minocycline and Gram-Negative-Bacterial-Infections

Stenotrophomonas maltophilia is an opportunistic pathogen and frequent cause of serious nosocomial infections. Patient populations at greatest risk for these infections include the immunocompromised and those with chronic respiratory illnesses and prior antibiotic exposure, notably to carbapenems. Its complex virulence and resistance profile drastically limit available antibiotics, and incomplete breakpoint and pharmacokinetic/pharmacodynamic (PK/PD) data to inform dose optimization further complicates therapeutic approaches. Clinical comparison data of first-line agents, including trimethoprim-sulfamethoxazole (TMP-SMX), quinolones, and minocycline, are limited to conflicting observational data with no clear benefit of a single agent or combination therapy. Newer antibiotic approaches, including cefiderocol and aztreonam- avibactam, are promising alternatives for extensively drug-resistant isolates; however, clinical outcomes data are needed. The potential clinical utility of bacteriophage for compassionate use in treating S. maltophilia infections remains to be determined since data is limited to in-vitro and sparse in-vivo work. This article provides a review of available literature for S. maltophilia infection management focused on related epidemiology, resistance mechanisms, identification, susceptibility testing, antimicrobial PK/PD, and emerging therapeutic strategies.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Stenotrophomonas maltophilia; Trimethoprim, Sulfamethoxazole Drug Combination

This systematic review aimed to explore the recent trends in the epidemiology, risk factors, and antimicrobial susceptibility of two emerging opportunistic pathogens, Stenotrophomonas maltophilia and Elizabethkingia anophelis .. Since 2020, numerous outbreaks of S. maltophilia and E. anophelis have been reported worldwide. Most of these outbreaks have been associated with healthcare facilities, although one outbreak caused by E. anophelis in France was considered a community-associated infection. In terms of antimicrobial susceptibility, trimethoprim/sulfamethoxazole (TMP-SMZ), levofloxacin, and minocycline have exhibited good efficacy against S. maltophilia . Additionally, cefiderocol and a combination of aztreonam and avibactam have shown promising results in in vitro susceptibility testing. For E. anophelis , there is currently no consensus on the optimal treatment. Although some studies have reported good efficacy with rifampin, TMP-SMZ, piperacillin/tazobactam, and cefoperazone/sulbactam, minocycline had the most favourable in vitro susceptibility rates. Cefiderocol may serve as an alternative due to its low minimum inhibitory concentration (MIC) against E. anophelis . The role of vancomycin in treatment is still uncertain, although several successful cases with vancomycin treatment, even with high MIC values, have been reported.. Immunocompromised patients are particularly vulnerable to infections caused by S. maltophilia and E. anophelis , but the optimal treatment strategy remains inconclusive. Further research is necessary to determine the most effective use of conventional and novel antimicrobial agents in combatting these multidrug-resistant pathogens.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Cefiderocol; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Stenotrophomonas maltophilia; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

The increasing crisis regarding multidrug-resistant (MDR) and extensively drug-resistant microorganisms leads to appealing therapeutic options.. During the last 30 years, minocycline, a wide-spectrum antimicrobial agent, has been effective against MDR Gram-positive and Gram-negative bacterial infections. As with other tetracyclines, the mechanism of action of minocycline involves attaching to the bacterial 30S ribosomal subunit and preventing protein synthesis.. This antimicrobial agent has been approved for the treatment of acne vulgaris, some sexually transmitted diseases and rheumatoid arthritis. Although many reports have been published, there remains limited information regarding the prevalence, mechanism of resistance and clinical effectiveness of minocycline.. Thus, we summarize here the currently available data concerning pharmacokinetics and pharmacodynamics, mechanism of action and resistance, antibacterial activity and clinical effectiveness of minocycline.

Topics: Acne Vulgaris; Anti-Bacterial Agents; Anti-Infective Agents; Gram-Negative Bacterial Infections; Humans; Minocycline

