reaction-based fingerprinting. Susceptibility testing was carried out according to the standards of the Clinical and Laboratory Standards Institute. Activities of drug combinations were investigated against four selected strains and analyzed by mean survival time over 12 hours (MST12 h) in a time-kill study.. The time-kill studies indicated that the minimum inhibitory concentration (MIC) of colistin (0.5 or 0.25 μg/mL) completely killed all strains at 2 to 4 hours, but 0.5×MIC colistin showed no bactericidal activity. Meropenem (8 μg/mL), minocycline (1 μg/mL) or rifampicin (0.06 μg/mL) did not show bactericidal activity. However, combinations of colistin at 0.5×MIC (0.25 or 0.125 μg/mL) with each of the above were synergistic and shown bactericidal activities against all test isolates. A combination of meropenem (16 μg/mL) with minocycline (0.5×MIC, 4 or 2 μg/mL) was synergitic to all test isolates, but neither showed bactericidal activity alone. The MST12 h values of drug combinations (either colistin- or minocycline-based combinations) were significantly shorter than those of the single drugs (p<0.01).. This study indicates that combinations of colistin/meropenem, colistin/rifampicin, colistin/minocycline and minocycline/meropenem are synergistic in vitro against XDR-AB strains.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; DNA Fingerprinting; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Intensive Care Units; Meropenem; Microbial Sensitivity Tests; Microbial Viability; Minocycline; Molecular Typing; Polymerase Chain Reaction; Rifampin; Thienamycins; Time Factors

Tigecycline was approved for the treatment of complicated intra-abdominal and complicated skin/skin structure infections. Because of its in vitro effectiveness for multidrug-resistant (MDR) isolates, tigecycline has been prescribed more broadly. This study evaluated tigecycline use after its first introduction in Taiwan and experience with tigecycline for the treatment of MDR Acinetobacter baumannii (MDRAB) infection, especially for ventilator-associated pneumonia.. Patients treated with tigecycline were collected retrospectively from February 2008 to July 2008 in Taipei Veterans General Hospital, a 2,900-bed tertiary care medical center in Taiwan. Patients were divided into three groups according to the indications: Group 1, Food and Drug Administration-approved indications; Group 2, health care-associated pneumonia (HAP); and Group 3, urinary tract infection, osteomyelitis, bacteremia, etc. Cases of MDRAB were also identified.. Among 66 cases, indications for the administration of tigecycline included Food and Drug Administration-approved indications (12, 18.2%), HAP (38, 57.6%), bacteremia (3, 4.5%), catheter-related infections (3, 4.5%), urinary tract infection (4, 6.1%), osteomyelitis (4, 6.1%), and others (2, 3%). Clinical outcome was positive in 20 cases, with higher clinical success rate for Group 1 than Group 2, which may correlate with higher Sequential Organ Failure Assessment score, older age, and more frequent intensive care admission in Group 2. Of the microbiologically evaluable cases, MDRAB predominated (33/51, 64.7%). Among infections with MDRAB (excluding pneumonia without ventilator), the clinical success rate was 12% (3/25).. The most common indication for the prescription of tigecycline was HAP. Success rate for MDRAB infection was lower than that previously reported, possibly because of serious underlying conditions and comorbidities in our patients. Because of limited choices, physicians should weigh the risk and benefit for prescribing tigecycline.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Aged, 80 and over; Anti-Bacterial Agents; Critical Illness; Humans; Middle Aged; Minocycline; Off-Label Use; Pneumonia, Ventilator-Associated; Retrospective Studies; Taiwan; Tigecycline; Treatment Outcome

The whole genomes of two Acinetobacter baumannii isolates recovered from a single patient were sequenced to gain insight into the nature and extent of genomic plasticity in this important nosocomial pathogen over the course of a short infection. The first, AB210, was recovered before tigecycline therapy and was susceptible to this agent; the second, AB211, was recovered after therapy and was resistant.. DNA from AB210 was sequenced by 454 GS FLX pyrosequencing according to the standard protocol for whole-genome shotgun sequencing, producing ∼250 bp fragment reads. AB211 was shotgun sequenced using the Illumina Genetic Analyzer to produce fragment reads of exactly 36 bp. Single nucleotide polymorphisms (SNPs) and large deletions detected in AB211 in relation to AB210 were confirmed by PCR and DNA sequencing.. Automated gene prediction detected 3850 putative coding sequences (CDSs). Sequence analysis demonstrated the presence of plasmids pAB0057 and pACICU2 in both isolates. Eighteen putative SNPs were detected between the pre- and post-therapy isolates, AB210 and AB211. Three contigs in AB210 were not covered by reads in AB211, representing three deletions of ∼15, 44 and 17 kb.. This study demonstrates that significant differences were detectable between two bacterial isolates recovered 1 week apart from the same patient, and reveals the potential of whole-genome sequencing as a tool for elucidating the processes responsible for changes in antibiotic susceptibility profiles.

Topics: Acinetobacter baumannii; Acinetobacter Infections; DNA, Bacterial; Drug Resistance, Bacterial; Genome, Bacterial; Humans; Minocycline; Molecular Sequence Data; Sequence Analysis, DNA; Tigecycline

Acinetobacter baumannii is a non-fermenting aerobic gram-negative bacteria and one of the important nosocomial pathogens, especially in intensive care units (ICUs). In recent years, multidrug-resistant (MDR) isolates have been an emerging problem, with limited therapeutic options. Tigecycline is a novel antimicrobial, with its in vitro activity against most gram-positive and gram-negative pathogens.. This is a retrospective study that was conducted in a tertiary care hospital with 550 beds in Ankara, Turkey, from January 2009 to July 2010. Thirty-three patients who had carbapenem-resistant Acinetobacter spp. infections and received tigecycline alone or in combination with other antibiotics for at least 3 days were included.. The median age of the patients was 62 (18-87) years. All of the patients were diagnosed and treated in the ICU. Clinical responses were observed in 23 patients (69.7%). Ten patients (30%) had clinical failure. There was no significant difference between ventilator-associated pneumonia (VAP) and bloodstream infection (BSI) in terms of clinical or microbiological outcome (p > 0.05). The microbiological response rate was 50%. Superinfection was detected in 13 patients (43.3%) and Pseudomonas aeruginosa was the most frequently isolated pathogen. The 30-day overall mortality rate and attributable mortality rates were 57.6 and 24.2%, respectively. The attributable mortality rate was higher in the group in which microbiological eradication was not provided.. Although it is approved by the Food and Drug Administration (FDA) for the treatment of complicated intra-abdominal infections, complicated skin and soft tissue infections, and community-acquired bacterial pneumonia, emerged resistance of Acinetobacter spp. and limited therapeutic options left physicians no choice but to use tigecycline for off-label indications.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenems; Drug Therapy, Combination; Drug Utilization; Female; Hospitals; Humans; Male; Middle Aged; Minocycline; Retrospective Studies; Tigecycline; Treatment Outcome; Turkey; Young Adult

To investigate the clinical implication and prognostic predictors of tigecycline treatment for pneumonia involving multidrug-resistant Acinetobacter baumannii (MDRAB).. A retrospective observational study over a 32-month period for adult patients receiving tigecycline treatment at least 7 days for pneumonia involving MDRAB.. We reviewed 112 patients with 116 episodes of tigecycline-treated pneumonia involving MDRAB. The mean age was 70.8 years. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 21.7. Seventy episodes (60.3%) had clinical resolution. The episodes with monomicrobial MDRAB pneumonia had a significantly lower clinical resolution rate than polymicrobial pneumonia (14/31, 45.2% vs. 56/85, 65.9%; p = 0.044). The independent predictors for failure of clinical resolution were female gender, malignancy, bilateral pneumonia, monomicrobial pneumonia, and higher APHCHE II scores. Forty-two episodes (36.2%) had the 30-day mortality, and the only independent predictor was deterioration of pneumonia on chest radiographs.. A high disease severity, bilateral pneumonia, and monomicrobial MDRAB pneumonia predicted failure of clinical resolution, and deterioration of pneumonia predicted mortality. MDRAB in monomicrobial pneumonia was the most certain to be causal. The clinical resolution rate from such pneumonia might reflect the ultimate efficacy of tigecycline in treating MDRAB pneumonia and the overall efficacy might be overestimated.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Aged, 80 and over; Anti-Bacterial Agents; APACHE; Bacteremia; Demography; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Minocycline; Pneumonia, Bacterial; Prognosis; Retrospective Studies; Severity of Illness Index; Sex Factors; Tigecycline; Treatment Outcome

The aim of this study was to evaluate the efficacy of tigecycline in multidrug-resistant (MDR) Acinetobacter baumannii pneumonia. We retrospectively evaluated the outcome of adult patients with culture proven MDR A. baumannii pneumonia treated with tigecycline between January 2009 and March 2011. The study comprised a total of 72 MDR A. baumannii pneumonia cases (44 men, mean age 65.9±15.0). Tigecycline was used for a mean duration of 10.7±4.8 days. Microbiological eradication was observed in 47 cases (65.3%). Overall mortality was 55.5% and was lower in cases with microbiological eradication vs others (15/47 32% vs 25/25 100%, p<0.0001). Mortality and microbiological eradication rates were not different with monotherapy vs combination therapy (p>0.05). Patients who died had lower albumin levels, higher APACHE-II scores and CRP levels. The microbiological eradication rate of tigecycline in MDR A. baumannii was considerable. However, eradication of A. baumannii did not result in favorable clinical outcomes in those patients with low albumin, higher APACHE-II scores and CRP levels.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Minocycline; Pneumonia, Bacterial; Retrospective Studies; Tigecycline

Acinetobacter baumannii is a Gram-negative coccobacillus causing serious nosocomial infections. The recent emergence of strains of bacteria, which are resistant to common antibiotics, has made the treatment of these infections increasingly complex. We report the case of a young patient affected by AIDS, who suffered brain toxoplasmosis and sepsis due to multidrug-resistant A baumannii. This bacterial infection was successfully treated with colistin and tigecycline. In addition, we review recent literature on this topic, from the year 2000 to date.

