minocycline and Enterobacteriaceae-Infections

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

Adequate management of severely ill patients with secondary peritonitis requires supportive therapy of organ dysfunction, source control of infection and antimicrobial therapy. Since secondary peritonitis is polymicrobial, appropriate empiric therapy requires combination therapy in order to achieve the needed coverage for both common and more unusual organisms. This article reviews etiological agents, resistance mechanisms and their prevalence, how and when to cover them and guidelines for treatment in the literature. Local surveillances are the basis for the selection of compounds in antibiotic regimens, which should be further adapted to the increasing number of patients with risk factors for resistance (clinical setting, comorbidities, previous antibiotic treatments, previous colonization, severity…). Inadequate antimicrobial regimens are strongly associated with unfavorable outcomes. Awareness of resistance epidemiology and of clinical consequences of inadequate therapy against resistant bacteria is crucial for clinicians treating secondary peritonitis, with delicate balance between optimization of empirical therapy (improving outcomes) and antimicrobial overuse (increasing resistance emergence).

Topics: Abdominal Cavity; Anti-Bacterial Agents; Candida; Candidiasis; Carbapenems; Critical Illness; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Fluoroquinolones; Humans; Microbial Sensitivity Tests; Minocycline; Peritonitis; Practice Guidelines as Topic; Risk Factors; Tigecycline

Carbapenem-resistant Enterobacteriaceae (CRE) infections are prevalent worldwide; they have few effective treatments and this jeopardizes public health. Clinicians often use tigecycline to combat CRE, but its clinical efficacy remains controversial. Therefore, to compare the efficacy and safety of tigecycline in treating CRE infections compared with that of other antimicrobial agents, and to evaluate whether combination therapy and high-dose regimens are beneficial, we performed a systematic review and meta-analysis. PubMed and Embase were searched for controlled trials or cohort studies reporting the efficacy and/or safety of tigecycline-based regimens to treat CRE infections. Statistical analyses were performed using the Comprehensive Meta-Analysis V2.2. All meta-analyses were performed based on fixed- or random-effects model, and the I method was used to assess heterogeneity. Twenty-one controlled studies and 5 single-arm studies were included in this systematic review. With regard to the controlled studies, the tigecycline groups did not differ significantly from the control groups in terms of overall mortality (Odds ratio (OR) = 0.96 [95% confidence interval (CI) = 0.75-1.22; P = 0.73]), clinical response rate (OR = 0.58 [95% CI = 0.31-1.09; P = 0.09]), or microbiological response rate (OR = 0.46 [95% CI = 0.15-1.44; P = 0.18]). Subgroup analyses showed that 30-day mortality was significantly lower in patients who received tigecycline combination therapy than in those who received monotherapy (OR = 1.83 [95% CI = 1.07-3.12; P = 0.03]) and other antibiotic regimens (OR = 0.59 [95% CI = 0.39-0.88; P = 0.01]), respectively. In addition, high-dose tigecycline regimens differed significantly from standard dose schedules in terms of ICU mortality (OR = 12.48 [95% CI = 2.06-75.43; P = 0.006]). The results of the 5 single-arm studies corroborated the findings of the controlled studies. Our results indicated that the efficacy of tigecycline in treating CRE infections is similar to that of other antibiotics. Tigecycline combination therapy and high-dose regimens may be more effective than monotherapy and standard-dose regimens, respectively. Nonetheless, considering that the current available evidence is limited, well-designed randomized controlled trials are urgently needed to clarify the comparative efficacy of tigecycline in treating CRE infections.

Topics: Anti-Bacterial Agents; Carbapenems; Drug Resistance, Bacterial; Drug Therapy, Combination; Enterobacteriaceae Infections; Humans; Minocycline; Tigecycline

Carbapenem-resistant Enterobacteriaceae (CRE) are associated with a high mortality rate and are an increasing problem worldwide. In this mini-review, we consider the growing number of observational studies in favour of combination therapy but highlight the absence of randomised control trials. We discuss the importance of data on minimum inhibitory concentrations (MICs), both for surveillance and for individual patient management. We examine the issues surrounding the use of carbapenems, polymyxins and tigecycline in the treatment of CRE. When and how should we be using carbapenems? Which polymyxin is best? Is tigecycline much maligned? Further studies are urgently needed to validate drug combinations, doses and ratios to maximise efficacy whilst reducing drug exposure and adverse effects.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenems; Case Management; Drug Therapy, Combination; Enterobacteriaceae; Enterobacteriaceae Infections; Epidemiological Monitoring; Humans; Microbial Sensitivity Tests; Minocycline; Observational Studies as Topic; Polymyxins; Randomized Controlled Trials as Topic; Tigecycline; Treatment Outcome

Raoultella planticola has been considered a relatively harmless Gram-negative bacteria, rarely associated with clinical infection. However, in recent years, the frequency at which severe infection by R. planticola and drug-resistant strains are reported in literature has increased. Here, we present one case of acute cholecystitis caused by R. planticola, and review all previously reported cases of the infection in an attempt to identify new trends in biological and clinical features of R. planticola infections.

Topics: Abdominal Pain; Aged; Aged, 80 and over; Alcoholism; Anti-Bacterial Agents; Cholecystitis, Acute; Communicable Diseases, Emerging; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Male; Middle Aged; Minocycline; Tigecycline

To address the therapeutic management of carbapenem-resistant Enterobacteriaceae on the basis of literature of the last 12 months.. Retrospective and prospective (nonrandomized noncontrolled) studies provide data regarding the management of infections due to carbapenem-resistant Enterobacteriaceae. The combination of a carbapenem with colistin or high-dose tigecycline or aminoglycoside or even triple carbapenem-containing combinations if the minimum inhibitory concentration (MIC) range of carbapenem (meropenem and imipenem) resistance is 8 mg/l or less seems to have an advantage over monotherapy with either colistin or tigecycline or fosfomycin. For Enterobacteriaceae with MIC for carbapenems over 8 mg/l, combination regimens involve colistin, tigecycline usually administered in a double dose than that suggested by its manufacturer, fosfomycin and aminoglycosides in various combinations.. Suggestions based on the limited literature cannot be made safely. Combination regimens involving carbapenems for Enterobacteriaceae with MICs 8 mg/l or less for carbapenems (in dual combination with colistin or high-dose tigecycline or aminoglycoside or even triple combinations) seem to confer some therapeutic advantage over monotherapy. For Enterobacteriaceae with higher than the above-mentioned MICs, a combination of two or even three antibiotics among colistin, high-dose tigecycline, aminoglycoside and fosfomycin seems to confer decreased mortality.

Topics: beta-Lactam Resistance; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Enterobacteriaceae Infections; Humans; Infection Control; Klebsiella pneumoniae; Microbial Sensitivity Tests; Minocycline; Practice Patterns, Physicians'; Prospective Studies; Retrospective Studies; Tigecycline; Treatment Outcome

The emergence of carbapenem-resistant Enterobacteriaceae (CRE) highlights the importance of effective antibiotics to maintain the safety of our health care system. Clinicians will encounter CRE as a cause of difficult-to-treat and often fatal infections in hospitalized patients. We review the mechanisms of carbapenem resistance, the dissemination and clinical impact of these resistant organisms, and challenges to their detection, treatment, and control.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenems; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Klebsiella pneumoniae; Minocycline; 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

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

Antimicrobial drug resistance is spreading among Enterobacteriaceae, limiting the utility of traditionally used agents. We sought to systematically review the microbiological activity and clinical effectiveness of tigecycline for multidrug-resistant (MDR) Enterobacteriaceae, including those resistant to broad-spectrum beta-lactams due to the expression of extended-spectrum beta-lactamases (ESBLs), AmpC enzymes and carbapenemases (including metallo-beta-lactamases).. PubMed was searched for articles including relevant data.. Twenty-six microbiological and 10 clinical studies were identified. Tigecycline was active against more than 99% of 1936 Escherichia coli isolates characterized by any of the above resistance patterns (including 1636 ESBL-producing isolates) using the US Food and Drug Administration (FDA) breakpoint of susceptibility (MIC < or = 2 mg/L). Findings were not different using the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoint (< or = 1 mg/L). Susceptibility rates for Klebsiella spp. with any of the above resistance patterns were 91.2% for 2627 isolates by the FDA criteria and 72.3% for 1504 isolates by the EUCAST criteria (92.3% for 2030 and 72.3% for 1284 ESBL-producing isolates, by the FDA and EUCAST criteria, respectively). The degree of microbiological activity of tigecycline against 576 MDR Enterobacter spp. isolates was moderate. In clinical studies, 69.7% of the 33 reported patients treated with tigecycline achieved resolution of an infection caused by a carbapenem-resistant or ESBL-producing or MDR Enterobacteriaceae.. Tigecycline is microbiologically active against almost all of the ESBL or MDR E. coli isolates and the great majority of ESBL or MDR Klebsiella spp. isolates. Further evaluation of its clinical utility against such resistant Enterobacteriaceae, particularly regarding non-labelled indications, is warranted.

Topics: Anti-Bacterial Agents; beta-Lactamases; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Minocycline; Tigecycline; Treatment Outcome; United States

The progressive increase of extended-spectrum beta-lactamase (ESBL) -producing enteric bacteria in recent years has called for a re-evaluation of current antibiotic therapy for these infections. The activity and potential use of two old antimicrobials, nitrofurantoin and fosfomycin, and the new compound tigecycline for treatment of infections due to ESBL-producing Enterobacteriaceae, with special emphasis on E. coli, are reviewed. Fosfomycin continues to be active against the most common uropathogens; in a recent survey from Spain, among the 428 ESBL-producing isolates, the resistance rate of E. coli to fosfomycin was 0.3%, whereas the resistance rate of K. pneumoniae was 7.2%. Other recent surveys, from other parts of the world, confirm the activity of fosfomycin against ESBL-producing E. coli. The rate of resistance to nitrofurantoin in recent surveys in the USA and Canada was 1.1% among 1142 isolates of E. coli from outpatient urinary isolates. However, among 115 clinical isolates of E. coli ESBL producers, only 71.3% were sensitive to nitrofurantoin. Also, E. coli resistance to nitrofurantoin has been reported to be high in a recent survey in Latin American hospitals and in Italy. Tigecycline is a glycylcycline that circumvents efflux and ribosomal protection, the two most frequent genetic mechanisms of tetracycline resistance. The recent activity of tigecycline against 285 nonclonally related isolates expressing well-characterised ESBLs from hospital settings and the community reveal susceptibility rates for tigecycline of 97.5%. Because responses to nitrofurantoin may be less satisfactory and may require longer courses of therapy, nitrofurantoin is considered to be an alternative, rather than a first-line, therapeutic agent for this clinical syndrome. Fosfomycin trometamol is a safe and effective alternative for the treatment of cystitis and asymptomatic UTI during pregnancy, and has become, in many countries, the first choice for treatment of any type of cystitis. Finally, for treatment of systemic infections in the hospital setting, tigecycline could be an option that would reduce selection for ESBL-producing organisms.