Emergence of extensively drug-resistant (XDR) bacteria has forced clinicians to use off-label antimicrobial agents such as tigecycline. We present our experience on salvage use of tigecycline for the treatment of infections caused by XDR Gram-negative bacteria in critically ill children and review published cases.. We conducted a retrospective chart review in pediatric departments of a tertiary level hospital from January 2009 to May 2014. Patients were identified using pharmacy database. For the literature review, relevant articles were identified from PubMed.. In our case series, 13 children (7 males) with a median age of 8 years (range, 2.5 months-14 years) received tigecycline for ≥2 days as treatment for healthcare-associated infections including 5 bacteremias, 6 lower respiratory tract infections, and 3 other infections. Isolated pathogens were XDR Gram-negative bacteria except 1. A loading dose (range, 1.8-6.5 mg/kg) was given in all except 2 cases. Maintenance dose was given at 1-3.2 mg/kg q12 h. Other antimicrobials including colistin and aminoglycosides (85% and 62%, respectively) were coadministered to all patients. No serious adverse events were detected in these very ill children. Twenty cases of children treated with tigecycline were previously published, mostly for multidrug-resistant/XDR bacteria. An episode of acute pancreatitis and neutrophil engraftment delay in 2 cases were reported during tigecycline treatment. Analyzing reported and all our cases together, mortality in bloodstream infections was 86%, whereas in nonbacteremic cases it was 24% (P = .009).. Tigecycline, given at the range of administered doses as salvage therapy and in combination with other antimicrobial agents, seemed to be well tolerated in a series of mainly critically ill pediatric patients and demonstrated relatively good clinical response in nonbacteremic patients.

Topics: Adolescent; Anti-Bacterial Agents; Bacteremia; Child; Child, Preschool; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Infant; Male; Minocycline; Respiratory Tract Infections; Retrospective Studies; Tigecycline; Treatment Outcome

Urinary tract infections (UTIs) caused by antibiotic-resistant Gram-negative bacteria are a growing concern due to limited therapeutic options. Gram-negative bacteria, specifically Enterobacteriaceae, are common causes of both community-acquired and hospital acquired UTIs. These organisms can acquire genes that encode for multiple antibiotic resistance mechanisms, including extended-spectrum-lactamases (ESBLs), AmpC- β -lactamase, and carbapenemases. The assessment of suspected UTI includes identification of characteristic symptoms or signs, urinalysis, dipstick or microscopic tests, and urine culture if indicated. UTIs are categorized according to location (upper versus lower urinary tract) and severity (uncomplicated versus complicated). Increasing rates of antibiotic resistance necessitate judicious use of antibiotics through the application of antimicrobial stewardship principles. Knowledge of the common causative pathogens of UTIs including local susceptibility patterns are essential in determining appropriate empiric therapy. The recommended first-line empiric therapies for acute uncomplicated bacterial cystitis in otherwise healthy adult nonpregnant females is a 5-day course of nitrofurantion or a 3-g single dose of fosfomycin tromethamine. Second-line options include fluoroquinolones and β-lactams, such as amoxicillin-clavulanate. Current treatment options for UTIs due to AmpC- β -lactamase-producing organisms include fosfomycin, nitrofurantion, fluoroquinolones, cefepime, piperacillin-tazobactam and carbapenems. In addition, treatment options for UTIs due to ESBLs-producing Enterobacteriaceae include nitrofurantion, fosfomycin, fluoroquinolones, cefoxitin, piperacillin-tazobactam, carbapenems, ceftazidime-avibactam, ceftolozane-tazobactam, and aminoglycosides. Based on identification and susceptibility results, alternatives to carbapenems may be used to treat mild-moderate UTIs caused by ESBL-producing Enterobacteriaceae. Ceftazidime-avibactam, colistin, polymixin B, fosfomycin, aztreonam, aminoglycosides, and tigecycline are treatment options for UTIs caused by carbapenem-resistant Enterobacteriaceae (CRE). Treatment options for UTIs caused by multidrug resistant (MDR)-Pseudomonas spp. include fluoroquinolones, ceftazidime, cefepime, piperacillin-tazobactam, carbapenems, aminoglycosides, colistin, ceftazidime-avibactam, and ceftolozane-tazobactam. The use of fluoroquinolones for empiric treatment of UTIs should be restricted due to increased rat

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; beta-Lactams; Comorbidity; Drug Resistance, Bacterial; Fluoroquinolones; Fosfomycin; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Nitrofurantoin; Severity of Illness Index; Urinary Tract Infections

Antimicrobial resistance is a major and emerging threat worldwide. New antimicrobials have been unable to meet the resistance challenge, and treatment options are limited for a growing number of resistant pathogens. More and more clinicians are relying on older antimicrobials for the treatment of multidrug-resistant (MDR) bacteria. Some older antimicrobials have maintained excellent in vitro activity against highly resistant pathogens. In some instances, use of older agents is limited by unfavourable pharmacokinetic/pharmacodynamic characteristics and/or toxicities. In general, clinical data pertaining to the use of older agents for the treatment of MDR pathogens are scarce. Research efforts should be focused on the evaluation of older agents for the treatment of MDR pathogens as well as evaluating how these agents perform in complex patient populations with various and multiple co-morbid conditions.