Topics: Acinetobacter baumannii; Acinetobacter Infections; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-HIV Agents; Child; Colistin; Diagnosis, Differential; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Electroencephalography; Enzyme-Linked Immunosorbent Assay; Humans; Magnetic Resonance Imaging; Male; Minocycline; Tigecycline; Tomography, X-Ray Computed

During an island-wide PCR-based surveillance study of beta-lactam resistance in multidrug-resistant (MDR) Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter calcoaceticus-baumannii complex isolates obtained from 17 different hospitals, 10 KPC-positive Acinetobacter isolates were identified. DNA sequencing of the bla(KPC) gene identified KPC-2, -3, and -4 and a novel variant, KPC-10. This is the first report of a KPC-type beta-lactamase identified in Acinetobacter species.

Topics: Acinetobacter; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; beta-Lactam Resistance; beta-Lactamases; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Population Surveillance; Puerto Rico

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Humans; Microbial Sensitivity Tests; Minocycline; Taiwan; Tigecycline

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Mutation; Tigecycline

The treatment of post-surgical meningitis due to multidrug-resistant (MDR) Acinetobacter baumannii is a therapeutic dilemma. The cases of two patients with MDR A. baumannii meningitis secondary to surgical site infections, successfully treated with combination regimens including tigecycline, are presented.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Humans; Male; Meningitis, Bacterial; Middle Aged; Minocycline; Neurosurgical Procedures; Surgical Wound Infection; Tigecycline

Topics: Acinetobacter; Acinetobacter Infections; Anti-Bacterial Agents; Cross Infection; Disk Diffusion Antimicrobial Tests; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Minocycline; Tigecycline

To describe cerebral spinal fluid (CSF) penetration of tigecycline.. A 38-year-old woman experienced a right internal carotid artery dissection and right anterior and middle cerebral artery strokes due to unknown causes and subsequently developed vasogenic edema requiring right hemi-craniectomy. Her postoperative course was complicated by multiple infections, and she developed multidrug, carbapenem-resistant Acinetobacter baumannii cerebritis. She was treated with a prolonged course of multiple antibiotics, including 18 days of therapy with tigecycline. Time-paired serum and CSF samples were obtained, and tigecycline concentrations were analyzed by high-performance liquid chromatography. We report serial, steady-state, serum, and CSF concentrations of tigecycline when administered in the Food and Drug Administration-approved dose of 50 mg every 12 hours. CSF concentrations remained relatively stable, suggesting that tigecycline did not accumulate in the CSF, at least in our patient. Tigecycline concentrations in the CSF were between 0.035 and 0.048 mg/L, while corresponding serum concentrations were 0.097-0.566 mg/L. The calculated tigecycline penetration ratio in this patient ranged from 0% to 52%, depending on the calculation methodology utilized.. Concentrations, regardless of sample timing relative to dose, remained relatively stable in the CSF of our patient. The pharmacodynamic profile of tigecycline is not completely elucidated; however, it is presumed that the drug must be at the site of infection for efficacy. Our patient never obtained tigecycline concentrations in excess of the minimum inhibitory concentration for A. baumannii in either the serum or the CSF.. Our patient experienced low CSF tigecycline concentrations and failed to achieve a clinical response while on therapy. CSF drug disposition of tigecycline requires further systematic study to fully elucidate the pharmacokinetic profile. Reduced CSF concentrations urge caution in the treatment of cerebritis with standard dosing of tigecycline.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Chromatography, High Pressure Liquid; Encephalitis; Female; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline; Treatment Outcome

The in vivo activity of tigecycline was evaluated in an experimental pneumonia model (C57BL/6 mice) by Acinetobacter baumannii. Two clinical strains were used: minimum inhibitory concentrations (MICs) of imipenem and tigecycline 1 and 2 microg/mL (imipenem-susceptible, IPM-S), and 8 and 2 microg/mL (imipenem-intermediate, IPM-I), respectively. For imipenem (30 mg/Kg), T/CMI (h) were 1.04 and 0.51 for IPM-S and IPM-I, respectively. For tigecycline (5 mg/Kg), the area under the concentration-time curve (AUC)/MIC(0-24 h) (serum and lung) were 9.24 and 4.37 (for the two strains), respectively. In the efficacy experiments with the IPM-S, imipenem (log CFU/g 3.59 +/- 0.78, p = 0.006) and tigecycline (2.82 +/- 1.2, p = 0.054) decreased the bacterial counts in lungs with respect to its controls; with the IPM-I, both imipenem (1.21 +/- 0.52, p = 0.002) and tigecycline (3.21 +/- 0.28, p = 0.035) decreased the bacterial counts with respect to the controls. In the survival experiments, with the IPM-S, the mortality was the same in the control (67%) and in the tigecycline (77%) groups, and imipenem reduced it (21%, p = 0.025); with the IPM-I, the mortality was the same in the control (87%) and in the tigecycline (85%) groups, and imipenem (0%) reduced it (p < 0.001). In summary, the present study shows that tigecycline is less efficacious than imipenem in the treatment of experimental A. baumannii pneumonia caused by IPM-S and IPM-I strains.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Area Under Curve; Disease Models, Animal; Female; Imipenem; Lung; Mice; Mice, Inbred C57BL; Minocycline; Pneumonia, Bacterial; Statistics, Nonparametric; Tigecycline

Topics: Acinetobacter Infections; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae Infections; Humans; Minocycline; Tigecycline; Urinary Tract Infections

Tigecycline is a promising therapeutic option against many current multidrug resistant pathogens. The aim of this retrospective study was to determine the clinical and microbiological outcomes of patients treated with tigecycline for serious infections caused by carbapenem-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii complex (Acb-complex). A retrospective study was conducted to define the patients who received tigecycline for carbapenem-resistant Acb-complex infections between 1 June, 2008 and 1 may, 2009. A total of 21 patients were eligible for the study. The median age of the patients was 48 years and 6 patients were female. Eighteen patients were treated with tigecycline for carbapenemresistant Acb-complex as the sole microorganism while 3 received it for polymicrobial infections. All Acb-complex isolates were susceptible to tigecycline. The most common indication of tigecycline treatment was surgical-site infections (SSI) followed by ventilator associated pneumonia (VAP). Tigecycline was the sole antibiotic administered in 7 patients while concurrent antibiotics were used in 14 patients. The median duration of tigecycline therapy was 14 days. Two patients died within 14 days of initiating treatment, representing an attributable mortality rate of 9.5% while 4 patients died within 30 days representing a crude mortality rate of 19.1%. Seventeen out of 21 patients had successful clinical outcomes, cure in 11 patients and improvement in 6. Fourteen of 21 patients had microbiological failure. Correlation between microbiological response with clinical outcome was poor. Clinical failure was more common in patients with VAP. Patients with bacteremia were more likely to have microbiological failure while microbiological outcome was better in patients with SSI. In this retrospective study, 81% (17 of 21) of the patients infected with carbapenem-resistant Acb-complex had a positive outcome under tigecycline therapy. However, these preliminary results should be evaluated cautiously in the absence of well-controlled studies.

Topics: Acinetobacter baumannii; Acinetobacter calcoaceticus; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Carbapenems; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Minocycline; Retrospective Studies; Tigecycline; Young Adult

The relationship between expression of adeABC and minimal inhibitory concentration (MIC) of tigecycline was investigated by RT-PCR and statistical analyses in a population of 106 clinical isolates (MIC range, 0.0313-16 microg/ml) of Acinetobacter calcoaceticus-Acinetobacter baumannii complex. There was a statistically significant linear relationship (p < 0.0001) between log-transformed expression values and log-transformed MIC values, indicating that overexpression of AdeABC efflux pump is a prevalent mechanism for decreased susceptibility to tigecycline in A. calcoaceticus-A. baumannii complex.