Topics: Anti-Bacterial Agents; beta-Lactamases; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Fosfomycin; Microbial Sensitivity Tests; Minocycline; Nitrofurantoin; Tigecycline

Patients with intra-abdominal infections differ with regard to the type of infection and the severity of illness. However, the impact of these factors, together with differences in drug exposure, on clinical response is not well understood. Using phase 2 and 3 data for patients with complicated intra-abdominal infections, the relative importance of tigecycline exposure, host factors, and disease factors, alone or in combination, for the probability of clinical response was examined. Patients with complicated intra-abdominal infections who received tigecycline intravenously as a 100-mg loading dose followed by 50 mg every 12 h for 5 to 14 days and who had adequate clinical, pharmacokinetic, and response data were evaluated. Multivariable logistic regression was used to identify factors associated with clinical response. A final multivariable logistic regression model demonstrated six factors based on 123 patients to be predictive of clinical success: a weight of <94 kg (P = 0.026), the absence of Pseudomonas aeruginosa in baseline cultures (P = 0.021), an APACHE II score of <13 (P = 0.029), non-Hispanic race (P = 0.005), complicated appendicitis or cholecystitis (P = 0.004), and a ratio of the area under the concentration-time curve (AUC) to the MIC (AUC/MIC ratio) of > or =3.1 (P = 0.003). The average model-predicted probability of clinical success when one unfavorable factor was present was 0.940. This probability was lower (0.855) when the AUC/MIC ratio was < 3.1 and the remaining five factors were set to the favorable condition. The average model-predicted probability of clinical success in the presence of two unfavorable factors was 0.594. These findings demonstrated the impact of individual and multiple factors on clinical response in the context of drug exposure.

Topics: Abdominal Cavity; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Area Under Curve; Bacteria, Anaerobic; Bacterial Infections; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Predictive Value of Tests; Tigecycline; Treatment Outcome; Young Adult

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

The global emergence of carbapenem-resistant Enterobacteriaceae (CRE) presents a significant clinical concern, prompting the WHO to prioritize CRE as a top priority pathogen in their 2017 global antibiotic-resistant bacteria priority list. Due to the fast-depleting antibiotic arsenal, clinicians are now resorting to using once-abandoned, highly toxic antibiotics such as the polymyxins and aminoglycosides, creating an urgent need for new antibiotics. Drug repurposing, the application of an approved drug for a new therapeutic indication, is deemed a plausible solution to this problem. A total of 1,163 FDA-approved drugs were screened for activity against a clinical carbapenem- and multidrug-resistant E. coli isolate using a single-point 10 μM assay. Hit compounds were then assessed for their suitability for repurposing. The lead candidate was then tested against a panel of clinical CREs, a bactericidal/static determination assay, a time-kill assay and a checkerboard assay to evaluate its suitability for use in combination with Tigecycline against CRE infections. Three drugs were identified. The lead candidate was determined to be Zidovudine (azidothymidine/AZT), an oral anti-viral drug used for HIV treatment. Zidovudine was shown to be the most promising candidate for use in combination with Tigecycline to treat systemic CRE infections. Further experiments should involve the use of animal infection models.

Topics: Animals; Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Drug Repositioning; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae Infections; Escherichia coli; Humans; Mice; Microbial Sensitivity Tests; Minocycline; Tigecycline; Zidovudine

We hypothesised that treatment with a tigecycline-based antimicrobial regimen for intra-abdominal infection (IAI) could be associated with lower rates of subsequent carbapenem-resistant Enterobacteriaceae (CRE) colonisation or Clostridium difficile infection (CDI) compared with a meropenem-based regimen.. We performed a retrospective, single-centre, matched (1:1) cohort analysis of all patients who received at least 5 days of empirical or targeted tigecycline (TIG)- or meropenem (MER)-based treatment regimens for IAI over a 50-month period. Patients with previous CRE colonisation and CDI were excluded. Risk factors for CRE and CDI were assessed with a Cox regression model that included treatment duration as a time-dependent variable. Thirty-day mortality was assessed with Kaplan-Meier curves.. We identified 168 TIG-treated and 168 MER-treated patients. The cumulative incidence rate ratio of CDI was 10-fold lower in TIG-treated vs. MER-treated patients (incidence rate ratio [IRR] 0.10/1000 patient-days, 95%CI 0.002-0.72, P = 0.007), but similar incidence rates were found for CRE colonisation (IRR 1.39/1000 patient-days, 95%CI 0.68-2.78, P = 0.36). In a multivariate Cox regression model, the receipt of a TIG- vs. MER-based regimen was associated with significantly lower rates of CDI (HR 0.07, 95%CI 0.03-0.71, P = 0.02), but not CRE (HR 1.12, 95% CI 0.45-2.83, P = 0.80). All-cause 30-day mortality was similar in the two groups (P = 0.46).. TIG-based regimens for IAI were associated with a 10-fold lower incidence of CDI compared with MER-based regimens, but there was no difference in the incidence of CRE colonisation.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Carrier State; Clostridioides difficile; Clostridium Infections; Enterobacteriaceae Infections; Female; Humans; Incidence; Intraabdominal Infections; Male; Meropenem; Middle Aged; Minocycline; Retrospective Studies; Risk Factors; Survival Analysis; Thienamycins; Tigecycline; Young Adult

A set of 908 clinically derived colistin-resistant Enterobacteriaeae isolates collected worldwide in 2014-2016 were screened for the presence of the plasmid-borne mcr-1, mcr-2, mcr-3, mcr-4 and mcr-5 genes. In total 3.2% (29/908) of the collection were positive for mcr, including 27 Escherichia coli, 1 Klebsiella pneumoniae and 1 Enterobacter cloacae. Twenty-four isolates possessed genes from the mcr-1 family, including the original mcr-1 (n = 22), as well as mcr-1.2 (n = 1) and mcr-1.5 (n = 1), which each differ from mcr-1 by encoding single amino acid variations. Genes from the mcr-3 family were found in isolates from Thailand, including mcr-3.1 (n = 3) and mcr-3.2 (n = 1). An E. coli isolated from a patient with a urinary tract infection in Colombia contained the recently discovered mcr-5. The full colistin-resistant collection was tested against a panel of antimicrobial agents with ceftazidime-avibactam and tigecycline exhibiting the highest activity.

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Bacterial Proteins; Ceftazidime; Colistin; Drug Combinations; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Epidemiological Monitoring; Humans; Internationality; Minocycline; Prevalence; Tigecycline

We examined the in vitro activity of minocycline against 103 Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae isolates and found approximately half had susceptible (26%) or intermediate (26%) MICs. For a subset of 35 isolates, susceptibility was highest to tigecycline (71% FDA vs. 20% EUCAST) followed by minocycline (14%) and then doxycycline (6%).

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Doxycycline; Enterobacteriaceae Infections; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests; Minocycline; Tigecycline

To study the evolution in the susceptibility of Enterobacter spp. in Crete, Greece from 2010 to 2015.. Non-duplicate isolates were studied using automated systems. Phenotypic confirmatory tests were applied.. A total of 939 Enterobacter isolates were included. Colistin was the most active antibiotic (97.9%) followed by imipenem (96.1%), gentamicin (95.7%), tigecycline (91.8%), cefepime (89.4%), chloramphenicol (85.8%), fosfomycin (85.5%), trimethoprim/sulfamethoxazole (83.3%) and piperacillin/tazobactam (73.3%). Antibiotic resistance did not increase during the study period for most antibiotics. Lower susceptibility was observed among multidrug-resistant strains and carbapenem-nonsusceptible isolates. AmpC was the most common resistant mechanism (21%); carbapenemases (3.7%) and aminoglycoside-modifying enzymes (6.5%) were also detected.. A significant proportion of Enterobacter spp. was resistant to several antibiotics, most notably β-lactams.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; beta-Lactams; Carbapenems; Cefepime; Cephalosporins; Child; Colistin; Drug Resistance, Multiple, Bacterial; Enterobacter; Enterobacteriaceae Infections; Greece; Hospitals, University; Humans; Microbial Sensitivity Tests; Minocycline; Penicillanic Acid; Phenotype; Piperacillin; Piperacillin, Tazobactam Drug Combination; Tigecycline

Topics: Anti-Bacterial Agents; Bacterial Proteins; Bacterial Typing Techniques; beta-Lactamases; Carbapenems; Clone Cells; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Enterobacter cloacae; Enterobacteriaceae Infections; Gene Expression Regulation, Bacterial; Humans; Microbial Sensitivity Tests; Minocycline; Multidrug Resistance-Associated Proteins; Multilocus Sequence Typing; Porins; Taiwan; Tigecycline

Topics: Aged; Amikacin; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Ciprofloxacin; Colonic Diseases; Drug Synergism; Drug Therapy, Combination; Enterobacter cloacae; Enterobacteriaceae Infections; Female; Fosfomycin; Hernia, Abdominal; Herniorrhaphy; Humans; Intestinal Fistula; Minocycline; Postoperative Complications; Prosthesis-Related Infections; Soft Tissue Infections; Surgical Mesh; Tigecycline

Raoultella planticola is a gram-negative bacterium that rarely causes diseases in humans. Here, we present a case of hospital-acquired pneumonia caused by R. planticola that likely originated in the gastrointestinal tract. To the best of our knowledge, this is the second report describing the detection of the gene New Delhi Metallo-β-lactamase-1 (bla

Topics: Aged; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Carbapenems; Cross Infection; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Enterobacteriaceae; Enterobacteriaceae Infections; Feces; Gene Expression; Humans; Levofloxacin; Male; Minocycline; Plasmids; Polymerase Chain Reaction; Sputum; Tigecycline; Treatment Outcome

We described 27 polyclonal colistin-resistant Enterobacteriaceae (MIC 4-16 μg/mL) infections (12 pneumonia, 12 urinary tract infection (UTI), two Bacteremia, and one skin/soft tissue infection) in which 74% harbored KPC. The isolates were polyclonal, 6 STs were identified and the colistin resistance was due to chromosome mutations. Eight patients with UTI received monotherapy, and combination therapy was given to 19 patients. Overall mortality was 37%. In vitro synergy using time-kill assay was observed in 14 of 19 (74%) isolates tested; the synergistic effect was observed for almost all isolates for the combination of three drugs: colistin, amikacin, and tigecycline. The Kaplan-Meier survival curve showed no significant difference comparing combination therapy with 2, 3, or more drugs and risk factors associated with death were dialysis and shock. These findings reinforce the fact that colistin in combination with other classes of drugs can be useful in treating infections caused by colistin-resistant CRE.