Topics: Aminoglycosides; Anti-Bacterial Agents; Drug Combinations; Drug Resistance, Multiple, Bacterial; Fosfomycin; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Polymyxins; Sulfamethizole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

A literature review was undertaken to ascertain the molecular basis for tigecycline and colistin resistance mechanisms and the experimental basis for the detection and delineation of this resistance particularly in carbapenemase-producing Gram-negative bacteria. Pubmed, Google Scholar and Science Direct were searched with the keywords colistin, tigecycline, resistance mechanisms and detection methods. Trans-complementation and comparative MIC studies, mass spectrometry, chromatography, spectrofluorometry, PCR, qRT-PCR and whole genome sequencing (WGS) were commonly used to determine tigecycline and colistin resistance mechanisms, specifically modifications in the structural and regulatory efflux (acrAB, OqxAB, kpgABC adeABC-FGH-IJK, mexAB-XY-oprJM and soxS, rarA robA, ramRAB marRABC, adeLRS, mexRZ and nfxb) and lipid A (pmrHFIJFKLM, lpxA, lpxC lpxD and mgrB, pmrAB, phoPQ,) genes respectively. Mutations in the ribosomal 16S rRNA operon rrnBC, also yielded resistance to tigecycline through target site modifications. The mcr-1 gene conferring resistance to colistin was identified via WGS, trans-complementation and a murine thigh infection model studies. Common detection methods are mainly antibiotic sensitivity testing with broth microdilution while molecular identification tools are mostly PCR and WGS. Spectrofluorometry, MALDI-TOF MS, micro-array and real-time multiplex PCR hold much promise for the future as new detection tools.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Lipid A; Membrane Transport Proteins; Microbial Sensitivity Tests; Minocycline; Mutation; RNA, Bacterial; RNA, Ribosomal, 16S; Tigecycline

The spread of multidrug-resistant, extensively drug-resistant and pan-drug-resistant pathogens is causing an unprecedented public health crisis. The limited current therapeutic options led to the revival of two 'old' antibiotics - colistin and fosfomycin - for which a better understanding of their pharmacokinetics in the critically ill patient and in specific body compartments is required. Tigecycline's use in clinical practice for nonapproved indication based on its in vitro activity against problematic pathogens requires caution and probably higher doses. Furthermore, all three antibiotics should be used as part of combination regimens in order to prevent resistance and optimize outcomes. The development of new antibacterials in the near future, namely combinations of avibactam, ceftolozane/tazobactam and plazomicin, seems promising; however, they will only partially address current mechanisms of resistance.

Topics: Anti-Bacterial Agents; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Fosfomycin; Gram-Negative Bacterial Infections; Humans; Minocycline; Tigecycline

Tigecycline is an approved treatment for complicated skin and soft-tissue infections (cSSTIs). The efficacy of tigecycline as monotherapy or in combination with other antibacterials in the treatment of cSSTI in routine practice is described.. Individual patient-level data were pooled from five European observational studies (July 2006 to October 2011).. A total of 254 cSSTI patients who received tigecycline were included (mean age 63.2 ± 14.9 years). Of these, 34.4% were in intensive care units, 54.5% acquired their infection in hospital and 90.9% had at least one comorbidity. Infection most commonly affected the limbs (62.4%) and 43.8% of infections were classified as necrotizing. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores at the beginning of treatment were 15.0 ± 7.9 (n = 205) and 5.8 ± 3.9 (n = 32), respectively, indicating high disease severity. Staphylococcus aureus (52.7%), Escherichia coli (18.0%) and Enterococcus faecium (12.0%) were the most frequently isolated pathogens; 32.9% of infections were polymicrobial and 30.5% were due to resistant pathogens. Overall, 71.8% received tigecycline as monotherapy and 28.2% as combination therapy for a mean duration of 12 days. Clinical response rates at the end of treatment were 79.6% for all patients who received the standard dosage (183/230), 86.7% for patients who received tigecycline as monotherapy (143/165), 75.0% for patients with a nosocomial infection (96/128), 75.3% for patients with an APACHE II score >15 (61/81) and 58.3% for patients with a SOFA score ≥ 7 (7/12).. In these real-life studies, tigecycline, alone and in combination, achieved favourable clinical response rates in patients with cSSTI with a high severity of illness.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Drug Therapy, Combination; Europe; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Male; Middle Aged; Minocycline; Skin Diseases, Bacterial; Soft Tissue Infections; Tigecycline; Treatment Outcome; Young Adult