Topics: Acinetobacter baumannii; Acinetobacter calcoaceticus; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; Drug Resistance, Bacterial; Humans; Membrane Transport Proteins; Microbial Sensitivity Tests; Minocycline; Reverse Transcriptase Polymerase Chain Reaction; Tigecycline

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Cross Infection; Drug Resistance, Bacterial; Drug Synergism; Humans; Intensive Care Units; Meropenem; Microbial Sensitivity Tests; Minocycline; Sulbactam; Thienamycins; Tigecycline

The Aga Khan University Hospital is a tertiary care centre in Karachi, Pakistan, where tigecycline has not been used previously. We report findings of a pre-use in vitro study to evaluate sensitivity of nosocomial Acinetobacter spp. Tigecycline minimum inhibitory concentration (MIC) was correlated with that of other tetracyclines to assess their predictive potential.. Acinetobacter spp. were collected from hospitalized inpatients admitted to Aga Khan University Hospital from April to November 2007. Tigecycline, tetracycline, doxycycline, and minocycline MICs were determined by E-test.. One hundred isolates of Acinetobacter spp. were tested. Ninety-eight percent of Acinetobacter spp. were carbapenem-resistant. Tigecycline MIC(50) and MIC(90) were 1.5 and 2.0 microg/ml, respectively. Unavailability of standard breakpoints hindered categorization of these values. Minocycline was highly active, with MIC(90) of 2.0 microg/ml.. Tigecycline breakpoints for Acinetobacter spp. should be established to prevent injudicious use of this antibiotic based on misleading in vitro results. The therapeutic potential of minocycline needs more in-depth study.

Topics: Acinetobacter; Acinetobacter Infections; Carbapenems; Drug Resistance, Multiple, Bacterial; Hospitals, University; Humans; Microbial Sensitivity Tests; Minocycline; Pakistan; Tetracyclines; Tigecycline

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Cross Infection; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

The tigecycline may represent a therapeutic alternative for the control of multiresistant A. baumannii, although there is no consensus regarding the cutoff points for sensitivity or variability of MIC as a function of culture medium used for the antibiogram against this microorganism. Therefore, our objective was to verify this variability, and propose the culture medium that comes closest to the standard method.. We selected 41 strains of carbapenem-resistant A. baumannii. We analyzed the sensitivity to tigecycline in different culture media: Mueller Hinton agar Oxoid commercial (C-MH), Mueller Hinton fresh agar BD and Co., USA (F-MH) and ISO-sensitest fresh agar Oxoid, using the E-test and disk. The MICs were compared against those obtained using the technique standard of macrodilution.. The mean MIC and inhibition diameters obtained in the different culture media corresponded to 9.26 mg/L and 15.1 mm in diameter for MH-C, 1.71 mg/L and 22.7 mm for MH-F; 2.68 mg/L and 20.8 mm for ISO-sensitest. Half the MIC obtained by the standard method of dilution was 0.47 mg/L (SD =0.21), with values between 0.25 and 1 mg/L.. In the three growth media studied, MICs superior to the standard are observed, which is false to interpret resistance in many cases. However, the medium that comes closer more that of reference is the MH-F.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Culture Media; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Reproducibility of Results; Tigecycline

Acinetobacter baumannii are emerging as the causal agents of healthcare-associated infections. We describe arenal transplant recipient who developed bacteremia caused by multiresistant A. baumannii, which received a combination of tigecycline, colistin, and meropenem in continuous infusion. The clinical outcome was favorable. In this article we made a molecular study of this multiresistant strain. Our analysis reveals the presence of abla-OXA-72 gene,a class D of oxacillinase belonging to bla-OXA-40-like group,which constitutes the most disseminated familiy of carbapenemases in Spain. Thus, we found different susceptibility patterns of A. baumannii when we used different Mueller-Hinton agars with different manganese concentrations. Lastly, we explain the combination of these three antibiotics administered to increase microbiologic and pharmacodynamic yield.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Colistin; Drug Combinations; Drug Resistance, Multiple, Bacterial; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Meropenem; Microbial Sensitivity Tests; Minocycline; Reverse Transcriptase Polymerase Chain Reaction; Thienamycins; Tigecycline

Lung transplantation (LTX) requires continual systemic immunosuppression, which can result in infections that may compromise recipient survival. A recent outbreak of Acinetobacter baumannii at our institution resulted in infections experienced in both LTX recipients and nontransplant patients. A retrospective review was conducted of patients who had A. baumannii recovered from blood, other normally sterile body fluids, and/or respiratory secretions and who had clinical follow-up extending to 1 year postinfection. A. baumannii was considered "multidrug-resistant" when its growth was not inhibited by minimum inhibitory concentrations of multiple antibiotics. Despite the resistance profile, patients were treated with a combination of antibiotics, which included tigecycline, colistimethate, and when susceptible, imipenem. Once infection was diagnosed, immunosuppression was reduced in all LTX recipients. Six LTX recipients became infected with A. baumannii and were contrasted to infections identified in 14 non-LTX, nonimmunosuppressed patients. A. baumannii was persistently recovered in 4 of 6 LTX recipients (66.7%) compared with only 1 of 14 (7.1%) non-LTX patients (χ(2) = 9.9, p = 0.005). LTX recipients received antibiotic therapy for an average of 76 ± 18.4 days compared with 16.0 ± 6.8 days for the non-LTX patients (p = 0.025, Mann-Whitney U test). All 4 of the 6 (66.7%) LTX recipients died as a consequence of their infection compared with 1 of 14 (7.1%) of the non-LTX patients (χ(2) = 9.9, p = 0.005). Despite receiving more antibiotic therapy, LTX recipients who were infected with multidrug-resistant A. baumannii were less likely to clear their infection and experienced greater mortality compared with non-LTX patients.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Humans; Imipenem; Immunosuppressive Agents; Lung Transplantation; Minocycline; Pneumonia, Bacterial; Radiography; Retrospective Studies; Tigecycline

Our aim was to determine the prevalence of multidrug resistance of Acinetobacter baumannii and other pathogens at a tertiary-care teaching hospital in Mexico over a 3-year period. Clinical isolates of A. baumannii (n = 550), Pseudomonas aeruginosa (n = 250), some Enterobacteriaceae species (n = 500) and Staphylococcus aureus (n = 250) collected over a 3-year period were included. Susceptibility tests were performed by the broth microdilution method. 74% of A. baumannii, 40% of Escherichia coli, 34% of P. aeruginosa, 22% of Klebsiella pneumoniae, 9% of Enterobacter cloacae, and 7% of Serratia sp. were multidrug resistant. 59% of A. baumannii clinical isolates were meropenem-resistant. A. baumannii isolates from the lower respiratory tract were the most susceptible, followed by urine clinical isolates. Species from Enterobacteriaceae showed susceptibility rates higher than 90% to meropenem and tigecycline and Serratia sp. showed the highest susceptibility to the drugs evaluated. For P. aeruginosa, the most potent drug was levofloxacin, followed by meropenem and piperacillin-tazobactam. With regard to S. aureus, 96% of the isolates were susceptible to vancomycin, followed by tigecycline and minocycline (91% of strains susceptible). The high multidrug resistance observed underscores the need for surveillance of bacterial drug resistance.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Hospitals, Teaching; Humans; Klebsiella pneumoniae; Meropenem; Mexico; Microbial Sensitivity Tests; Minocycline; Prevalence; Pseudomonas aeruginosa; Pseudomonas Infections; Staphylococcus aureus; Thienamycins; Tigecycline

Thirteen clinical isolates of multidrug-resistant Acinetobacter baumannii resistant to carbapenems (MRAB-C) with tigecycline nonsusceptibility were collected from individual patients in this study. None of the 13 isolates shared the same strain characteristics in molecular typing. All of them showed increased adeB transcription, as predicted. However, none of these tigecycline-nonsusceptible MRAB-C isolates were found to possess previously known adeRS mutations. Upregulation of adeB transcription may result from cross stimulation by other mechanisms.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Aged, 80 and over; Bacterial Proteins; Carbapenems; Drug Resistance, Bacterial; Female; Humans; Male; Membrane Transport Proteins; Middle Aged; Minocycline; Molecular Sequence Data; Mutagenesis, Insertional; Reverse Transcriptase Polymerase Chain Reaction; Tigecycline

A total of 5127 Acinetobacter spp. were collected from 140 hospitals in 32 countries in North America (17.1%), Europe (22.9%), Latin America (25.2%), and the Asia-Pacific (APAC) region (34.8%). Tigecycline MIC distributions were bimodal against isolates from North America and APAC region, while a unimodal pattern was noted for strains from Latin America. A variable MIC distribution was noted in Europe. Only tigecycline (MIC(50/90), 0.5/2 μg/mL) and polymyxin B (MIC(50/90), 0.5/1 μg/mL; 98.6% susceptible) exhibited high activity against Acinetobacter spp. Overall, tigecycline inhibited at least 90.0% of Acinetobacter spp. isolates from all countries evaluated at ≤2 μg/mL, as well as 95.0% of those displaying multidrug resistance. Other tested agents showed limited activity and a significant (P < 0.001) trend toward decreased susceptibility during the study period.