Topics: Amikacin; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Kaplan-Meier Estimate; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia; Prospective Studies; Soft Tissue Infections; Tigecycline; Urinary Tract Infections

To study a cohort of patients with intra-abdominal postsurgical infection treated with tigecycline to analyze its effectiveness and mortality related factors.. Prospective study of patients with intra-abdominal postsurgical infection with microbiological isolation and treated with tigecycline.. Out of 103 patients only 61 full fit inclusion criteria. Mean age was 67 year-old and 72% were male. Charlson score was ≥ 3 in 65.5%, being diabetes and colon cancer the most prevalent diseases. Cancer surgery was the most frequent procedure (n=44, 72%) and previous antibiotic administration was present in 43 cases (69%). Pitt score was ≥ 3 in 69% and most prevalent bacteria were Escherichia coli (38 %), Enterococcus spp. (34%; mainly Enterococcus faecium) and Klebsiella pneumoniae together with Enterobacter cloacae (28%). Tigecycline was prescribed alone (17; 28%) or in combination with other antibiotics (44; 72%), mainly meropenem (25; 57%) or amikacin (19, 43%). 11 patients died (18%), all of which suffered extended cancer surgery and isolation of extended-spectrum betalactamase producing Enterobacteriaceae. Factors statistically associated to death in univariate analysis were Charlson score >3, pH <7.3 and leucocyte count >20.000 cells/mm3.. As being a cohort of patients treated with tigecycline, E. faecium isolation was very frequent. Non-fatal evolution was achieved in 82% cases, being tigecycline a potentially good option in the empiric treatment of very severe infections.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Cohort Studies; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae Infections; Female; Humans; Intraabdominal Infections; Male; Middle Aged; Minocycline; Postoperative Complications; Prospective Studies; Risk Factors; Spain; Tigecycline

As part of the multicentre Antibiotic Therapy Optimisation Study, MIC values of 19 non-β-lactam agents were determined for third-generation cephalosporin-resistant Escherichia coli , Klebsiella species and Enterobacter species (3GCREB) isolates collected in German hospitals.. A total of 328 E. coli , 35 Klebsiella spp. (1 Klebsiella oxytoca and 34 Klebsiella pneumoniae ) and 16 Enterobacter spp. (1 Enterobacter aerogenes and 15 Enterobacter cloacae ) isolates were submitted to broth microdilution antimicrobial susceptibility testing with the MICRONAUT system. MICs of fluoroquinolones (levofloxacin and moxifloxacin), aminoglycosides (gentamicin, tobramycin, amikacin, streptomycin, neomycin and paromomycin), tetracyclines (tetracycline, minocycline and tigecycline), macrolides (erythromycin, clarithromycin and azithromycin) and miscellaneous agents [trimethoprim/sulfamethoxazole, chloramphenicol, nitrofurantoin, colistin and fosfomycin intravenous (iv)] were determined and reviewed against 2016 EUCAST breakpoints.. The MIC of levofloxacin was >2 mg/L for 128 of 328 E. coli and 8 of 35 Klebsiella spp., but only 1 of 16 Enterobacter spp. Rates of resistance to trimethoprim/sulfamethoxazole were high (>70%), except for Enterobacter spp. Rates of resistance to colistin and fosfomycin iv were still low. About 20% of the tested isolates were resistant to chloramphenicol. Only 1 (of 328) E. coli isolate had an MIC of amikacin >16 mg/L and only 33 of 328 E. coli and 1 of 35 Klebsiella spp. had an MIC of tobramycin >4 mg/L, whereas average gentamicin MICs were in general more elevated. A tigecycline MIC >2 mg/L was only found for 1 of 16 Enterobacter spp., but in none of the E. coli or Klebsiella spp. isolates.. Our study gives insight into previously unreported non-β-lactam MIC distributions of 3GCREB isolates.

Topics: Anti-Bacterial Agents; beta-Lactamases; beta-Lactams; Cephalosporin Resistance; Cephalosporins; Colistin; Drug Resistance, Bacterial; Enterobacter; Enterobacteriaceae Infections; Escherichia coli; Hospitalization; Humans; Klebsiella; Microbial Sensitivity Tests; Minocycline; Tertiary Care Centers; Tetracycline; Tigecycline

Carbapenems resistance in Enterobacter spp. has increased in the last decade, few studies, however, described the mechanisms of resistance in this bacterium. This study evaluated clonality and mechanisms of carbapenems resistance in clinical isolates of Enterobacter spp. identified in three hospitals in Brazil (Hospital A, B and C) over 7-year.. Antibiotics sensitivity, pulsed-field gel electrophoresis (PFGE), PCR for carbapenemase and efflux pump genes were performed for all carbapenems-resistant isolates. Outer-membrane protein (OMP) was evaluated based on PFGE profile.. A total of 130 isolates of Enterobacter spp were analyzed, 44/105 (41, 9%) E. aerogenes and 8/25 (32,0%) E. cloacae were resistant to carbapenems. All isolates were susceptible to fosfomycin, polymyxin B and tigecycline. KPC was present in 88.6% of E. aerogenes and in all E. cloacae resistant to carbapenems. The carbapenems-resistant E. aerogenes identified in hospital A belonged to six clones, however, a predominant clone was identified in this hospital over the study period. There is a predominant clone in Hospital B and Hospital C as well. The mechanisms of resistance to carbapenems differ among subtypes. Most of the isolates co-harbored blaKPC, blaTEM and /or blaCTX associated with decreased or lost of 35-36KDa and or 39 KDa OMP. The efflux pump AcrAB-TolC gene was only identified in carbapenems-resistant E. cloacae.. There was a predominant clone in each hospital suggesting that cross-transmission of carbapenems-resistant Enterobacter spp. was frequent. The isolates presented multiple mechanisms of resistance to carbapenems including OMP alteration.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Brazil; Carbapenems; DNA, Bacterial; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Enterobacter; Enterobacteriaceae Infections; Female; Fosfomycin; Genes, Bacterial; Hospitals; Humans; Male; Membrane Proteins; Microbial Sensitivity Tests; Middle Aged; Minocycline; Polymerase Chain Reaction; Polymyxin B; Tigecycline; Young Adult

Four NDM-1-producing Enterobacteriaceae strains (three Klebsiella pneumoniae and one Citrobacter koseri) were isolated between 2009 and 2011 through a nationwide surveillance for carbapenem-resistant Enterobacteriaceae in Croatia to study the molecular genetic background of blaNDM and the responsible plasmid types. Phenotypically, the clinical strains proved to be multidrug resistant. All strains remained susceptible to tigecycline and colistin. The clinical strains harbored variable antibiotic resistance determinants, notably, blaNDM-1, blaTEM-1, blaSHV-1, blaSHV-12, blaOXA-1, blaOXA-9, blaCTX-M-15, blaCMY-4, qnrB1, and aac(6')Ib-cr in different combinations. Two K. pneumoniae belonged to sequence type ST15 and one strain to ST16. As for the plasmid types, C. koseri and one of the ST15 K. pneumoniae carried IncR, and the second ST15 K. pneumoniae carried IncR and colE. The K. pneumoniae ST16 strain hosted A/C and colE plasmids. The blaNDM-1 gene was detected on conjugative high-molecular-weight plasmids, namely, A/C and IncR types. It is noteworthy that this is the first description of K. pneumoniae ST16 expressing NDM-1 in Europe. Remarkably, our study underscores the importance of the IncR plasmid as a reservoir of multidrug resistance. To the best of our knowledge, the IncR plasmid carrying blaNDM-1 in C. koseri is reported for the first time.

Topics: Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Citrobacter koseri; Colistin; Conjugation, Genetic; Croatia; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae Infections; Gene Expression; Gene Transfer, Horizontal; Humans; Isoenzymes; Klebsiella pneumoniae; Microbial Sensitivity Tests; Minocycline; Plasmids; Sequence Analysis, DNA; 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

The widespread multidrug-resistant Enterobacteriaceae pose a serious therapeutic challenge. Colistin and tigecycline are potential antimicrobial agents for treating infections caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. We evaluated the in-vitro activity of colistin sulfate against 253 ESBL producers isolated from patients admitted to a medical center in southern Taiwan (Escherichia coli, n = 82; Klebsiella pneumoniae, n = 102; Enterobacter cloacae, n = 34; and Serratia marcescens, n = 35). Colistin showed promising in-vitro activity against E. coli, K. pneumoniae, and E. cloacae, but not S. marcescens. One ESBL-producing K. pneumoniae strain with resistance to carbapenems (ertapenem, imipenem, and meropenem) was selected for time-killing studies. A combination of colistin and tigecycline showed synergism, but there was an inoculum effect. In conclusion, colistin was active against most ESBL-producing Enterobacteriaceae, and a combination of colistin with tigecycline was synergistic against some highly resistant strains, even those with carbapenem resistance.