Tigecycline is a broad-spectrum antibiotic approved for the treatment of complicated intra-abdominal infections (cIAIs). The efficacy of tigecycline when administered as monotherapy or in combination with other antibacterials in the treatment of cIAIs in routine clinical practice is described.. Individual patient-level data were pooled from five European observational studies (July 2006 to October 2011).. A total of 785 cIAI patients who received tigecycline were included (mean age 63.1 ± 14.0 years). Of these, 56.6% were in intensive care units, 65.6% acquired their infection in hospital, 88.1% had at least one comorbidity and 65.7% had secondary peritonitis. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores at the beginning of treatment were 16.9 ± 7.6 (n = 614) and 7.0 ± 4.2 (n = 108), respectively, indicating high disease severity. Escherichia coli (41.8%), Enterococcus faecium (40.1%) and Enterococcus faecalis (21.1%) were the most frequently isolated pathogens; 49.1% of infections were polymicrobial and 17.5% were due to resistant pathogens. Overall, 54.8% (n = 430) received tigecycline as monotherapy and 45.2% (n = 355) as combination therapy for a mean duration of 10.6 days. Clinical response rates at the end of treatment were 77.4% for all patients (567/733), 80.6% for patients who received tigecycline as monotherapy (329/408), 75.2% for patients with a nosocomial infection (354/471), 75.8% for patients with an APACHE II score >15 (250/330) and 54.2% (32/59) for patients with a SOFA score ≥ 7.. In these real-life studies, tigecycline, alone and in combination, achieved favourable clinical response rates in patients with cIAI with a high severity of illness.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Drug Therapy, Combination; Europe; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Intraabdominal Infections; Male; Middle Aged; Minocycline; Tigecycline; Treatment Outcome; Young Adult

The treatment of infections caused by multidrug-resistant Gram-negative bacteria is challenging given the limited options for effective therapy. Combination therapy has garnered great interest recently, with the goals of ensuring appropriate therapy with at least one active agent, and achieving synergistic activity among the anti-microbials used. In this review, we evaluate the data supporting the use of combination therapy against Pseudomonas aeruginosa, carbapenem-resistant Enterobacteriaceae, Acinetobacter species and Stenotrophomonas maltophilia. Various regimens have been tried with promising results; however, the data are mostly derived from in vitro synergy studies. While these reports suggest an advantage of combination therapy over monotherapy, clinical data are scarce, and are comprised of retrospective and a few prospective observational studies. Well-designed randomized trials are needed to better elucidate the efficacy of the various combination regimens. Until then, this review offers a critical appraisal of the published literature and provides recommendations based on the available evidence.

Topics: Anti-Bacterial Agents; Carbapenems; Clinical Trials as Topic; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Fluoroquinolones; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Minocycline; Polymyxins; Tigecycline; Trimethoprim, Sulfamethoxazole Drug Combination

The emergence of resistant to carbapenems Gram-negative bacteria (CR GNB) has severely challenged antimicrobial therapy. Many CR GNB isolates are only susceptible to polymyxins; however, therapy with polymyxins and other potentially active antibiotics presents some drawbacks, which have discouraged their use in monotherapy. In this context, along with strong pre-clinical evidence of benefit in combining antimicrobials against CR GNB, the clinical use of combination therapy has been raised as an interesting strategy to overcome these potential limitations of a single agent. Polymyxins, tigecycline and even carbapenems are usually the cornerstone agents in combination schemes. Optimization of the probability to attain the pharmacokinetic/pharmacodynamic targets by both cornerstone drug and adjuvant drug is of paramount importance to achieve better clinical and microbiological outcomes. Clinical evidence of the major drugs utilized in combination schemes and how they should be prescribed considering pharmacokinetic/pharmacodynamic characteristics against CR GNB will be reviewed in this article.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenems; Drug Administration Schedule; Drug Dosage Calculations; Drug Synergism; Drug Therapy, Combination; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Minocycline; Polymyxins; Tigecycline

Tigecycline is a broad-spectrum antibiotic with activity against difficult-to-treat pathogens such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus spp., Acinetobacter baumannii, and Gram-negative bacterial strains that produce extended-spectrum β-lactamases. Minimal organ toxicity and lack of dosage adjustment in most patients are important considerations for tigecycline use. Tigecycline has been shown to be as effective and safe as standard antimicrobial therapy for treatment of adults with complicated intra-abdominal infections, complicated skin and skin structure infections, and community-acquired bacterial pneumonia. The clearest applications of tigecycline are for on-label indications. Whether tigecycline should be utilized as therapy for other infections including hospital-acquired infections with a high likelihood of multidrug-resistant pathogens is a complex issue that requires ongoing assessment. This article offers an updated overview of tigecycline clinical studies, current microbial resistance patterns, pharmacokinetic/pharmacodynamic investigations, and safety analyses.