Topics: Acinetobacter; Acinetobacter Infections; Anti-Bacterial Agents; Asia; Cross Infection; Europe; Hospitals; Humans; Latin America; Microbial Sensitivity Tests; Minocycline; North America; Polymyxin B; Tigecycline

Acinetobacter baumannii is a frequent cause of nosocomial infections in most hospitals. Management of infections caused by these strains is difficult, as the strains often display multiple drug resistance, including carbapenem. Tigecycline which is a glycylcycline derivative has antimicrobial activity against many gram-positive and gram-negative organisms. In this study, in vitro activity of tigecycline and carbapenems against clinical isolates of A.baumannii strains were investigated. A total of 100 A.baumannii isolates were collected from hospitalized patients with documented nosocomial infections [pneumonia (n = 39), surgical wound infection (n = 32), bacteremia (n = 16), catheter infection (n = 6), urinary tract infection (n = 5), peritonitis (n = 1), eye infection (n = 1)] between October 2006 and June 2007. Only one isolate per patient was included to the study. Minimum inhibitory concentrations (MIC) of tigecycline were determined by E-test (AB Biodisk, Sweden). Carbapenem resistance of A.baumannii strains were determined by disk diffusion method. All of the 100 A.baumannii isolates (100%) were found susceptible to tigecycline (MIC values ≤ 2 µg/ml; MIC ranges: 0.032-1.5 µg/ml). Imipenem susceptibility test was performed for 95 strains, and 36 (37.9%) were found sensitive, 18 (18.9%) were intermediate sensitive, and 41 (43.2%) were resistant. Meropenem susceptibility test was performed for 87 strains, and 22 (25.3%) were found sensitive, 9 (10.3%) were intermediate sensitive, and 56 (64.4%) were resistant. Since tigecycline is found quite effective on nosocomial A.baumannii isolates, it may be considered as a treatment alternative in infections caused by carbapenem-resistant Acinetobacter spp.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Cross Infection; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

Colistin sulfate and levofloxacin, alone and in combination with tigecycline, were investigated for their in vitro activities and postantibiotic effects (PAEs) on6 meropenem-resistant Acinetobacter baumannii.. The in vitro activities of colistin sulfate and levofloxacin in combination with tigecycline were determined using a microbroth checkerboard technique. The results were interpreted based on the fractional inhibitory concentration index. To determine the PAEs, A. baumannii strains in the logarithmic phase of growth were exposed for 1 h to antibiotics, alone and in combination. Recovery periods of test cultures were evaluated using viable counting after centrifugation.. One synergistic interaction was observed for each of the tigecycline-colistin sulfate and tigecycline-levofloxacin combinations. Colistin sulfate produced a strong PAE ranging from 2.50 to 7.0 h in a concentration-dependent manner. PAEs were induced by levofloxacin (ranging from 0.35 to 2.45 h) and tigecycline (ranging from 0.05 to 1.40 h). In combination, tigecycline slightly changed the PAE of colistin sulfate and levofloxacin against the studied strains.. This study's findings could have important implications for the timing of doses during antimicrobial therapy with tigecycline, colistin sulfate, and levofloxacin alone and in combination.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Humans; Levofloxacin; Meropenem; Microbial Sensitivity Tests; Minocycline; Ofloxacin; Thienamycins; Tigecycline

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

Topics: Acinetobacter; Acinetobacter Infections; Anti-Bacterial Agents; Drug Resistance, Bacterial; Humans; Korea; Microbial Sensitivity Tests; Minocycline; Tigecycline

Multidrug-resistant Acinetobacter baumannii (MRAB) is an increasing problem in UK hospitals, with many strains now resistant to all available antibiotics except polymyxins. Tigecycline has been used for the treatment of MRAB as it demonstrates activity in vitro, but there are limited data on its clinical efficacy in Gram-negative infections, especially those involving the lower respiratory tract or bacteraemia.. A retrospective study of the clinical and microbiological outcomes of all patients treated with tigecycline for MRAB over an 18 month period was undertaken.. Thirty-four patients received tigecycline for MRAB or polymicrobial infection involving MRAB. Twenty-three (68%) had a positive clinical outcome: microbiological clearance was demonstrated in 10 of these. The overall mortality was 41% (n = 14), with nine deaths directly attributable to sepsis. Three patients had episodes of Gram-negative bacteraemia while receiving treatment with tigecycline, with documented resistance occurring in one patient. Overall, the correlation between microbiological and clinical outcomes was poor.. While tigecycline retains excellent in vitro activity against MRAB, its clinical efficacy remains uncertain. A prospective study, including the use of tigecycline in combination with other antimicrobial agents, should be undertaken to define its role in the treatment of MRAB.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Anti-Bacterial Agents; Child; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Minocycline; Retrospective Studies; Tigecycline; Treatment Outcome; United Kingdom; Young Adult

Tigecycline is an extended-spectrum antibiotic with activity against Acinetobacter spp. (ACB), an increasingly common cause of nosocomial pneumonia. Although this compound is under investigation for this indication, supportive pharmacodynamic data are not yet available at this infection site. The objective of this study was to characterize the exposure-response relationship of tigecycline with ACB in an established murine pneumonia model.. The pharmacokinetic profile of tigecycline was evaluated in infected neutropenic mice. Tigecycline 6.25, 12.5, 25, 50, 100, 200, 300 and 400 mg/kg, in single or two to six divided subcutaneous doses, were tested against all ACB isolates. Efficacy, defined as the log(10) change in bacterial cfu/mL, was assessed after a 24 h course of therapy. Tigecycline exposures in serum were corrected for dose-specific protein binding. The relationship between the area under the free concentration-time curve to MIC (fAUC/MIC) and change in bacterial density was determined using the sigmoid E(max) model.. Tigecycline displayed linear pharmacokinetics with a mean half-life of 11.3 +/- 1.4 h. Efficacy correlated well with fAUC/MIC (R(2) = 0.96). The mean 80%, 50% effective and stasis exposures (fAUC/MIC) were 17, 8 and 6, respectively. Maximal efficacy for the five Acinetobacter baumannii studied was 3.4 log kill.. Tigecycline efficacy in this murine ACB pneumonia model was well predicted by fAUC/MIC. Requisite tigecycline exposures for efficacy appear to be higher for ACB pneumonia than for other pathogens reported of non-respiratory infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Colony Count, Microbial; Female; Half-Life; Mice; Microbial Sensitivity Tests; Minocycline; Pneumonia, Bacterial; Serum; Tigecycline

This observational retrospective study aims to present early experience with tigecycline (TIG) in the treatment of infections due to multi-drug resistant (MDR) microorganisms.. Adult patients included, received TIG for >5 days either as monotherapy (M group) or as presumed active monotherapy (PAM group). In the PAM group, all co-administered antimicrobial(s) were resistant in vitro against the targeted pathogen(s) or had been clinically and microbiologically failing after >or=5 days of therapy despite in vitro susceptibility.. Forty-five patients (35 in ICU) were treated for 28 Acinetobacter baumannii and 23 Klebsiella pneumoniae infections [21 ventilator-associated and healthcare-acquired pneumonia (VAP/HCAP), 10 bloodstream infections (BSI) and 14 surgical infections (SI)]. Successful overall clinical outcome was 80%, i.e. 81.8% in M group, 78.3% in PAM group, 90.5% in VAP/HCAP, 80% in BSI, 64.3% in SI and 85% in the cases with septic shock. Superinfections from Enterobacteriaceae inherently resistant to tigecycline occurred in 31.8% of M and 13% of PAM group (p<0.001).. TIG represents a promising option in infections from MDR pathogens, however, further clinical experience is required.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Analysis of Variance; Anti-Bacterial Agents; Bacteremia; Chi-Square Distribution; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Logistic Models; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Ventilator-Associated; Retrospective Studies; Shock, Septic; Surgical Wound Infection; Tigecycline

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Minocycline; Sepsis; Serum; Tigecycline; Urinary Tract Infections; Urine

Infections sustained by multidrug-resistant (MDR) and pan-resistant Acinetobacter baumannii have become a challenging problem in Intensive Care Units. Tigecycline provided new hope for the treatment of MDR A. baumannii infections, but isolates showing reduced susceptibility have emerged in many countries, further limiting the therapeutic options. Empirical combination therapy has become a common practice to treat patients infected with MDR A. baumannii, in spite of the limited microbiological and clinical evidence supporting its efficacy. Here, the in vitro interaction of tigecycline with seven commonly used anti-Acinetobacter drugs has been assessed.. Twenty-two MDR A. baumannii isolates from Intensive Care Unit (ICU) patients and two reference strains for the European clonal lineages I and II (including 3, 15 and 6 isolates that were resistant, intermediate and susceptible to tigecycline, respectively) were tested. Antimicrobial agents were: tigecycline, levofloxacin, piperacillin-tazobactam, amikacin, imipenem, rifampicin, ampicillin-sulbactam, and colistin. MICs were determined by the broth microdilution method. Antibiotic interactions were determined by chequerboard and time-kill assays. Only antibiotic combinations showing synergism or antagonism in both chequerboard and time-kill assays were accepted as authentic synergistic or antagonistic interactions, respectively.. Considering all antimicrobials in combination with tigecycline, chequerboard analysis showed 5.9% synergy, 85.7% indifference, and 8.3% antagonism. Tigecycline showed synergism with levofloxacin (4 strains; 16.6%), amikacin (2 strains; 8.3%), imipenem (2 strains; 8.3%) and colistin (2 strains; 8.3%). Antagonism was observed for the tigecycline/piperacillin-tazobactam combination (8 strains; 33.3%). Synergism was detected only among tigecycline non-susceptible strains. Time-kill assays confirmed the synergistic interaction between tigecycline and levofloxacin, amikacin, imipenem and colistin for 5 of 7 selected isolates. No antagonism was confirmed by time-kill assays.. This study demonstrates the in vitro synergistic activity of tigecycline in combination with colistin, levofloxacin, amikacin and imipenem against five tigecycline non-susceptible A. baumannii strains, opening the way to a more rationale clinical assessment of novel combination therapies to combat infections caused by MDR and pan-resistant A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Typing Techniques; DNA Fingerprinting; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Drug Synergism; Genotype; Humans; Intensive Care Units; Microbial Sensitivity Tests; Microbial Viability; Minocycline; Mutation; Random Amplified Polymorphic DNA Technique; Rome; Tigecycline