Topics: Anti-Bacterial Agents; beta-Lactamases; Colistin; Enterobacter cloacae; Enterobacteriaceae Infections; Escherichia coli; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests; Minocycline; Serratia marcescens; Tigecycline

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Enterobacteriaceae; Enterobacteriaceae Infections; Fosfomycin; Genotype; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

We evaluated the in vitro activity of tigecycline and selected comparator agents tested against carbapenem-resistant Enterobacteriaceae (CRE) isolated from European medical centers. A total of 14,286 clinically significant nonduplicate Enterobacteriaceae isolates were collected from 18 European countries in 2010-2013. Susceptibility testing was performed by CLSI broth microdilution method, and isolates with a meropenem or imipenem MIC at ≥4μg/mL were categorized as CRE. Selected CRE strains were screened for acquired carbapenemases by multiplex polymerase chain reaction and sequencing. Overall, 2.0% (280/14,286) of Enterobacteriaceae strains were CRE. The highest CRE occurrence was observed in Poland (17.3%; 70/405), followed by Italy (7.5%, 130/1,743), Greece (7.4%; 45/605), and Romania (5.0%; 8/157). The most common CRE species were Klebsiella pneumoniae (242; 86.4%) and Enterobacter cloacae (22; 7.9%), and the most common carbapenemases were KPC-2/3 (85.4%) and VIM-type (12.5%). Only tigecycline (88.6% susceptible) and colistin (73.9%) exhibited good in vitro activity (>70.0%) against CRE strains.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Carbapenems; Enterobacteriaceae; Enterobacteriaceae Infections; Epidemiological Monitoring; Europe; Humans; Microbial Sensitivity Tests; Minocycline; Multiplex Polymerase Chain Reaction; Sequence Analysis, DNA; Tigecycline

Carbapenemase-producing Enterobacteriaceae (CPE) cause serious infections and are associated with high mortality in part due to limited treatment options. The in vitro activities of the new aminoglycoside plazomicin and comparators were evaluated against a collection of 164 CPE (VIM-1, n=125; KPC-2, n=34; OXA-48, n=4; and IMP-22, n=1). MIC90 values of gentamicin, tobramycin and amikacin were 256, 64 and 16 mg/L, respectively. Plazomicin exhibited an MIC range of 0.12-4 mg/L with MIC50 and MIC90 values of 0.25 and 1 mg/L. The MICs of plazomicin did not correlate with the other aminoglycoside MICs, with the resistance phenotype or with the carbapenemase harboured. Chequerboard experiments against 10 carbapenemase-producing Klebsiella pneumoniae isolates showed that combinations of plazomicin with colistin yielded synergy against 60% of the strains. Synergy of plazomicin with meropenem or fosfomycin was detected against 20% and 25% of the isolates, respectively. Using time-kill methodology, the interactions of plazomicin at 2×, 1× and 0.5× MIC with meropenem, colistin, fosfomycin or tigecycline at steady-state concentrations against two K. pneumoniae carrying the VIM-1 enzyme were investigated. Bactericidal activity was evident for both isolates at 2× MIC of plazomicin. Synergy was observed when plazomicin was combined with meropenem, colistin or fosfomycin against both isolates, whilst the combination with tigecycline resulted in indifference. Antagonism was not observed for any of the combinations tested. The results of this study suggest that plazomicin may address the need for new therapeutic options for the treatment of infections due to CPE.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Enterobacter; Enterobacteriaceae Infections; Fosfomycin; Humans; Klebsiella oxytoca; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Minocycline; Serratia marcescens; Sisomicin; Thienamycins; Tigecycline

Escherichia coli (328 isolates), Klebsiella pneumoniae (296), Klebsiella oxytoca (44), and Proteus mirabilis (33) isolates collected during 2012 from the nine U.S. census regions and displaying extended-spectrum-β-lactamase (ESBL) phenotypes were evaluated for the presence of β-lactamase genes, and antimicrobial susceptibility profiles were analyzed. The highest ESBL rates were noted for K. pneumoniae (16.0%, versus 4.8 to 11.9% for the other species) and in the Mid-Atlantic and West South Central census regions. CTX-M group 1 (including CTX-M-15) was detected in 303 strains and was widespread throughout the United States but was more prevalent in the West South Central, Mid-Atlantic, and East North Central regions. KPC producers (118 strains [112 K. pneumoniae strains]) were detected in all regions and were most frequent in the Mid-Atlantic region (58 strains). Thirteen KPC producers also carried blaCTX-M. SHV genes encoding ESBL activity were detected among 176 isolates. Other β-lactamase genes observed were CTX-M group 9 (72 isolates), FOX (10), TEM ESBL (9), DHA (7), CTX-M group 2 (3), NDM-1 (2 [Colorado]), and CTX-M groups 8 and 25 (1). Additionally, 62.9% of isolates carried ≥2 β-lactamase genes. KPC producers were highly resistant to multiple agents, but ceftazidime-avibactam (MIC50/90, 0.5/2 μg/ml) and tigecycline (MIC50/90, 0.5/1 μg/ml) were the most active agents tested. Overall, meropenem (MIC50, ≤0.06 μg/ml), ceftazidime-avibactam (MIC50, 0.12 to 0.5 μg/ml), and tigecycline (MIC50, 0.12 to 2 μg/ml) were the most active antimicrobials when tested against this collection. NDM-1 producers were resistant to all β-lactams tested. The diversity and increasing prevalence of β-lactamase-producing Enterobacteriaceae have been documented, and ceftazidime-avibactam was very active against the vast majority of β-lactamase-producing strains isolated from U.S. hospitals.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Ceftazidime; Enterobacteriaceae Infections; Escherichia coli; Gene Expression; Genetic Variation; Humans; Klebsiella oxytoca; Klebsiella pneumoniae; Microbial Sensitivity Tests; Minocycline; Monobactams; Plasmids; Proteus mirabilis; Tigecycline; United States

Five carbapenem-resistant strains (three Klebsiella pneumoniae, one Escherichia coli, and one Enterobacter aerogenes) were isolated between 2009 and 2012 at the Verona University Hospital, Italy, during an epidemiological analysis of antibiotic resistance determinants and plasmid profiles in Enterobacteriaceae. Two out of the five strains, K. pneumoniae E530 and E. coli E558, were cultured from bile and abdominal drainage, respectively, of a single patient. The strains were resistant to beta-lactams and fluoroquinolones, and susceptible to tigecycline and colistin. All the strains harboured bla(KPC-3), bla(TEM-1), and bla(OXA-9), and the three K. pneumoniae additionally carried blaSHV-11 and aac(6')Ib. The bla(KPC-3) was inserted in transposon Tn4401a. All the strains hosted an FIIk-type plasmid, and the three K. pneumoniae coharboured an colE-type plasmid. Transconjugants, besides bla(KPC-3), harboured bla(TEM-1) and bla(OXA-9) genes on FIIk-type plasmid. K. pneumoniae E301 was ST258, while strain E530 and C525 belonged to the ST512, and E. coli E558 was ST43. To our best knowledge, this is the first report that strongly supports the transmission of bla(KPC-3) from ST512 K. pneumoniae to E. coli ST43 in a single patient, a phenomenon of both clinical and microbiological importance.

Topics: Abdominal Abscess; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; beta-Lactams; Bile; Colistin; Conjugation, Genetic; DNA Transposable Elements; Drug Resistance, Multiple, Bacterial; Enterobacter aerogenes; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Infections; Fluoroquinolones; Gene Expression; Humans; Klebsiella Infections; Klebsiella pneumoniae; Minocycline; Plasmids; Tigecycline

We assessed the activity of tigecycline (TGC) combined with colistin (COL) against carbapenem-resistant enterobacteria. Synergy occurred in vitro against the majority of isolates, with the exception of Serratia marcescens. In a simple animal model (Galleria mellonella), TGC-COL was superior (P < 0.01) in treating Escherichia coli, Klebsiella pneumoniae, and Enterobacter infections, including those with TGC-COL resistance. Clinical studies are needed to determine whether TGC-COL regimens may be a viable option.

Topics: Animals; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Colistin; Disease Models, Animal; Drug Resistance, Bacterial; Drug Therapy, Combination; Enterobacter; Enterobacteriaceae; Enterobacteriaceae Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Minocycline; Moths; Tigecycline

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

We report the second pediatric case of New Delhi metallo-β-lactamase-1-producing Enterobacteriaceae in the United States. Laboratory methods included various phenotypic antimicrobial susceptibility testing assays, as well as polymerase chain reaction assays for carbapenemase-encoding genes. Laboratory challenges and the limited number of effective antimicrobial agents and the lack of pediatric-specific safety and efficacy data for these drugs are discussed.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Child; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Fosfomycin; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline; United States

The prevalence of carbapenemase-producing Enterobacteriaceae (CPE) has increased during the past 10 years. Its detection is frequently difficult, because they do not always show a minimum inhibitory concentration (MIC) value for carbapenems in the resistance range. Both broth microdilution and agar dilution methods are more sensitive than disk diffusion method, Etest and automated systems. Studies on antimicrobial treatment are based on a limited number of patients; therefore, the optimal treatment is not well established. Combination therapy with two active drugs appears to be more effective than monotherapy. Combination of a carbapenem with another active agent--preferentially an aminoglycoside or colistin--could lower mortality provided that the MIC is ≤4 mg/l and probably ≤8 mg/l, and is administered in a higher-dose/prolonged-infusion regimen. An aggressive infection control and prevention strategy is recommended, including reinforcement of hand hygiene, using contact precautions and early detection of CPE through use of targeted surveillance.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Drug Resistance, Multiple; Drug Therapy, Combination; Enterobacteriaceae; Enterobacteriaceae Infections; Fosfomycin; Humans; Infection Control; Microbial Sensitivity Tests; Minocycline; Molecular Typing; Polymyxins; Practice Guidelines as Topic; Tigecycline

Limited antimicrobials remain active for treating severe infections due to KPC-producing pathogens, and optimal regimens have not been established. In murine thigh infections caused by nine KPC-producing clinical strains of Enterobacteriaceae (meropenem MICs, 1 to 4 μg/ml), we evaluated the activities of tigecycline, colistin, meropenem, rifampin, and gentamicin in single and combination regimens lasting for 24 h and 48 h. Rifampin, tigecycline, and gentamicin were the most effective monotherapies, reducing significantly the CFU counts yielded from thighs infected by 88.9 to 100%, 77.8 to 88.9%, and 66.7 to 88.9% of strains, respectively; meropenem and colistin alone exhibited considerably lower performance (significant CFU reduction in 33.3% and 22.2 to 33.3% of the strains, respectively). The addition of rifampin or gentamicin to tigecycline produced synergistic effect in most strains, while antagonism was observed in 33.3 to 44.4% of the strains when colistin was added to tigecycline and in 44.4 to 55.5% of the strains for meropenem combination with tigecycline. Tigecycline combinations with gentamicin or with rifampin caused higher CFU reductions than did tigecycline plus colistin or plus meropenem with almost all strains. Furthermore, tigecycline plus gentamicin was significantly more effective than tigecycline plus colistin or tigecycline plus meropenem in 33.3 to 44.4% and 55.5 to 66.7% of the strains, respectively, while tigecycline plus rifampin significantly outperformed tigecycline plus colistin and tigecycline plus meropenem in 33.3% and 66.7 to 77.8% of the strains, respectively. Overall, our in vivo study showed that tigecycline plus rifampin or plus gentamicin is a robust regimen against soft tissue infections caused by KPC-producing strains. The combinations of tigecycline with colistin or meropenem should be considered with caution in clinical practice.

Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Colony Count, Microbial; Drug Synergism; Drug Therapy, Combination; Enterobacteriaceae Infections; Escherichia coli; Female; Gentamicins; Klebsiella pneumoniae; Meropenem; Mice; Microbial Sensitivity Tests; Minocycline; Rifampin; Thienamycins; Thigh; Tigecycline

Progressively enhanced activity of a humanized tigecycline (TGC) regimen was noted over 3 days against an extended-spectrum-β-lactamase (ESBL)-producing Escherichia coli isolate and an ESBL-producing Klebsiella pneumoniae isolate. Bacterial density reduction approximated 3 log(10) approaching bactericidal activity at 72 h. This level of activity has not been previously noted for compounds such as tetracyclines, normally considered bacteriostatic antimicrobials. Extended regimen studies in vivo may aid in better delineation of antimicrobial effects, producing improved correlation with clinical outcomes.

Topics: Animals; Anti-Bacterial Agents; Area Under Curve; beta-Lactamases; Colony Count, Microbial; Enterobacteriaceae Infections; Escherichia coli; Gene Expression; Klebsiella pneumoniae; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Minocycline; Thigh; Tigecycline; Time Factors

Topics: Aged; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Cross Infection; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Male; Minocycline; Molecular Sequence Data; Tigecycline

The intrinsically encoded ramA gene has been linked to tigecycline resistance through the up-regulation of efflux pump AcrAB in Enterobacter cloacae. The molecular basis for increased ramA expression in E. cloacae and Enterobacter aerogenes, as well as the role of AraC regulator rarA, has not yet been shown. To ascertain the intrinsic molecular mechanism(s) involved in tigecycline resistance in Enterobacter spp., we analysed the expression levels of ramA and rarA and corresponding efflux pump genes acrAB and oqxAB in Enterobacter spp. clinical isolates.. The expression levels of ramA, rarA, oqxA and acrA were tested by quantitative real-time RT-PCR. The ramR open reading frames of the ramA-overexpressing strains were sequenced; strains harbouring mutations were transformed with wild-type ramR to study altered ramA expression and tigecycline susceptibility.. Tigecycline resistance was mediated primarily by increased ramA expression in E. cloacae and E. aerogenes. Only the ramA-overexpressing E. cloacae isolates showed increased rarA and oqxA expression. Upon complementation with wild-type ramR, all Enterobacter spp. containing ramR mutations exhibited decreased ramA and acrA expression and increased tigecycline susceptibility. Exceptions were one E. cloacae strain and one E. aerogenes strain, where a decrease in ramA levels was not accompanied by lower acrA expression.. Increased ramA expression due to ramR deregulation is the primary mediator of tigecycline resistance in clinical isolates of E. cloacae and E. aerogenes. However, some ramA-overexpressing isolates do not show changes in ramR, suggesting alternate pathways of ramA regulation; the rarA regulator and the oqxAB efflux pump may also play a role in tigecycline resistance in E. cloacae.

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Enterobacter aerogenes; Enterobacter cloacae; Enterobacteriaceae Infections; Gene Expression Profiling; Gene Expression Regulation, Bacterial; Genes, Bacterial; Humans; Membrane Transport Proteins; Minocycline; Real-Time Polymerase Chain Reaction; Sequence Analysis, DNA; Tigecycline; Transcription Factors

New Delhi metallo-β-lactamase-1 (NDM-1)-producing Enterobacteriaceae have emerged as a global threat. The aim of this study was to assess the efficacies of colistin and tigecycline in an experimental model of pneumonia caused by NDM-1-producing Escherichia coli and Klebsiella pneumoniae. The susceptibilities of K. pneumoniae NDM, E. coli NDM and K. pneumoniae ATCC 29665 were determined using the broth microdilution technique. The pharmacokinetics of colistin and tigecycline in an experimental model of pneumonia were performed using immunocompetent C57BL/6 mice. Mice were treated with colistin (60 mg/kg/day) or tigecycline (10 mg/kg/day). Mortality, bacteraemia and lung bacterial concentrations were recorded. The strains were susceptible to colistin and tigecycline. The ratio of area under the concentration-time curve/minimum inhibitory concentration (AUC/MIC) for colistin was 158.5 (all three strains) and that for tigecycline was 18.5 (K. pneumoniae NDM) and 37 (K. pneumoniae ATCC 29665 and E. coli NDM). In vivo, colistin decreased bacterial lung concentrations of K. pneumoniae NDM and K. pneumoniae ATCC 29665 by 1.16 log colony-forming units (CFU)/g and 2.23 logCFU/g, respectively, compared with controls (not significant). Tigecycline reduced K. pneumoniae NDM and K. pneumoniae ATCC 29665 load by 2.67 logCFU/g and 4.62 logCFU/g (P<0.05). Colistin and tigecycline decreased lung concentrations of E. coli NDM by 2.27 logCFU/g and 4.15 logCFU/g (P<0.05), respectively, compared with controls, and was more active than colistin (P<0.05). In conclusion, these results suggest that colistin is inappropriate for treating pneumonia due to NDM-1-producing K. pneumoniae and its efficacy was suboptimal against NDM-1-producing E. coli. A high tigecycline dose was efficacious for treating experimental pneumonia due to NDM-1-producing E. coli and K. pneumoniae.

Topics: Animals; Anti-Bacterial Agents; Bacteremia; Bacterial Load; Bacterial Proteins; beta-Lactamases; Colistin; Disease Models, Animal; Drug Evaluation, Preclinical; Enterobacteriaceae Infections; Escherichia coli; Female; Klebsiella pneumoniae; Lung; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Minocycline; Tigecycline

Topics: Anti-Bacterial Agents; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Intraabdominal Infections; Microbial Sensitivity Tests; Minocycline; Tigecycline

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

To assess the susceptibility trends of community-acquired extended-spectrum β-Iactamase (ESBL)-producing urinary isolates with particular reference to fosfomycin, nitrofurantoin and tigecycline.. Seven hospitals across the United Arab Emirates participated in this study from June 2008 to March 2010. The antibiotic sensitivity of ESBL-producing uropathogens to a panel of antibiotics including tigecycline, fosfomycin and nitrofurantoin was assessed. The Hyplex ESBL identification system (h-ES-ID) was used for genotypic identification.. Two hundred and ninety-two ESBL-producing Enterobacteriaceae isolates were identified during the study period. Of these, 182 (62%) were urinary isolates and comprised of Escherichia coli: 149 (81.9%), Klebsiella pneumoniae: 30 (16.5%) and Proteus mirabilis: 3 (1.6%). Of the 182 urinary isolates, 179 (98.3%) were from patients with community onset urinary tract infections. The h-ES-ID system identified 172 (94.5%) of the urinary isolates as CTX-M positive. All isolates were susceptible to imipenem and meropenem. Over half of the isolates showed resistance to gentamicin (98; 53.8%), trimethoprim-sulfamethoxazole (139; 76.4%) and ciprofloxacin (143; 78.6%). Sensitivity to nitrofurantoin and fosfomycin was 90 and 100%, respectively. Two CTX-M-positive K. pneumoniae isolates with tigecycline resistance (MIC >4 µg/ml) were identified.. There is dissemination of CTX-M ESBL-producing urinary pathogens into the community. Fosfomycin and nitrofurantoin were active against ESBL-positive uropathogens, and emergence of tigecycline resistance needs close monitoring.

Topics: Anti-Bacterial Agents; Anti-Infective Agents, Urinary; beta-Lactam Resistance; Chi-Square Distribution; Enterobacteriaceae; Enterobacteriaceae Infections; Fosfomycin; Genotype; Humans; Minocycline; Nitrofurantoin; Tigecycline; United Arab Emirates; Urinary Tract Infections

From June to September 2011, a total of 305 ertapenem-nonsusceptible Enterobacteriaceae isolates (MICs of ertapenem ≥ 1 μg/ml) were collected from 11 hospitals in different parts of Taiwan. The MICs of 12 antimicrobial agents against these isolates were determined using the broth microdilution method, and genes for carbapenemases were detected using PCR. Genotypes of isolates possessing carbapenemase genes were identified by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing. The ertapenem-nonsusceptible Enterobacteriaceae isolates included Klebsiella pneumoniae (n = 219), Escherichia coli (n = 64), Enterobacter cloacae (n = 15), and other species (n = 7). Seven (2.3%) of the ertapenem-nonsusceptible Enterobacteriaceae isolates exhibited colistin MICs of >4 μg/ml, and 24 (7.9%) were not susceptible to tigecycline (MICs > 2 μg/ml). A total of 29 (9.5%) isolates carried genes encoding carbapenemases, namely, K. pneumoniae carbapenemase-2 (KPC-2) in 16 (7.3%) isolates of K. pneumoniae (KPC-2-KP) and IMP-8 in 5 (2.3%) isolates of K. pneumoniae, 5 (33.3%) isolates of E. cloacae, 1 isolate of E. coli, 1 isolate of Klebsiella oxytoca, and one isolate of Citrobacter freundii. The 16 KPC-2-KP isolates were isolated from patients at four different hospitals in northern Taiwan. All 16 of the KPC-2-KP isolates were susceptible to amikacin and colistin and had a similar pulsotype (pulsotype 1) and the same sequence type (sequence type 11). Infections due to KPC-2-KP mainly occurred in severely ill patients in the intensive care unit (n = 14, 88%). Four patients with infections due to KPC-2-KP died within 14 days of hospitalization. The findings are the first to demonstrate intrahospital and interhospital dissemination of KPC-2-KP in northern Taiwan.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Citrobacter freundii; Electrophoresis, Gel, Pulsed-Field; Enterobacter cloacae; Enterobacteriaceae; Enterobacteriaceae Infections; Genotype; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests; Minocycline; Polymerase Chain Reaction; Tigecycline

From 2005 to 2009, at Detroit Medical Center, the prevalence of Providencia stuartii increased from 0.52 to 0.91/1000 patient-days (p<0.001). The use of colistin also increased (p<0.001) during the study period. The increase in the prevalence of P. stuartii was associated with an increased use of colistin (p<0.001). Facilities that frequently use colistin and tigecycline should closely monitor the prevalence of P. stuartii along with other Proteeae, since these organisms are intrinsically resistant to colistin and tigecycline.