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Intraabdominal Infections; Minocycline; Pneumonia, Bacterial; Skin Diseases, Bacterial; Tigecycline

Antibacterial drug discovery and development has slowed considerably in recent years, with novel classes discovered decades ago and regulatory approvals tougher to get. Traditional approaches and the newer genomic mining approaches have not yielded novel classes of antibacterial compounds. Instead, improved analogues of existing classes of antibacterial drugs have been developed by improving potency, minimizing resistance and alleviating toxicity.. This article is a comprehensive review of newer classes of antibacterial drugs introduced or approved after year 2000.. It describes their mechanisms of action/resistance, improved analogues, spectrum of activity and clinical trials. It also discusses new compounds in development with novel mechanisms of action, as well as novel unexploited bacterial targets and strategies that may pave the way for combating drug resistance and emerging pathogens in the twenty-first century.. The outlook of antibacterial drug discovery, though challenging, may not be insurmountable in the years ahead, with legislation on incentives and funding introduced for developing an antimicrobial discovery program and efforts to conserve antibacterial drug use.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Carbapenems; Drug Delivery Systems; Drug Discovery; Drug Evaluation, Preclinical; Drug Resistance, Bacterial; Drugs, Investigational; Glycopeptides; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Macrolides; Minocycline; Oxazolidinones; Tigecycline

The emergence of multidrug-resistant (MDR) Gram-negative bacilli creates a big problem for the treatment of nosocomial infections. As the pharmaceutical pipeline wanes, the only therapeutic options are two revived antibacterials (colistin and fosfomycin), a newer one (tigecycline) and an early-phase neoglycoside (ACHN-490). Polymyxins, known since 1947, are mostly represented by polymyxin E (colistin), which has recently gained a principal position in the management of the most difficult-to-treat MDR Gram-negative pathogens -Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae. However, despite promising therapeutic results in 59-75% of cases, the reported studies share common drawbacks, i.e. the absence of a control group, their retrospective nature, variable dosing and duration of therapy, simultaneous administration of other antibiotics in >70% and a lack of resistance development monitoring. The necessity for well-designed prospective clinical trials is therefore urgent. Fosfomycin is active in vitro against MDR Enterobacteriaceae, including a high proportion of P. aeruginosa; however, clinical experience is lacking with the parenteral formulation in MDR infection and on the best combinations to prevent resistance development. Tigecycline, which is active against MDR Enterobacteriaceae and A. baumannii, has shown satisfactory clinical experience. However, dosage adjustment is required because of low blood levels. ACHN-490, which has promising in vitro activity against MDR K. pneumoniae, is still in early phase II trials in urinary tract infections. Meanwhile, the strict application of infection control measures is the cornerstone of nosocomial infection prevention, and antibiotic stewardship, exemplified by appropriate duration of therapy and de-escalation policies, should not be overlooked.

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Fosfomycin; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Minocycline; Randomized Controlled Trials as Topic; Tigecycline; Treatment Outcome

Tigecycline has been investigated in combination with other antibacterials against a wide range of susceptible and multiresistant Gram-positive and Gram-negative bacteria. Combinations have been analysed in vitro, in animal models and in human case reports. In vitro, tigecycline combined with other antimicrobials produces primarily an indifferent response (neither synergy nor antagonism). Nevertheless, synergy occurred when tigecycline was combined with rifampicin against 64-100% of Enterococcus spp., Streptococcus pneumoniae, Enterobacter spp. and Brucella melitensis isolates. Combinations of tigecycline with amikacin also showed synergy for 40-100% of Enterobacter spp., Klebsiella pneumoniae, Proteus spp. and Stenotrophomonas maltophilia isolates. Moreover, bactericidal synergisms occurred with tigecycline plus amikacin against problematic Acinetobacter baumannii and Proteus vulgaris, and with colistin against K. pneumoniae. Data from animal experiments and case reports, although limited, displayed consistent beneficial activity of tigecycline in combination with other antibacterials against multiresistant organisms, including vancomycin against penicillin-resistant S. pneumoniae in experimental meningitis, gentamicin against Pseudomonas aeruginosa in experimental pneumonia, daptomycin against Enterococcus faecium endocarditis, and colistin against K. pneumoniae bacteraemia and P. aeruginosa osteomyelitis. Antagonism was extremely rare in vitro and was not reported in vivo. Thus, tigecycline may be combined with a second antimicrobial as part of a combination regimen.