The incidence of Acinetobacter baumannii infection has greatly increased over recent decades with infections occurring more in critically ill hospitalised patients. Hospital outbreaks of multiple antibiotic-resistant strains are posing an increasing threat to public health. Three different outbreaks of multidrug-resistant A. baumannii (MRAB) infections involving 24 patients, aged 16-75 years occurred in the intensive care unit in the course of one year. The isolates were cultured from clinical samples and identified using automated Vitek II ID system and the API 20NE system. Susceptibility testing was done by the E-test method. Molecular typing of the isolates was determined by pulsed-field electrophoresis. Screening of both patients and the environment was carried out. The acquisition time, i.e. the time of admission to time of acquiring infection, ranged from 3 to 31 days. All isolates were multiply resistant (MRAB), including resistance to carbapenems (MRAB-C) in the majority of cases but susceptible to tigecycline, with a minimum inhibitory concentration (MIC(90)) of 2 microg/mL. The overall mortality rate was 16.7%. Time-to-clearance of the MRAB-C was 8.3 days in the first outbreak, when tigecycline was not used, and 2.8 and 3.1 days during the second and third outbreaks, respectively, when tigecycline was used, and all but one patient survived. Environmental screening revealed gross contamination of many surfaces and equipment within the unit. The outbreak strains belonged to two distinct clones (D and E) whereas the 14 environmental strains belonged to three distinct groups (A-C). The outbreak of infections treated with tigecycline was successfully eliminated in conjunction with an aggressive infection control strategy.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacterial Typing Techniques; Carbapenems; Cross Infection; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Environmental Microbiology; Humans; Incidence; Intensive Care Units; Microbial Sensitivity Tests; Middle Aged; Minocycline; Molecular Epidemiology; Tigecycline; Young Adult

Tigecycline seems to be a promising agent for treatment of resistant Acinetobacter baumannii infections, however approved criteria for susceptibility testing are still lacking. The aim of this study was to evaluate tigecycline activity against multidrug resistant A. baumannii clinical isolates, as well as susceptibility testing methods and disk diffusion (DD) breakpoints. Reference broth microdilution (BMD), Etest and DD methods were used. MIC(50 )and MIC(90 )by the reference method were 1 and 8 microg/ml, respectively. Applying the breakpoints for enterobactericeae, 85.7% of the isolates were sensitive to tigecycline. The Etest resulted in lower susceptibility rates (63.7%). Essential agreement between Etest and BMD was 75.8%. 21.9% of the strains were susceptible by BMD and intermediate by Etest. Provisional DD breakpoints >or=19/or=17/or=17/

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Diagnostic Errors; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Quality Control; Tigecycline

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carrier State; Critical Illness; Disease Outbreaks; Drug Resistance, Bacterial; Humans; Incidence; Microbial Sensitivity Tests; Minocycline; Tigecycline

This survey was conducted to evaluate the in vitro activity of tigecycline against 50 isolates of multidrug-resistant (MDR) Acinetobacter baumannii. Isolates of A. baumannii were resistant to ciprofloxacin, chloramphenicol, imipenem, levofloxacin, piperacillin and piperacillin-tazobactam, but were always susceptible to colistin. MICs of tigecycline were determined by E-test in Mueller-Hinton agar. The results of the study showed that 50% of the A. baumannii strains were susceptible to tigecycline.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Drug Resistance, Multiple; Humans; Intensive Care Units; Microbial Sensitivity Tests; Minocycline; Tigecycline

Acinetobacter baumannii is an important pathogen, capable of survival for very long periods on various surfaces in the hospital environment. Tigecycline is a commonly used antimicrobial agent especially for the treatment of resistant infections. The aim of this study was to investigate the activity of tigecycline on both planktonic and sessile biofilm cells of A. baumannii strains isolated from blood cultures and to compare the efficiency in terms of biofilm synthesis. Tigecycline activity on 59 A. baumannii strains was examined by agar dilution technique. The ability of strains to form biofilm was evaluated by adherence on polystyrene surfaces in brain heart infusion broth supplemented with 0.25% glucose. Time-kill technique was used for determination of the time and concentration dependent activity of tigecycline on biofilm positive and negative strains. The planktonic cells in logarithmic growth phase were exposed to tigecycline at 0.5, 1, 2, 4, ve 8 x minimum inhibitory concentration (MIC) concentrations and colony counts were evaluated after 0, 2, 4, 6, 24 and 48 hours. The effect of tigecycline on sessile cells was studied on biofilm matrix composed around plastic beads. Tigecycline susceptibility rate of planktonic cells was 89.8% and MIC50 and MIC90 values were 1 and 2 microg/ml, respectively. Biofilm formation was detected in 52.5% of isolates and no significant correlation was found between MIC values and biofilm production of the strains (p > 0.05). Tigecycline showed a potent antibacterial activity against planktonic cells regardless of biofilm forming capability of strains. Biofilm inhibitory concentrations of sessile cells were elevated significantly. As a result, tigecycline showed a potent activity on planktonic A. baumannii cells however, the effect was decreased significantly on sessile cells in biofilm environment. The results suggest that, the possibility of decreased sensitivity of cells in biofilm environment should be considered as well as antibiotic sensitivity test results during the treatment of infections caused by A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Adhesion; Biofilms; Colony Count, Microbial; Humans; Microbial Sensitivity Tests; Minocycline; Plankton; Tigecycline

Forty-two multidrug-resistant (MDR) Acinetobacter baumannii isolates were obtained during outbreaks in a Korean hospital. The co-carriage of bla(OXA-23), bla(OXA-51), bla(PER-1) and armA was observed in 23 isolates, and they were susceptible only to colistin and minocycline. The MDR A. baumannii isolates were found to belong to sequence group 1 using sequence-based typing.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Bacterial Typing Techniques; beta-Lactamase Inhibitors; beta-Lactamases; Carbapenems; Colistin; Cross Infection; Disease Outbreaks; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Humans; Korea; Microbial Sensitivity Tests; Minocycline; Polymerase Chain Reaction; Sequence Analysis, DNA

We present 6 cases of multidrug-resistant (MDR) Acinetobacter baumannii pneumonia in lung transplant recipients. All cases were treated with imipenem and/or non-traditional antibiotics, such as tigecycline and colistimethate, and had different microbiologic and clinical outcomes. Prior treatment with broad-spectrum anti-microbial therapy was the single most likely risk factor for the development of infection due to MDR Acinetobacter baumannii. Ideal preventive and therapeutic strategies for this pathogen in lung transplant recipients require further study.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Infective Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Imipenem; Lung Transplantation; Male; Minocycline; Pneumonia; Risk Factors; Tigecycline; Treatment Outcome

Acinetobacter infections resistant to multiple classes of antibiotics have become prevalent in many institutions. Tigecycline has in vitro activity against Acinetobacter spp. and has been suggested as a therapeutic option in these infections.. To describe the clinical and microbiologic outcomes of patients who received tigecycline for the treatment of infections caused by Acinetobacter spp. at our institution.. A retrospective review was conducted of the medical records of 29 sequential patients who received tigecycline for treatment of Acinetobacter infections. The outcomes assessed for efficacy were clinical improvement or cure and microbiologic cure in evaluable patients.. Patients received tigecycline a median of 30 days into hospitalization for a median of 11 days. Common indications were pneumonia (15 pts.), bacteremia (6), and urinary tract infection (3). Positive clinical outcomes (clinical cure or improvement) were seen in 8 (28%) of 29 patients. Of the 25 microbiologically evaluable patients, 11 (44%) had resolution of their cultures. Eleven patients had susceptibility testing performed, and the median minimum inhibitory concentration was 4 microg/mL (range 3-8).. In this case series, most patients did not have clinically or microbiologically favorable outcomes with tigecycline therapy. No patient had an isolate that was fully susceptible to tigecycline. Data from more studies are needed before tigecycline can be recommended for the treatment of Acinetobacter infections.

Topics: Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Bronchitis; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Bacterial; Retrospective Studies; Tigecycline; Urinary Tract Infections; Wound Infection

Topics: Acinetobacter; Acinetobacter Infections; Anti-Bacterial Agents; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

Tigecycline is the first of a new class of antibiotics named glycylcyclines and it was approved for the treatment of complicated intra-abdominal infections and complicated skin and skin structure infections. Notwithstanding this, tigecycline's pharmacological and microbiological profile which includes multidrug-resistant pathogens encourages physicians' use of the drug in other infections. We analyzed, during the first months after its launch, the tigecycline prescriptions for 113 patients in 12 institutions. Twenty-five patients (22%) received tigecycline for approved indications, and 88 (78%) for "off label" indications (56% with scientific support and 22% with limited or without any scientific support). The most frequent "off label" use was ventilator associated pneumonia (VAP) (63 patients). The etiology of infections was established in 105 patients (93%). MDR-Acinetobacter spp. was the microorganism most frequently isolated (50% of the cases). Overall, attending physicians reported clinical success in 86 of the 113 patients (76%). Our study shows that the "off label" use of tigecycline is frequent, especially in VAP. due to MDR-Acinetobacter spp., where the therapeutic options are limited (eg: colistin). Physicians must evaluate the benefits/risks of using this antibiotic for indications that lack rigorous scientific support.