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae Infections; Female; Humans; Logistic Models; Michigan; Middle Aged; Minocycline; Prevalence; Providencia; Retrospective Studies; Tertiary Care Centers; Tigecycline

Extended-spectrum β-lactamase (ESBL)-producing organisms are spreading worldwide in hospital and community settings.. A total of 328 unduplicated ESBL-producing Enterobacteriaceae isolated in 2008 and 2009 at the University Hospital of Tübingen were analysed retrospectively.. Escherichia coli (n = 253) and Klebsiella spp. (n = 46) were the most frequent ESBL-producing species. The ESBL rates among E. coli and Klebsiella spp. increased from 3.8 and 2.1%, respectively, in 2008, to 5.2 and 2.4%, respectively, in 2009. Two E. coli and 3 Klebsiella pneumoniae ESBL producers were non-susceptible to ertapenem, most likely due to loss of porins. Antimicrobial susceptibility testing of selected, molecularly characterized ESBL producers revealed susceptibility to tigecycline among 97.9% (191/195) of the E. coli and 78.8% (26/33) of the K. pneumoniae isolates. PCR analysis and sequencing showed the presence of CTX-M-type enzymes in 91.3% of the E. coli and 87.9% of the K. pneumoniae isolates, whereby bla(CTX-M-15) was the most frequent ESBL gene both in E. coli (50.0%) and K. pneumoniae (51.5%). Only 7 single cases of potential patient-to-patient transmissions of E. coli strains were observed.. Our data suggest that the increase in ESBL-producing E. coli and K. pneumoniae isolates at our hospital is mainly caused by growing import of Enterobacteriaceae harbouring CTX-M-type ESBLs.

Topics: beta-Lactamases; beta-Lactams; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae Infections; Ertapenem; Escherichia coli; Germany; Hospitals, University; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests; Minocycline; Prevalence; Retrospective Studies; Tigecycline

To assess the in vitro susceptibility of multidrug-resistant Enterobacteriaceae (MDRE) isolates to tigecycline.. Clinical isolates of MDRE tested in this study were obtained from 91 hospitals in Belgium during the period January 2010 to April 2010. MICs of tigecycline were determined by Vitek 2 (VTK) and by the reference broth microdilution (BMD) method, and the results were interpreted based on the 2011 MIC interpretative criteria recommended by EUCAST.. A total of 501 non-duplicate MDRE isolates were tested. These comprised 284 isolates of Escherichia coli [255 (89.7%) were extended-spectrum β-lactamase (ESBL)-producing isolates], 72 isolates of Klebsiella pneumoniae [53 (73.6%) were ESBL-producing isolates], 72 isolates of Enterobacter aerogenes, 33 isolates of Enterobacter cloacae, 19 isolates of Klebsiella oxytoca and 21 miscellaneous others. The MIC(90) values of tigecycline for E. coli and non-E. coli ESBL-producing Enterobacteriaceae isolates were 0.5 and 2 mg/L by BMD, and 0.5 and 8 mg/L by VTK, respectively. The highest essential and categorical agreement rates between VTK and BMD results using EUCAST breakpoints were observed in E. coli isolates (97.2%), while lower and unacceptable essential and categorical agreement rates were obtained for isolates belonging to species other than E. coli (81.1% and 59.4%, respectively).. VTK appears to be a suitable method for routine susceptibility testing of tigecycline only for E. coli isolates, while BMD should be preferred for other Enterobacteriaceae species isolates.

Topics: Anti-Bacterial Agents; Belgium; Drug Resistance, Multiple, Bacterial; Enterobacter; Enterobacteriaceae Infections; Escherichia coli; Hospitals; Humans; Klebsiella; Microbial Sensitivity Tests; Minocycline; Tigecycline

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: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Minocycline

Antibiotic combinations including tigecycline have not been studied against Klebsiella pneumoniae carbapenemase (KPC)-producing pathogens. Tigecycline alone and combined with colistin and meropenem was tested against eight genetically unrelated KPC-producing clinical strains of Enterobacteriaceae (four K. pneumoniae, two Escherichia coli, one Enterobacter cloacae and one Serratia marcescens) by time-kill assay. Tigecycline displayed a concentration-independent bacteriostatic activity in seven strains and bactericidal activity in one strain. Colistin showed bactericidal activity at 4× the minimum inhibitory concentration (MIC) in three strains and was bacteriostatic for the remaining strains and concentrations. Meropenem was bactericidal in three strains and bacteriostatic in five strains. The tigecycline+meropenem combination was not bactericidal against the four K. pneumoniae strains and was non-synergistic against all eight strains. Tigecycline+colistin was bactericidal against all strains at most time intervals and concentrations and was also synergistic at 1× and 2× MIC against most strains up to 4-8h and at 4× MIC up to 24 h against all strains. These findings suggest that, at most drug concentrations, tigecycline, colistin and meropenem as single agents do not exhibit efficient bactericidal activity against most of the KPC-producing strains. Tigecycline alone might be a therapeutic option for infections caused by KPC-producers when bacteriostatic activity is adequate or combined with colistin when bactericidal activity is necessary. Additional in vivo tests are warranted to assess better the killing kinetics of tigecycline combinations against KPC-producers.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Combinations; Drug Resistance, Bacterial; Enterobacter cloacae; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Humans; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Minocycline; Serratia marcescens; Thienamycins; Tigecycline

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactams; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Ertapenem; Fosfomycin; Humans; Microbial Sensitivity Tests; Minocycline; Quinolones; Tigecycline

Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and methicillin resistant Staphylococcus aureus (MRSA) are important nosocomial pathogens. This study reports the in vitro activity of tigecycline against 573 and 482 ESBL-producing Enterobacteriaceae and MRSA isolates, respectively. More than 94% of all tested isolates were susceptible to tigecycline; MIC(90) found was 0.25 to 2 mg/L for ESBL-producing Enterobacteriaceae and was 0.125 mg/L for MRSA. Tigecycline demonstrated excellent in vitro activity against a wide spectrum of nosocomial pathogens.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamases; Cross Infection; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Mexico; Microbial Sensitivity Tests; Middle Aged; Minocycline; Staphylococcal Infections; Tigecycline; Young Adult

Antimicrobial resistance among Gram-negatives is increasing; treatment options are limited. Although tigecycline is used infrequently for urinary tract infection (UTI), greater use is likely as resistance increases. We report successful treatment of an episode of febrile UTI and probable prostatitis with tigecycline, and summarize the relevant literature.

Topics: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Enterobacter; Enterobacteriaceae Infections; Humans; Male; Middle Aged; Minocycline; Prostatitis; Tigecycline; Treatment Outcome; Urinary Tract Infections

Topics: Anti-Bacterial Agents; Enterobacteriaceae Infections; Humans; Male; Minocycline; Prostatitis; Tigecycline; Urinary Tract Infections

We investigated the prevalence of metallo-β-lactamases (MBLs) among 1,827 Enterobacteriaceae isolates collected in 2006 and evaluated the VITEK 2 microbiology system, modified Hodge test, and 2 combined disk tests as the screening tools for MBLs by using these isolates and 77 previously characterized IMP-8 producers. The IMP-8 MBL was identified in 18 isolates of 2006, and the IMP-8-positive isolates represented 0.2%, 1.1%, and 5.0% of all Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae isolates, respectively. Only one-third of all MBL producers could be recognized by either VITEK 2 or the Hodge test. MBL production could be identified in 38 (40%) of the 95 IMP-8-producing isolates by the combined disk test using meropenem disks supplemented by phenylboronic acid and EDTA, and only 2 (2.1%) isolates gave positive results in the combined disk test using meropenem disks supplemented with dipicolinic acid. Of all IMP-8 producers, 37.9%, 50.5%, and 32.6% were nonsusceptible to tigecycline, fluoroquinolones, and both, respectively. In conclusion, this study demonstrated the lack of distinct phenotypes that could be easily identified among the IMP-8-producing Enterobacteriaceae isolates at a Taiwanese hospital. Continuous surveillance and monitoring are needed because the widespread of tigecycline- and fluoroquinolone-coresistant MBL producers may become a serious therapeutic problem.

Topics: Anti-Bacterial Agents; beta-Lactamases; DNA, Bacterial; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Microbial Sensitivity Tests; Minocycline; Phenotype; Polymerase Chain Reaction; Taiwan; Tigecycline

Carbapenem-resistant Enterobacteriaceae (CRE) are rapidly emerging in hospitals in the United States and are posing a significant threat. To better understand the transmission dynamics and the acquisition of resistant strains, a thorough analysis of epidemiologic and molecular characteristics was performed.. CRE isolated at Detroit Medical Center were analyzed from September 2008 to September 2009. bla(KPC) genes were investigated by polymerase chain reaction (PCR), and repetitive extragenic palindromic PCR (rep-PCR) was used to determine genetic similarity among strains. Epidemiologic and outcomes analyses were performed.. Ninety-two unique patient CRE isolates were recovered. Sixty-eight strains (74%) were Klebsiella pneumoniae, 7 were Klebsiella oxytoca, 15 were Enterobacter species, and 2 were Escherichia coli. Fifteen isolates (16%) were resistant to colistin, 14 (16%) were resistant to tigecycline, and 2 were resistant to all antimicrobials tested. The mean ± standard deviation age of patients was 63 ± 2 years. Sixty patients (68%) were admitted to the hospital from long-term care facilities. Only 70% of patients received effective antimicrobial therapy when infection was suspected, with a mean time to appropriate therapy of 120 ± 23 hours following sample culturing. The mean length of hospitalization after sample culturing was 18.6 ± 2.5 days. Of 57 inpatients, 18 (32%) died in the hospital. Independent predictors for mortality were intensive care unit stay (odds ratio [OR], 15.8; P = .003) and co-colonization with CRE and either Acinetobacter baumannii or Pseudomonas aeruginosa (OR, 17.2; P = .006). Among K. pneumoniae CRE, rep-PCR revealed 2 genetically related strains that comprised 70% and 20% of isolates, respectively.. In this large U.S. cohort of patients with CRE infection, which reflects the modern continuum of medical care, co-colonization with CRE and A. baumannii or P. aeruginosa was associated with increased mortality. Two predominant clones of K. pneumoniae accounted for the majority of cases of CRE infection.