Topics: Animals; Anti-Bacterial Agents; Drug Synergism; Drug Therapy, Combination; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Microbial Viability; Minocycline; Tigecycline

Rapid emergence of resistance against antibacterials emphasizes the need for the development of novel and/or more potent antibacterials. Tigecycline is the first representative of a new drug class, the glycylcyclines, and was approved in 2005 by the US FDA for the treatment of complicated skin and skin structure infections, as well as complicated intra-abdominal infections. Tigecycline distributes extensively into the intracellular space of tissue and accumulates in cells, which may qualify it for the treatment of intracellular infections. The pharmacokinetics of tigecycline are complex with both linear and non-linear characteristics. The reason for this complexity is still not fully understood. Non-linearity can be found in the volume of distribution possibly due to extensive and variable tissue and/or plasma protein binding. In contrast, clearance and area under the plasma concentration-time curve are dose-independent. Tigecycline has a high incidence of mild adverse effects, mainly nausea and vomiting, but is otherwise well tolerated.

Topics: Animals; Anti-Bacterial Agents; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Minocycline; Tigecycline

The emergence of multidrug-resistant (MDR) Gram-negative bacilli creates a challenge in the treatment of nosocomial infections. While the pharmaceutical pipeline is waning, two revived old antibacterials (colistin and fosfomycin), a newer one (tigecycline) and an 'improved' member of an existing class (doripenem) are the only therapeutic options left. The class of polymyxins, known since 1947 and represented mostly by polymyxin B and polymyxin E (colistin), has recently gained a principal role in the treatment of the most problematic MDR Gram-negative pathogens (such as Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae and Stenotrophomonas maltophilia). Future prospective studies are needed to answer important clinical questions, such as the possible benefit of combination with other antimicrobials versus monotherapy, the efficacy of colistin in neutropenic hosts and the role of inhaled colistin. As new pharmacokinetic data emerge, clarification of the pharmacokinetic/pharmacodynamic (PK/PD) profile of colistin as well as appropriate dosing seems urgent, while development of resistance must be carefully monitored. Fosfomycin tromethamine, a synthetic salt of fosfomycin discovered in 1969, has regained attention because of its in vitro activity against extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae and MDR P. aeruginosa. Although in use for decades in oral and parenteral formulations for a variety of infections without significant toxicity, its clinical utility in MDR infections remains to be explored in future studies. Tigecycline, the first representative of the new class of glycylcyclines, holds promise in infections from MDR K. pneumoniae (K. pneumoniae carbapenemase [KPC]- and ESBL-producing strains) and Enterobacteriaceae with various mechanisms of resistance. The in vitro activity of tigecycline against A. baumannii makes it a tempting option, as it is currently the most active compound against MDR strains along with colistin. However, the usual minimum inhibitory concentration values of this pathogen are approximately 2 mg/L and compromise clinical outcomes based on PK/PD issues. Its advantageous penetration into various tissues is useful in infections of the skin and soft tissues as well as intra-abdominal infections (official indications), whereas low serum concentrations compromise its use in bloodstream infections. Therefore, prospective studies with dose escalation are urgently needed, as well as clar

Topics: Anti-Bacterial Agents; Carbapenems; Doripenem; Drug Resistance, Multiple, Bacterial; Fosfomycin; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Minocycline; Polymyxins; Tigecycline

Tigecycline is a glycylcycline antibacterial agent derived from minocycline with a broad spectrum of activity. Like tetracycline agents, it inhibits bacterial protein synthesis but is able to bind to target sites with higher affinity and overcome tetracycline-resistance mechanisms due to structural modifications. The safety and efficacy of tigecycline has been demonstrated in clinical trials for complicated intra-abdominal and complicated skin and skin-structure infections. It has received approval for these indications in several countries, including the USA in 2005, and European Union in 2006. Aside from approved indications and in vitro data, growing clinical experience suggests a potential role for tigecycline in the management of multi-drug resistant infections due to drug-resistant pathogens. Further study is necessary to determine the ultimate role of tigecycline in treating these types of infections.