Topics: Abdominal Cavity; Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Drug Labeling; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae Infections; Female; Humans; Male; Middle Aged; Minocycline; Prospective Studies; Skin Diseases, Bacterial; Soft Tissue Infections; Staphylococcal Infections; Tigecycline; Treatment Outcome; Young Adult

We performed susceptibility testing using the microdilution method to determine the in-vitro activity of tigecycline against 393 Acinetobacter baumannii clinical isolates collected in 2006 from 19 hospitals in Taiwan. Significant proportions of the isolates were resistant to imipenem (44%), ciprofloxacin (75%), amikacin (69%), sulbactam (34%) and all four antibiotics (22%), and susceptibility to tigecycline among these different resistant phenotypes of A. baumannii varied from 71% to 82%. The minimum inhibitory concentration (MIC) of tigecycline ranged from 0.6 to 16 microg/mL (MIC(50) 2 microg/mL; MIC(90) 4 microg/mL). The cumulative curve of tigecycline MICs showed that when the MIC cut-offs were set at 2 microg/mL and 4 microg/mL, 80.9% and 93.1% of the isolates were susceptible, respectively. As tigecycline will be used in the future for infections caused by multidrug-resistant A. baumannii because of limited antibiotic choice, and as resistance to tigecycline in A. baumannii isolates may develop following antibiotic exposure, continuous monitoring of the susceptibility of A. baumannii isolates to tigecycline is warranted.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Humans; Microbial Sensitivity Tests; Minocycline; Taiwan; Tigecycline

A total of 393 isolates of A. baumannii were collected from patients treated at 19 teaching hospitals in Taiwan. Minimum inhibitory concentrations (MICs) and inhibitory zone diameters for tigecycline were determined by the broth microdilution method and the disk diffusion method, respectively. The MIC results were interpreted using the US FDA tigecycline susceptibility breakpoints for Enterobacteriaceae (susceptible [S] or=8 microg/mL). The disk diffusion results were interpreted by criteria recommended by Jones et al. (S >or=16 mm; I 13-15 mm; R or=19 mm; I 15-18 mm; R

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Humans; Microbial Sensitivity Tests; Minocycline; Taiwan; Tigecycline

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cross Infection; Drug Resistance, Bacterial; Enteritis; Feces; Hematologic Diseases; Humans; Minocycline; Sputum; Tigecycline

The study was performed to detect the in vitro activity of tigecycline in multidrug-resistant Acinetobacter isolates from patients in Hacettepe University Adult Hospital, Turkey. The microorganisms were isolated from clinical specimens of patients with respiratory and bloodstream infections. Thirty (66.7%) of the 45 inpatients were in ICUs. In vitro activity of imipenem, meropenem, ceftazidime, ciprofloxacin and aztreonam in 124 Acinetobacter species isolated was evaluated by microdilution test. Overall, 51 (41%) Acinetobacter spp. were found to be resistant to > or = 3 antibiotics belonging to different antimicrobial classes and defined as multidrug-resistant (MDR). Among the MDR Acinetobacter spp. 32 (62.7%) were Acinetobacter baumannii and 19 (37.3%) Acinetobacter lwoffii. In vitro activity of tigecycline against MDR isolates were studied by E-test. Each MDR isolate was also tested for metallo-beta-lactamase (MBL) production using CLSI guidelines. Forty-five (88.2%) of the isolates were found to produce MBL. The MIC90s of all antimicrobial agents tested except tigecycline were > or = 64 microg/ml whereas the MIC50, and MIC90 of tigecycline were found 1 microg/ml and 1.5 microg/ml, respectively. ERIC-PCR results revealed that bloodstream and respiratory isolates had nine and six different patterns, respectively. In conclusion, tigecycline has been shown to have potent in vitro activity against MDR Acinetobacter spp. and might be of therapeutic value in the treatment of infections due to MDR Acinetobacter spp., including those harbouring MBLs. Further clinical trials are needed to confirm the efficacy of tigecycline in the management of MDR Acinetobacter infections.

Topics: Acinetobacter; Acinetobacter Infections; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Microbial Sensitivity Tests; Minocycline; Tigecycline

In a recent multi-centre Italian survey (2003-2004), conducted in 45 laboratories throughout Italy with the aim of monitoring microorganisms responsible for severe infections and their antibiotic resistance, Acinetobacter baumannii was isolated from various wards of 9 hospitals as one of the most frequent pathogens. One hundred and seven clinically significant strains of A. baumannii isolates were included in this study to determine the in vitro activity of tigecycline and comparator agents.. Tests for the susceptibility to antibiotics were performed by the broth microdilution method as recommended by CLSI guidelines. The following antibiotics were tested: aztreonam, piperacillin/tazobactam, ampicillin/sulbactam, ceftazidime, cefepime, imipenem, meropenem tetracycline, doxycycline, tigecycline, gentamicin, amikacin, ciprofloxacin, colistin, and trimethoprim/sulphametoxazole. The PCR assay was used to determine the presence of OXA, VIM, or IMP genes in the carbapenem resistant strains.. A. baumannii showed widespread resistance to ceftazidime, ciprofloxacin and aztreonam in more than 90% of the strains; resistance to imipenem and meropenem was 50 and 59% respectively, amikacin and gentamicin were both active against about 30% of the strains and colistin about 99%, with only one strain resistant. By comparison with tetracyclines, tigecycline and doxycycline showed a higher activity. In particular, tigecycline showed a MIC90 value of 2 mg/L and our strains displayed a unimodal distribution of susceptibility being indistinctly active against carbapenem-susceptible and resistant strains, these latter possessed OXA-type variant enzymes.. In conclusion, tigecycline had a good activity against the MDR A. baumannii strains while maintaining the same MIC(90) of 2 mg/L against the carbapenem-resistant strains.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; DNA, Bacterial; Drug Resistance, Bacterial; Humans; Italy; Microbial Sensitivity Tests; Minocycline; Polymerase Chain Reaction; Tigecycline

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Humans; Iraq; Male; Middle Aged; Minocycline; Osteomyelitis; Tigecycline; Vancomycin

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

Topics: Acinetobacter baumannii; Acinetobacter Infections; Humans; Minocycline; Tigecycline

The susceptibilities of 142 Acinetobacter baumannii-calcoaceticus complex isolates (95 from wounded U.S. soldiers deployed overseas) to 13 antimicrobial agents were determined by broth microdilution. The most active antimicrobial agents (> or =95% of isolates susceptible) were colistin, polymyxin B, and minocycline.

Topics: Acinetobacter; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Military Personnel; Minocycline; Polymyxin B; United States; Warfare

Carbapenem resistance in Acinetobacter spp. is an emerging problem in China. We investigated the molecular epidemiology and carbapenemase genes of 221 nonrepetitive imipenem-resistant clinical isolates of Acinetobacter spp. collected from 1999 to 2005 at 11 teaching hospitals in China. Genotyping by pulsed-field gel electrophoresis (PFGE) found 15 PFGE patterns. Of these, one (clone P) was identified at four hospitals in Beijing and another (clone A) at four geographically disparate cities. Most imipenem-resistant isolates exhibited high-level resistance to all beta-lactams and were only susceptible to colistin. bla(OXA-23)-like genes were found in 97.7% of isolates. Sequencing performed on 60 representative isolates confirmed the presence of the bla(OXA-23) carbapenemase gene. Analysis of the genetic context of bla(OXA-23) showed the presence of ISAba1 upstream of bla(OXA-23). All of the 187 A. baumannii isolates identified by amplified RNA gene restriction analysis carried a bla(OXA-51)-like oxacillinase gene, while this gene was absent from isolates of other species. Sequencing indicated the presence of bla(OXA-66) for 18 representative isolates. Seven isolates of one clone (clone T) carried the plasmid-mediated bla(OXA-58) carbapenemase gene, while one isolate of another clone (clone L) carried the bla(OXA-72) carbapenemase gene. Only 1 isolate of clone Q carried the bla(IMP-8) metallo-beta-lactamase gene, located in a class 1 integron. Of 221 isolates, 77.8% carried bla(PER-1)-like genes. Eleven different structures of class 1 integrons were detected, and most integrons carried genes mediating resistance to aminoglycosides, rifampin, and chloramphenicol. These findings indicated clonal spread of imipenem-resistant Acinetobacter spp. and wide dissemination of the OXA-23 carbapenemase in China.