Topics: Academic Medical Centers; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenems; Child; Child, Preschool; Colistin; Disease Reservoirs; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Genotype; Hospital Mortality; Humans; Infant; Length of Stay; Male; Michigan; Middle Aged; Minocycline; Nursing Homes; Retrospective Studies; Tigecycline; Treatment Outcome; Young Adult

Carbapenem resistance in members of the Enterobacteriaceae is increasing. To evaluate the effects of tigecycline and polymyxin B against carbapenem-non-susceptible pathogens, 89 representative clinical carbapenem-non-susceptible Enterobacteriaceae isolates were recovered from seven hospitals from four cities in China during 2006-2009: 30 Serratia marcescens, 35 Klebsiella pneumoniae, seven Enterobacter cloacae, six Enterobacter aerogenes, five Escherichia coli, four Citrobacter freundii and two Klebsiella oxytoca isolates. Twenty-eight S. marcescens isolates were indistinguishable. The 35 K. pneumoniae isolates belonged to 12 clonal strains. Among the 89 Enterobacteriaceae isolates, 82 produced KPC-2, seven produced IMP (three produced KPC-2 simultaneously), three did not produce any carbapenemases and nine were deficient in porins. Polymyxin B was much more active than tigecycline against carbapenem-non-susceptible Enterobacteriaceae. The MIC(50) and MIC(90) of imipenem, meropenem, ertapenem, polymyxin B and tigecycline were 8 and 32 µg ml(-1), 8 and 32 µg ml(-1), 16 and 128 µg ml(-1), 0.5 and 16 µg ml(-1), and 4 and 16 µg ml(-1), respectively. Rates of susceptibility to imipenem, meropenem, ertapenem and polymyxin B were 30.0%, 27.5%, 2.5% and 89.2% by CLSI criteria. The rate of susceptibility to tigecycline was 40% and 17.5% by Food and Drug Administration (MIC ≤2 µg ml(-1)) and European Committee on Antimicrobial Susceptibility Testing (MIC ≤1 µg ml(-1)) criteria, respectively. KPC-2- or IMP-producing E. coli transconjugants exhibited reduced susceptibility to carbapenems but were susceptible to polymyxin B and tigecycline with an MIC range of 0.5-2 µg ml(-1), 0.25-2 µg ml(-1), 0.5-4 µg ml(-1), 0.5 µg ml(-1) and 0.5-1 µg ml(-1). In conclusion, carbapenem resistance in Enterobacteriaceae is mainly due to production of KPC-2, and polymyxin B is active for the carbapenem-resistant Enterobacteriaceae.

Topics: Anti-Bacterial Agents; Base Sequence; beta-Lactamases; Carbapenems; Conjugation, Genetic; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Microbial Sensitivity Tests; Minocycline; Polymyxin B; Sequence Analysis, DNA; Tigecycline

Tigecycline resistance remains rare amongst Enterobacteriaceae in the UK, as elsewhere, but has been associated with upregulation of the AcrAB efflux system. Using isolates of an Enterobacter cloacae strain that developed tigecycline resistance in vivo during ciprofloxacin therapy as well as laboratory-selected mutants, we investigated the role of this pump and the global regulator RamA in tigecycline resistance. Laboratory mutants were selected from a susceptible clinical isolate in vitro by exposure to increasing concentrations of tigecycline. Expression of the acrAB operon and the ramA gene was monitored by real-time reverse-transcription polymerase chain reaction (RT-PCR). Overexpression of ramA was achieved using the pBAD expression vector, whilst insertional inactivation of acrB with a gentamicin resistance cassette was achieved with the bacteriophage lambda Red recombination system. Increased tigecycline minimum inhibitory concentrations in the clinical isolate and a laboratory mutant were associated with increases in acrAB and ramA transcripts. Induction of increased ramA expression resulted in increased acrAB expression, whilst insertional inactivation of acrB restored full susceptibility to tigecycline. Treatment with ciprofloxacin, a substrate of AcrAB in E. cloacae, possibly selected for cross-resistance to tigecycline as a result of RamA-mediated AcrAB upregulation.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Bacterial Typing Techniques; Bacteriophage lambda; Ciprofloxacin; DNA Fingerprinting; DNA, Bacterial; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Enterobacter cloacae; Enterobacteriaceae Infections; Gene Expression Profiling; Humans; Male; Membrane Transport Proteins; Microbial Sensitivity Tests; Minocycline; Molecular Sequence Data; Mutagenesis, Insertional; Mutation; Reverse Transcriptase Polymerase Chain Reaction; Selection, Genetic; Sequence Analysis, DNA; Tigecycline; United Kingdom

Enterobacteriaceae clinical isolates harboring KPC-(178 strains) or CTX-M-encoding (67 strains) genes were collected during surveillance programs in the 2000-2007 period; and susceptibility was tested by broth microdilution methods. Organisms were dominantly collected in U.S. hospitals (93%). CTX-M-15 and -14 were the most prevalent CTX-M types (97%), all collected from the United States. KPC producers were isolated in the United States (160/178), Israel, China, and Argentina. bla(CTX-M)-carrying isolates were 95.5 and 98.5%, susceptible to Imipenem and meropenem respectively, and were all susceptible to tigecycline, whereas KPC-producing isolates were highly resistant to all antimicrobials tested except polymyxin B and tigecycline (90.6% and 99.4% susceptibility, respectively). The occurrence of KPC-producing and CTX-M-producing isolates has rapidly increased especially in U.S. hospitals, and expanded therapeutic options are needed to treat infections caused by these emerging organisms.

Topics: Anti-Bacterial Agents; Argentina; beta-Lactamases; China; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Genes, Bacterial; Hospitals; Humans; Imipenem; Israel; Meropenem; Microbial Sensitivity Tests; Minocycline; Polymyxin B; Thienamycins; Tigecycline; United States

Topics: Agar; Anti-Bacterial Agents; Culture Media; Drug Resistance, Bacterial; Enterobacter; Enterobacter aerogenes; Enterobacter cloacae; Enterobacteriaceae Infections; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Minocycline; Tigecycline

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

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

Bacterial resistance among Gram-negative pathogens is a challenging clinical problem. Tigecycline has been developed specifically to overcome resistance. The aim of this study was to assess the in vitro activity of tigecycline against ESBL-producing Escherichia coli, ESBL-producing Klebsiella spp., and multidrug-resistant Enterobacter spp. Between May 2007 and March 2008, 26 strains of ESBL-producing Escherichia coli, 10 strains of ESBL-producing Klebsiella spp., and 27 strains of multidrug-resistant Enterobacter spp. were isolated consecutively from inpatients with a documented infection in which the collected isolate was identified as the probable causative organism. The in vitro susceptibility against tigecycline was measured by the E-test method. MIC(50) values were 1 microg/ml, 2 microg/ml, and 3 microg/ml respectively. MIC(90) values were respectively 1.5 microg/ml, 4 microg/ml, and 12 microg/ml. Nonsusceptibility rates of 35%, 100%, and 96% respectively were found using EUCAST breakpoints. Despite the limited number of strains tested, our in vitro data suggest that tigecycline is unsuitable for the treatment of infections with multidrug-resistant Enterobacteriaceae in our setting. Therefore, we suggest that larger multicenter studies should be conducted to reconsider the value of tigecycline for the treatment of infections with multidrug-resistant, Gram-negative bacteria.

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

Potential tigecycline-Enterobacteriaceae susceptibility breakpoints were evaluated using 2 approaches, which differed in the nature of the probabilities assessed by MIC value. Using a previously derived tigecycline population pharmacokinetic model and Monte Carlo simulation, a probability density function of steady-state area under the concentration-time curve for 24 h (AUC(SS(0-24))) values for 9999 patients was generated. AUC(SS(0-24)) values were divided by clinically relevant fixed MIC values to derive AUC(SS(0-24))/MIC ratios, which were used to calculate the clinical response expectation by MIC value based upon a logistic regression model for efficacy (1st approach). For the 2nd approach, the probability of pharmacokinetic-pharmacodynamic (PK-PD) target attainment was calculated as the proportion of patients with AUC(SS(0-24))/MIC ratios greater than the threshold value of 6.96, the PK-PD target associated with optimal clinical response. Probabilities of clinical response and PK-PD target attainment were poorly correlated at MIC values >0.25 mg/L. For instance, the median probability of clinical success was 0.76, whereas the probability of PK-PD target attainment was 0.27 at an MIC value of 1 mg/L, suggesting that the probability of PK-PD target attainment metrics underestimates the clinical performance of tigecycline at higher MIC values.

Topics: Anti-Bacterial Agents; Area Under Curve; Bayes Theorem; Computer Simulation; Dose-Response Relationship, Drug; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Logistic Models; Male; Microbial Sensitivity Tests; Minocycline; Models, Biological; Monte Carlo Method; Skin Diseases, Bacterial; Tigecycline

Strains of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae have spread widely in Taiwan hospitals. In this study, we evaluated the in vitro antimicrobial activity of tigecycline against ESBL-producing Enterobacteriaceae, including Klebsiella pneumoniae, Serratia marcescens and Enterobacter cloacae.. 104 confirmed ESBL-producing bacteria were isolated from 4 hospitals in mid- and southern Taiwan between 2000 and 2006. The in vitro activity of tigecycline against these ESBL producers was tested by use of Etest strips.. The minimal tigecycline concentration at which 50% of isolates were inhibited and minimal concentration at which 90% of isolates were inhibited for ESBL-producing isolates ranged from 0.38 to 0.75 microg/mL and 0.5 to 1.5 microg/mL, respectively.. Tigecycline, a new semisynthetic glycylcycline, may be considered an alternative drug of choice for patients infected with ESBL-producing bacteria.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; beta-Lactams; Enterobacter cloacae; Enterobacteriaceae; Enterobacteriaceae Infections; Hospitals; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests; Minocycline; Serratia marcescens; Taiwan; 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

Tigecycline is a new broad-spectrum antibiotic. Nausea and vomiting are its most common side-effects. We describe here a case of severe acute pancreatitis related to tigecycline in order to highlight the possible occurrence of this adverse event and to remind clinicians to measure the lipase rate if in any doubt.