Topics: Anti-Bacterial Agents; Clinical Trials as Topic; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Gram-Positive Cocci; Humans; Minocycline; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Skin Diseases, Bacterial; Soft Tissue Infections; Tigecycline; Treatment Outcome

Although much of today's media focuses on multidrug-resistant gram-positive bacteria such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus, resistance within gram-negative bacilli continues to rise, occasionally creating situations in which few or no antibiotics that retain activity are available. Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella sp are emerging threats nationally. Although carbapenems are considered the antibiotic class of choice to treat ESBL-producing Enterobacteriaceae, the ability of these organisms to produce carbapenemases has now become apparent in some regions throughout the United States. Although still rare, Klebsiella sp that produce KPC-2 retain susceptibility only to tigecycline, polymyxins, and occasionally aminoglycosides. Multidrug resistance among Pseudomonas aeruginosa and Acinetobacter sp has always been apparent across many hospitals in the United States. Recent surveillance indicates increasing resistance to all currently available antibiotics, including carbapenems, cephalosporins, penicillins, fluoroquinolones, and aminoglycosides. Against many strains, only polymyxins retain activity; however, resistance has also been reported to these agents. Fortunately, resistance mechanisms such as metallo-beta-lactamases are still rare in the United States. As no new antibiotics with novel mechanisms against many of these gram-negative bacilli are expected to be developed in the foreseeable future, careful and conservative use of agents combined with good infection control practices is required.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Carbapenems; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Minocycline; North America; Polymyxins; Sulbactam; Tigecycline

Tigecycline, the first-in-class glycylcycline, was developed to recapture the broad spectrum of activity of the tetracycline class and to treat patients with difficult-to-treat bacterial infections. Tigecycline's in vitro spectrum of activity encompasses aerobic, facultative and anaerobic Gram-positive and -negative bacteria, including antimicrobial-resistant bacteria such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis and Enterococcus faecium, and extended-spectrum beta-lactamase-producing Enterobacteriaceae. Clinical trials involving patients with complicated skin and skin-structure infections and complicated intra-abdominal infections, including patients infected with methicillin-resistant S. aureus, demonstrated that tigecycline was bacteriologically and clinically effective with mild-to-moderate gastrointestinal adverse events (i.e., nausea, vomiting and diarrhea) the most commonly reported. Tigecycline is a promising new broad-spectrum parenteral monotherapy for the treatment of patients with Gram-positive and -negative bacterial infections.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacteria, Aerobic; Bacteria, Anaerobic; Clinical Trials as Topic; Drug Resistance, Bacterial; Female; Gastrointestinal Diseases; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Skin Diseases, Bacterial; Tigecycline; Treatment Outcome

Nitrofurantoin, amikacin, colistin, polymyxin B, doxycycline, and minocycline are antibiotics with proven effectiveness against selected pathogens. These antibiotics have not developed resistance over time. As "low-resistance potential antibiotics" that are effective against an increasing number of infections due to resistant gram-positive or gram-negative pathogens, these antimicrobials remain an important part of the antibiotic armamentarium. They will be used increasingly in the future, as highly resistant organisms continue to be important clinically and therapeutic options remain limited.

Topics: Amikacin; Cell Membrane; Colistin; Doxycycline; Drug Resistance, Microbial; Gram-Negative Bacterial Infections; Humans; Methicillin Resistance; Minocycline; Nitrofurantoin; Polymyxin B; Staphylococcal Infections; Urinary Tract Infections

Tigecycline, is a novel broad-spectrum glycylcycline antibiotic, which has activity against a broad range of Gram-positive, Gram-negative, atypical, anaerobic and antibiotic-resistant bacteria. This includes activity against MRSA, VRE and penicillin resistant Streptococcus pneumoniae. Whilst exhibiting antibacterial activities typical of earlier tetracyclines, it has more potent activity against tetracycline-resistant organisms. Although a bacteriostatic compound in vitro, its effectiveness in clinical trials suggests that traditional laboratory thinking about using bacteriostatic drugs in serious infections needs to be revised. Unlike existing tetracyclines, tigecycline is only available as an intravenous preparation, is administered twice daily although its long half life and post-antibiotic effect may make once daily dosing possible, appears to have good tissue penetration (e.g. skin) and requires no adjustment in the presence of renal or hepatic diseases. It is efficacious in complicated skin and soft tissue infections and in intra-abdominal infections. In three trials, it was well tolerated despite increased frequency of nausea and vomiting. In the light of these early clinical data and the likelihood that this agent will become available for clinical use within the next 12-24 months, this review aims to summarise the key clinical data and potential formulary considerations for the future use of this agent, subject to further clinical trials and publication of clinical human data.