Topics: Acinetobacter; Acinetobacter Infections; Aminoglycosides; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; beta-Lactams; Blotting, Southern; Carbapenems; China; Chloramphenicol; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Hospitals; Humans; Imipenem; Integrons; Microbial Sensitivity Tests; Molecular Epidemiology; Molecular Sequence Data; Rifampin; Sequence Analysis, DNA

Acinetobacter sp. isolates having multidrug resistance (MDR) patterns have become common in many medical centers worldwide, limiting therapeutic options. A five-center study tested 103 contemporary clinical Acinetobacter spp., including MDR strains, by reference broth microdilution and disk diffusion (15-mug disk content) methods against tigecycline. Applying U.S. Food and Drug Administration tigecycline breakpoint criteria for Enterobacteriaceae (susceptibility at < or =2 microg/ml [< or =1 microg/ml by the European Committee on Antimicrobial Susceptibility Testing]; disk diffusion breakpoints at > or =19 mm and < or =14 mm) to Acinetobacter spp. led to an unacceptable error rate (23.3%). However, an adjustment of tigecycline disk diffusion breakpoints (susceptible/resistant) to > or =16/ < or =12 mm reduced intermethod errors to an acceptable level (only 9.7%, all minor).

Topics: Acinetobacter; Acinetobacter Infections; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

Multidrug-resistant (MDR) Acinetobacter baumannii is increasing in our hospital and worldwide, raising the necessity of finding effective therapies. We aimed to evaluate the in vitro activity of tigecycline against MDR A. baumannii clones isolated before tigecycline was used in our institution.. Eighty-two unique patient clinical isolates of multidrug-resistant A. baumannii collected in 2003 were studied. Species identification and antibiotic susceptibilities were determined by Vitek-2. Tigecycline MIC was determined by Etest. Clonal relatedness was determined by PFGE.. MDR A. baumannii possessed 19 different pulsotypes. Sixty-six percent of the isolates were resistant to tigecycline, 12% were intermediate and 22% were susceptible. The MIC(50) and MIC(90) of tigecycline were 16 and 32 mg/L, respectively, with a wide MIC range of 1-128 mg/L. Variability in MIC of tigecycline was evident between and within the same pulsotype.. We report here high resistance rates to tigecycline, and higher than previously described MICs, in multiple clones of MDR A. baumannii. As tigecycline represents a new treatment choice for infections caused by A. baumannii, these findings are worrisome.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Tetracycline Resistance; Tigecycline

Topics: Acinetobacter Infections; Anti-Bacterial Agents; Australia; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Tetracycline Resistance; Tigecycline

To investigate the role of the AdeABC multidrug efflux pump in the decreased susceptibility of clinical isolates of Acinetobacter calcoaceticus-Acinetobacter baumannii complex to tigecycline.. Gene expression was analysed by Taqman RT-PCR. A single cross-over achieved insertional inactivation of the adeB gene with a suicide plasmid construct carrying an adeB fragment obtained by PCR. Analysis of the adeRS locus was performed by PCR and sequencing. Ribotyping was performed with the RiboPrinter system. MICs were determined by Etest.. Expression analysis revealed constitutive overexpression of adeABC in less-susceptible clinical isolates G5139 and G5140 (tigecycline MIC=4 mg/L) when compared with the isogenic clinical isolates G4904 and G5141 (MIC=1.5 mg/L). Insertional mutants GC7945 (adeB knockout in G5139) and GC7951 (adeB knockout in G5140) were obtained, which resulted in tigecycline MICs of 0.5 mg/L. As reported previously, the expression of adeABC is regulated by the two-component signalling system encoded by the adeR and adeS genes. PCR and sequencing analyses revealed an insertion of an IS(ABA-1) element in the adeS gene of G5139 and G5140.. The results of this study suggest that decreased susceptibility to tigecycline in the A. calcoaceticus-A. baumannii complex is associated with the overexpression of the AdeABC multidrug efflux pump.

Topics: Acinetobacter baumannii; Acinetobacter calcoaceticus; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; DNA, Bacterial; DNA, Ribosomal; Drug Resistance, Bacterial; Membrane Transport Proteins; Minocycline; Ribotyping; RNA, Ribosomal, 16S; Tigecycline

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cross Infection; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

The study investigated the effect of colistin and minocycline when tested singly and in combination against Acinetobacter baumannii.. Thirteen unrelated imipenem-resistant A. baumannii clinical isolates were included in the study. MICs of colistin sulphate and minocycline were determined by broth macrodilution and Etest. Organisms were also tested against the two antibiotics singly and in combination using time-kill methods and an Etest-based method.. Neither colistin nor minocycline when tested alone demonstrated bactericidal activity. However, the combination of colistin and minocycline demonstrated bactericidal activity against most of the isolates tested. At 24 h, the combination of antibiotics demonstrated synergy in 12 of the 13 isolates by time-kill methods. None of the isolates demonstrated synergy by Etest methods.. The combination of colistin and minocycline was found to be bactericidal and synergistic against A. baumannii by time-kill methods. There was no agreement between time-kill and Etest methods for synergy testing.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Imipenem; Microbial Sensitivity Tests; Minocycline

To determine the in vitro activities and interactions of imipenem, colistin and tigecycline with old antibacterial agents against carbapenem-resistant Acinetobacter baumannii.. Forty-three carbapenem-resistant A. baumannii isolates from the intensive care unit of a university hospital were collected and their MICs of imipenem, colistin and tigecycline were determined. With eight randomly selected carbapenem-resistant isolates, an in vitro time-kill study was performed for the evaluation of antibacterial activity of colistin, tigecycline, imipenem/sulbactam and colistin/rifampicin.. The time-kill study of colistin demonstrated bactericidal activity against A. baumannii at concentrations of 4xMIC and 8xMIC, whereas tigecycline showed bacteriostatic activity at all concentrations. The combination regimens of imipenem/sulbactam and colistin/rifampicin were synergistic and bactericidal at 1xMIC.. Imipenem/sulbactam combination, colistin and tigecycline showed good in vitro activities against carbapenem-resistant A. baumannii isolates. Even though colistin is bactericidal against carbapenem-resistant A. baumannii, the colistin/rifampicin combination is more warranted in order to be certain.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Colistin; Colony Count, Microbial; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Reverse Transcriptase Polymerase Chain Reaction; Rifampin; Sulbactam; Tigecycline

Topics: Acinetobacter; Acinetobacter Infections; Anti-Bacterial Agents; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

Topics: Acinetobacter; Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Argentina; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

To evaluate early experience with tigecycline alone or in combination with other antimicrobials for treatment of ventilator-associated pneumonia (VAP) and/or bacteremia caused by multidrug-resistant Acinetobacter baumannii.. Retrospective case series.. University-affiliated medical center.. Twenty-five patients with multidrug-resistant A. baumannii who received tigecycline for VAP (19 patients), bacteremia (3), or VAP plus bacteremia (3) between September 1, 2005, and May 31, 2006. Five patients were treated with tigecycline alone.. Primary outcomes were resolution of clinical signs and symptoms of the infection and documented microbial eradication of A. baumannii with tigecycline. Overall, 21 (84%) of the 25 patients had clinical resolution. Four had clinical failure: three with VAP and one with VAP plus bacteremia that developed resistance to tigecycline during therapy. Microbial eradication was demonstrated in 12 (80%) of 15 patients in whom repeat cultures were obtained. Three patients with VAP had a recurrence of infection: one patient had two recurrences, and two patients had one recurrence each. All four recurrent episodes led to clinical resolution and microbial eradication. No patients discontinued tigecycline because of adverse events.. Tigecycline was effective in most of these 25 patients when used alone or in combination with other antimicrobials for VAP and/or bacteremia caused by multidrug-resistant A. baumannii. The emergence of a resistant strain while one patient was receiving therapy, however, is concerning.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; Bacteremia; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Ventilator-Associated; Tigecycline

A 53-year-old woman experienced a multidrug-resistant (MDR) Acinetobacter baumannii urinary tract infection 5 months after undergoing kidney and liver transplantation. The tigecycline minimum inhibitory concentration (MIC) for her A. baumannii isolate was 1.5 microg/ml; the patient received 2 weeks of therapy with intravenous tigecycline as a 100-mg loading dose followed by 50 mg every 12 hours, with no lapses in treatment and with resolution of the infection. Three weeks later, MDR A. baumannii was isolated from her sputum in the setting of clinical evidence of pneumonia, and tigecycline was restarted; the tigecycline MIC for the A. baumannii isolate was 2 microg/ml. At approximately the same time, the patient was found to have a paraspinal abscess and spinal osteomyelitis. Cultures of the abscess fluid grew A. baumannii with a tigecycline MIC of 24 microg/ml. A follow-up sputum culture again yielded A. baumannii, but with a tigecycline MIC of 24 microg/ml. Urine culture at that time also grew A. baumannii with a tigecycline MIC of 24 microg/ml. Clinicians should be aware that tigecycline MICs for A. baumannii isolates may increase during therapy with tigecycline after only brief exposure to the drug. Patients receiving tigecycline for Acinetobacter should be monitored for the development of clinical resistance, and isolates should be monitored for evidence of microbiologic resistance.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Drug Resistance, Bacterial; Female; Humans; Kidney Transplantation; Liver Transplantation; Microbial Sensitivity Tests; Middle Aged; Minocycline; Osteomyelitis; Pneumonia, Bacterial; Spinal Diseases; Tetracycline Resistance; Tigecycline; Urinary Tract Infections