Topics: Acute Disease; Adult; Anti-Bacterial Agents; Enterobacter cloacae; Enterobacteriaceae Infections; Fosfomycin; Humans; Lipase; Male; Minocycline; Osteitis; Pancreatitis; Tigecycline

Tigecycline In-vitro Surveillance in Taiwan (TIST), initiated in 2006, is a nationwide surveillance programme designed to monitor longitudinally the in-vitro activity of tigecycline against commonly encountered resistant bacteria. This study compared the in-vitro activity of tigecycline against clinical isolates of resistant Gram-negative bacteria determined by the broth microdilution and Etest methods. A total of 622 isolates were collected from patients treated at 20 teaching hospitals. Tigecycline had excellent in-vitro activity against extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (N = 275) with MIC(90) 0.5 microg/mL and a 99.6% susceptibility rate, and also against ESBL-producing Klebsiella pneumoniae (N = 324) with MIC(90) 2 microg/mL and a 98.5% susceptibility rate. For ESBL-producing Proteus mirabilis (N = 15) the MIC(90) was 4 microg/mL with a 73.3% susceptibility rate. For ESBL-producing Klebsiella oxytoca (N = 8) the MIC(50) and MIC(90) were 0.5 and 1 microg/mL, respectively, with a 100% susceptibility rate. Limited agreement (<80%) was found between the broth microdilution and the Etest methods when determining the in-vitro activity of tigecycline against ESBL- producing K. pneumoniae and K. oxytoca.

Topics: Anti-Bacterial Agents; beta-Lactamases; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Microbial Sensitivity Tests; Minocycline; Taiwan; Tigecycline

Tigecycline activity was evaluated against 11808 pathogens isolated from 30 US medical centers. Susceptibility testing was performed by reference broth microdilution methods. Tigecycline (MIC(50/90), 0.12/0.25 microg/mL) was highly active against Staphylococcus aureus and coagulase-negative staphylococci, regardless of oxacillin resistance. This glycylcycline (MIC(50), 0.12 microg/mL) was 8- and 16-fold more potent than penicillin and linezolid against enterococci and was the most potent agent tested versus Streptococcus pneumoniae. Against Enterobacteriaceae, tigecycline (MIC(90), 1 microg/mL; 98.9% susceptible) was as active as imipenem. This study demonstrated the sustained potency of tigecycline against contemporary clinically relevant Gram-positive and Gram-negative pathogens; tigecycline resistance was rare (0.3%).

Topics: Anti-Bacterial Agents; Enterobacteriaceae; Enterobacteriaceae Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline; United States

A total of 104 carbapenemase (serine- and metallo-beta-lactamase [MbetaL])-producing strains of the Enterobacteriaceae family collected from 2000 to 2005 in medical centers distributed worldwide were tested against tigecycline and 25 comparators by reference broth microdilution methods. The most frequent carbapenemase was KPC-2 or -3 (73 strains), followed by VIM-1 (14), IMP-1 (11), SME-2 (5), and NMC-A (1). All serine carbapenemases were detected in the United States, while MbetaL-producing strains were isolated in Europe. Carbapenemase-producing Enterobacteriaceae showed high rates of resistance to most antimicrobial agents tested. The rank order of in vitro activity against these strains was as follows: tigecycline (100.0% susceptible) > polymyxin B (88.1%) > amikacin (73.0%) > imipenem (37.5%). Tigecycline was very active (MIC(90), 1 microg/ml) against this significant, contemporary collection of well-characterized strains and appears to be an excellent option compared to the polymyxins for treatment of infections caused by these multidrug-resistant Enterobacteriaceae.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Europe; Humans; Latin America; Microbial Sensitivity Tests; Minocycline; North America; Population Surveillance; 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

We report here on the activity of tigecycline and comparators against multidrug-resistant (resistant to >or=3 antimicrobial classes; MDR) Enterobacteriaceae from the USA collected between January 2004 and January 2006 as part of the Tigecycline Evaluation and Surveillance Trial (TEST). Nationally, 131 (5.9%) Escherichia coli, 174 (10.1%) Klebsiella pneumoniae, 4 (1.2%) Klebsiella oxytoca, 24 (4.9%) Enterobacter aerogenes, 126 (9.5%) Enterobacter cloacae and 20 (2.6%) Serratia marcescens isolates were MDR. Four isolates (two K. pneumoniae and two E. cloacae) were resistant to nine antimicrobials. Tigecycline performed well against MDR E. coli (MIC(90) 0.5 microg/mL, 0% resistant) and K. pneumoniae (MIC(90) 4 microg/mL, 9.2% resistant). A MIC(90) of 8 microg/mL was reported for tigecycline against the other MDR organisms studied here, notably lower than those of most comparators.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cephalosporin Resistance; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Microbial Sensitivity Tests; Minocycline; Phenotype; Population Surveillance; Quality Control; Tigecycline; United States

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Metalloproteins; Microbial Sensitivity Tests; Minocycline; Tigecycline

Topics: Drug Resistance, Bacterial; Drug Resistance, Multiple; Enterobacter aerogenes; Enterobacteriaceae Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Minocycline; Tigecycline; Urinary Tract Infections

The spread of extended-spectrum-beta-lactamase (ESBL)-producing organisms, particularly those harboring the CTX-M-type enzymes, both in the hospital and in the community, is difficult to discontinue due to the successful mobilization and evolution of the genetic elements harboring ESBL genes and coresistance rates in these isolates. The activities of tigecycline against 285 non-clonally related isolates (172 from Escherichia coli, 84 from Klebsiella spp., 20 from Enterobacter spp., 5 from Salmonella spp., and 4 from Citrobacter spp.) expressing well-characterized ESBLs and recovered in our hospital and its community area of influence were comparatively assessed (CLSI microdilution). Susceptibility rates for meropenem, imipenem, tigecycline, amikacin, and piperacillin-tazobactam were 100%, 100%, 97.5%, 93.3%, and 93%, respectively. Tigecycline (mode MIC, 0.5 microg/ml; MIC(90), 1 microg/ml) was 4- to 256-fold more active than doxycycline and minocycline (mode MIC range, 2 to 128 microg/ml). CTX-Ms were the most frequent ESBLs (61.4%), 65.8% in community and 58.6% in nosocomial isolates. CTX-M-9 (22%), CTX-M-14 (15.8%), and CTX-M-10 (14%) were the most represented derivatives. SHV and TEM variants constituted 22.8% and 15.8% of the ESBLs, respectively. Overall coresistance rates were as follows: gentamicin, 27.4%; tobramycin, 27.4%; amikacin, 6.7%; and chloramphenicol, 29.1%. Sulfonamide (61.7%), trimethoprim (52.3%), streptomycin (50.5%), and ciprofloxacin (37.2%) resistance levels were significantly (P < 0.001) associated with CTX-M-9 producers. No tigecycline resistance was observed, although seven Klebsiella pneumoniae isolates exhibited intermediate MICs (4 mug/ml). Tigecycline, lacking cross-resistance with other compounds, could represent an opportunity to reduce the intensity of selection for ESBL-producing organisms derived from the use of other antimicrobial agents. However, this in vitro promise requires support from clinical studies.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; beta-Lactams; Community-Acquired Infections; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Hospitals, University; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Minocycline; Tigecycline

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; DNA, Bacterial; England; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Microbial Sensitivity Tests; Minocycline; Polymerase Chain Reaction; Tigecycline

Steadily increasing resistance among the Enterobacteriaceae to beta-lactams, fluoroquinolones, aminoglycosides, tetracyclines, and trimethoprim/sulfamethoxazole has compromised the utility of these commonly used antimicrobial classes for many community- or hospital-acquired infections. The development of tigecycline, the sentinel representative of a novel class of broad-spectrum agents (the glycylcyclines), represents an important milestone in addressing this critical need. Resistance to tigecycline might be expected to occur via the same mechanisms that produce tetracycline resistance; however, tigecycline remains stable and largely unaffected by the commonly occurring efflux and ribosomal protection resistance mechanisms. In this study, an international collection of Enterobacteriaceae (11327 isolates; 32.8% tetracycline-resistant) from global surveillance studies (2000-2004) were evaluated against tigecycline and other comparator antimicrobials. Although the most active agents were the carbapenems and aminoglycosides (97.5-99.7% susceptible), tigecycline displayed high potency (MIC50 and MIC90, 0.25 and 1 microg/mL) with 95.7% of all strains being inhibited at < or =2 microg/mL. Despite higher MIC values observed with Serratia spp. and Proteae, between 90.5% and 97.5% of isolates were inhibited by < or =4 microg/mL of tigecycline. Tetracycline-resistant populations demonstrated only modest decreases in potency to tigecycline, which appeared to be species-dependent (up to 2-fold only for Escherichia coli, Salmonella spp., Shigella spp., and Panteoa agglomerans; and up to 4-fold for Klebsiella spp., Enterobacter spp., and Citrobacter spp.). Among E. coli (263 isolates) and Klebsiella spp. (356) that meet recognized screening definitions for extended-spectrum beta-lactamase production, 100.0% and 94.4% were inhibited by tigecycline at 2 microg/mL, respectively. These findings confirm that tigecycline exhibits potency, breadth of spectrum, and stability to the commonly occurring resistance mechanisms found in contemporary Enterobacteriaceae isolates, attributes that make this parenteral agent an attractive candidate for use against serious infections produced by these species.

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

Three patients with recurrent vascular catheter-related bacteremia were successfully treated by allowing a solution of minocycline and ethylenediaminetetraacetate (EDTA) to dwell in the lumen of the indwelling catheter or by coating polyurethane catheters with minocycline/EDTA and flushing the lumen daily with the same solution. In vitro and in vivo experiments showed that minocycline/EDTA may have broad-spectrum antimicrobial activity, may have optimal anticoagulant activity, and may be highly efficacious in preventing catheter colonization.

Topics: Adult; Anti-Bacterial Agents; Anticoagulants; Bacteremia; Catheterization, Central Venous; Drug Therapy, Combination; Edetic Acid; Enterobacter; Enterobacteriaceae Infections; Fatal Outcome; Female; Humans; Male; Middle Aged; Minocycline; Recurrence; Staphylococcal Infections