We report a case of pulmonary and bloodstream infection due to multiresistant Acinetobacter baumannii six days after a severe trauma. Clinical condition transiently improved following antimicrobial treatment with ticarcillin-clavulanate and rifampicin. However, a septic shock developed on the fourth day due to the emergence of a strain only sensible to cotrimoxazole, colistin and tigecycline. Cure was achieved after a two week treatment with piperacillin-tazobactam, cotrimoxazole and tigecycline. This case shows that combined antimicrobial therapy including tigecycline can be relevant in some severe pulmonary infections due to multiresistant A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Anti-Bacterial Agents; Anti-Infective Agents; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Minocycline; Penicillanic Acid; Piperacillin; Shock, Septic; Tazobactam; Tigecycline; Trimethoprim, Sulfamethoxazole Drug Combination

Reported here is the case of a patient with septic shock due to multidrug-resistant Acinetobacter baumannii, which developed after complicated acute pancreatitis with intra-abdominal abscess. Treatment with colistin methanesulphonate and high doses of meropenem were initiated, but since shock persisted, tigecycline was added to the regimen, resulting in successful resolution of the infection.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Male; Meropenem; Minocycline; Pancreatitis, Acute Necrotizing; Shock, Septic; Thienamycins; Tigecycline; Treatment Outcome

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactam Resistance; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

In vitro activity of tigecycline against 148 strains of Acinetobacter baumannii isolated from different patients hospitalized at Siriraj Hospital, Bangkok, Thailand during 2002 to 2005 was conducted. These isolates were resistant to beta-lactams, aminoglycosides and fluoroquinolones. In vitro susceptibilities were determined by Kirby-Bauer disk diffusion, E-test and broth microdilution methods. The MIC50 and MIC90 values of tigecycline against A. baumannii determined by the broth microdilution method were 0.5 and 1 mg/L respectively. The MICs of tigecycline determined by E-test were 4-fold higher than those from the broth microdilution method. An inhibition zone of > or = 13 mm was well correlated with a tigecycline MIC of < or = 2 mg/L and had a sensitivity of 99% and a specificity of 100%. The study results indicated that 97.3% of MDR A. baumannii strains isolated from the patients hospitalized at Siriraj Hospital were susceptible to tigecycline. Tigecycline may prove to be an important antibiotic for treatment of multidrug-resistant A. baumannii infections in Thailand in the near future.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Drug Resistance, Bacterial; In Vitro Techniques; Minocycline; Thailand; Tigecycline

The presence of tetracycline (TET) resistance genes was investigated in 49 genotypically related and unrelated multidrug-resistant Acinetobacter baumannii (MDRAB) strains from European hospitals including representatives of pan-European clones I and II. Except for one strain, all MDRAB strains displayed resistance to tetracycline (MIC range of 16 to > 512 microg/ml) but were susceptible (MIC < 4 microg/ml) or exhibited intermediate resistance (MIC of 4-8 microg/ml) to minocycline (MIN). In 37 strains, either tet(A) or tet(B) was detected and one of these strains possessed both tet(A) and tet(M). In addition, all MDRAB strains contained the aspecific efflux gene adeB irrespectively of whether they harbored tet genes or not. Repetitive DNA element (rep)-PCR fingerprinting using the (GTG)5 primer [(GTG)5-PCR] revealed that strains previously assigned to pan-European clones I and II were grouped into two separate clusters. In addition, these clusters also contained strains that had not been typed previously, indicating that (GTG)5-PCR is a valuable method for recognizing putative new members of MDRAB clones. Most, but not all, members of clones I and II were linked to the presence of either tet(A) or tet(B) and displayed different levels of TET resistance with MIC values of 32 to > 512 microg/ml and > 512 microg/ml, respectively. Of these two genes only tet(B) encodes an efflux of both TET and MIN, which was reflected by the relatively high MIC values for MIN (4 microg/ml) shown by the majority of the tet(B)-carrying clone II strains as opposed to the low MIC values for MIN (< 1 microg/ml) displayed by most tet(A)-containing clone I strains. Collectively, our phenotypic and genotypic resistance data support the therapeutic evaluation of second-generation tetracyclines like MIN as promising agents for treating MDRAB infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Antiporters; Bacterial Proteins; Cluster Analysis; DNA Fingerprinting; DNA Restriction Enzymes; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Humans; Membrane Transport Proteins; Microbial Sensitivity Tests; Minocycline; Polymerase Chain Reaction; Repetitive Sequences, Nucleic Acid; Tetracycline; Tetracycline Resistance

To report the use of tetracyclines for the treatment of multidrug-resistant Acinetobacter baumannii ventilator-associated pneumonia (VAP).. Observational case series.. . The Presley Regional Trauma Center located within the Regional Medical Center, Memphis, Tennessee, USA.. Seven critically ill trauma patients with VAP caused by A. baumannii isolates that were resistant to all antibiotics tested except for doxycycline or minocycline.. Patients were treated with IV doxycycline or minocycline for an average of 13.5 (range 9-20) days.. Doxycycline or minocycline was successful in six of seven patients.. Doxycycline or minocycline may be effective for treating multidrug-resistant A. baumannii VAP.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Anti-Bacterial Agents; APACHE; Bronchoalveolar Lavage Fluid; Critical Care; Critical Illness; Cross Infection; Doxycycline; Drug Resistance, Multiple, Bacterial; Humans; Infection Control; Infusions, Intravenous; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Bacterial; Respiration, Artificial; Retrospective Studies; Tennessee; Trauma Centers; Treatment Outcome

A survey was conducted of the antimicrobial susceptibilities of 595 Acinetobacter spp. isolated from routine clinical specimens in 54 sentinel laboratories throughout the UK during 2000. Isolates of the Acinetobacter baumannii complex (genomic groups 2, 3 and 13TU; n = 443) were distinguished from other genomic groups (n = 152) by PCR fingerprinting of tDNA spacer regions. MICs of amikacin, cefotaxime, ceftazidime, ciprofloxacin, colistin, gentamicin, imipenem, meropenem, minocycline, piperacillin, piperacillin/tazobactam, rifampicin, sulbactam and tetracycline were determined on IsoSensitest agar and interpreted, wherever possible, using BSAC breakpoints. Tigecycline (GAR-936), a new glycylcycline, was also tested. Resistance to cephalosporins, aminoglycosides and ciprofloxacin was widespread, but carbapenems, colistin, sulbactam, minocycline and tigecycline were each active against >80% of the isolates. Isolates of A. baumannii were more often resistant to cefotaxime, ceftazidime, piperacillin, piperacillin/tazobactam, ciprofloxacin, gentamicin and tetracyclines than those belonging to other genomic groups, but were less often resistant to colistin; no significant differences between genomic groups were noted in the susceptibilities to amikacin, carbapenems, rifampicin or sulbactam. The relative activities of the tetracyclines were minocycline > tigecycline > tetracycline. Thirteen carbapenem-resistant isolates (MICs > or =8 mg/L; 2.2%) were received from six centres; four centres sent single isolates; one sent three and one sent six. An allele of bla(IMP) was detected in one of these isolates, but the other 12 isolates either had carbapenemase-independent resistance, or undetectable carbapenemase activity combined with other resistance mechanisms. In conclusion, carbapenems, colistin and minocycline retained greatest activity against the Acinetobacter isolates collected. Tigecycline was less active than minocycline, but both agents overcame most tetracycline resistance.

Topics: Acinetobacter; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Drug Resistance, Bacterial; Genome, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline; United Kingdom

Topics: Acinetobacter; Acinetobacter Infections; Doxycycline; Drug Resistance, Microbial; Female; Humans; Male; Middle Aged; Minocycline

Acinetobacter calcoaceticus (Mima polymorpha) is not a well known organism, and its identification can be confusing due to its variable morphology and sensitivity pattern. In a joint infection, delay in identification or appropriate treatment can result in added morbidity. An A. calcoaceticus (Mima) infection in the hand seems not to have been previously reported. The present case involving a finger joint infection illustrates the pathogenicity of A. calcoaceticus (Mima) and problems of treatment. Minocycline is recommended as the drug of choice in subsequent A. calcoaceticus (Mima) and (Herella) infections.

Topics: Acinetobacter; Acinetobacter Infections; Hand Injuries; Humans; Male; Middle Aged; Minocycline

Two patients had community-acquired Acinetobacter calcoaceticus var anitratus pneumonia. Both patients were alcoholic and one was cirrhotic. One patient died and the other received two weeks of gentamicin therapy and survived. Misinterpretation of the sputum Gram stain delayed diagnosis and institution of proper therapy in both cases. In addition to organisms sensitive to penicillins such as Neisseria or Haemophilus, Acinetobacter must be considered in the differential diagnosis of community-acquired Gram-negative coccobacillary pneumonia.

Topics: Acinetobacter; Acinetobacter Infections; Adult; Alcoholism; Amikacin; Diagnostic Errors; Drug Resistance, Microbial; Female; Gentamicins; Humans; Liver Cirrhosis; Male; Middle Aged; Minocycline; Pneumonia; Sputum; Staining and Labeling; Tobramycin