Topics: Anti-Bacterial Agents; Clinical Trials as Topic; Drug Resistance, Bacterial; Formularies as Topic; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Minocycline; Tigecycline

The increasing identification of antibiotic-resistant pathogens that cause serious infections cannot be ignored. Although the future cannot be predicted with certainty, it is surely possible that an extensive epidemic of resistant bacterial infections could potentially harm millions of people. Given that it takes more than 10 years to establish the efficacy and safety of new compounds, there is an urgent need to restock the antibiotic pipeline. Only a few new antibacterial agents have received approval by the US Food and Drug Administration in the last 5 years, including linezolid in 2001, cefditoren, pivoxil and ertapenem in 2002, gemifloxacin and daptomycin in 2003, and telithromycin in 2004. Many of these agents are improved derivatives from established classes of antibiotics, and several are directed primarily at resistant Gram-positive bacteria (e.g., linezolid and daptomycin). One promising new addition is the recent approval of tigecycline (Tigacyl, Wyeth) in June 2005.

Topics: Animals; Anti-Bacterial Agents; Drug Resistance, Microbial; Gram-Negative Bacterial Infections; Humans; Minocycline; Technology, Pharmaceutical; Tigecycline

Chryseobacterium meningosepticum is a ubiquitous Gram-negative bacillus historically associated with meningitis in premature neonates. We report 15 positive cultures and 6 cases of infection among immunocompromised adults at our institution over a 10-year period and review the English-language literature on C. meningosepticum. Excluding the present series, there are 308 reports of positive cultures in the literature, of which 59% were determined to represent true infections. Sixty-five percent of those infected were younger than 3 months of age. Meningitis was the most common infectious syndrome among neonates, seen in 84% of cases and associated with a 57% mortality rate. Less commonly reported infections among infants included sepsis (13%) and pneumonia (3%). Pneumonia was the most frequent infection among the postneonatal group, accounting for 40% of cases, followed by sepsis (24%), meningitis (18%), endocarditis (3%), cellulitis (3%), abdominal infections (3%), eye infections (3%), and single case reports of sinusitis, bronchitis, and epididymitis. The 6 cases in our series were all adults, with a mean age of 58.7 years. Sites of C. meningosepticum infection were limited to the lungs, bloodstream, and biliary tree. Infection in our series was associated with prolonged hospitalization, prior exposure to multiple antibiotics, and host immunocompromise, particularly neutropenia. C. meningosepticum is resistant to multiple antibiotics, and disk dilution is notoriously unreliable for antibiotic sensitivity testing. Sensitivity testing on the 15 isolates from our institution revealed the most efficacious antibiotics to be minocycline (100% sensitive), rifampin (93%), trimethoprim-sulfamethoxazole (67%), and ciprofloxacin (53%). In contrast to reports in the literature, the isolates in our series displayed widespread resistance to vancomycin (100% resistant or intermediately sensitive), erythromycin (100%), and clindamycin (86%). These findings have important implications for the clinician when choosing empiric antibiotic regimens for patients with risk factors for C. meningosepticum infection.

Topics: Adult; Aged; Anti-Bacterial Agents; Antibiotics, Antitubercular; Breast Neoplasms; Ciprofloxacin; Drug Resistance, Microbial; Female; Flavobacterium; Gram-Negative Bacterial Infections; Humans; Immunocompromised Host; Infant; Infant, Newborn; Leukemia, Myeloid, Acute; Liver Transplantation; Male; Meningitis, Bacterial; Middle Aged; Minocycline; Pneumonia, Bacterial; Rifampin; Sepsis; Trimethoprim, Sulfamethoxazole Drug Combination

Tigecycline (TGC), a glycylcycline, has expanded activity against Gram-positive and Gram-negative, anaerobic, and atypical bacteria. Two phase 3 studies were conducted. Hospitalized patients with community-acquired pneumonia (CAP) were randomized to intravenous (IV) TGC (100 mg followed by 50 mg bid) or IV levofloxacin (LEV) (500 mg bid). In 1 study, patients could be switched to oral LEV after at least 3 days intravenously. The coprimary efficacy end points were as follows: clinical response in clinically evaluable (CE) and clinical modified intent-to-treat (c-mITT) populations at test-of-cure (TOC). The secondary end points were as follows: microbiologic efficacy and susceptibility to TGC for CAP bacteria. Safety evaluations were included. Eight hundred ninety-one were patients screened: 846 mITT (TGC 424, LEV 422), 574 CE (TGC 282, LEV 292). Most patients had Fine Pneumonia Severity Index II to IV (80.7% TGC, 74.4% LEV, mITT). At TOC (CE), TGC cured 253/282 patients (89.7%) and LEV cured 252/292 patients (86.3%); the absolute difference of TGC-LEV was 3.4% (95% confidence interval [CI], -2.2 to 9.1, noninferior [P < 0.001]). In c-mITT, TGC cured 319/394 patients (81.0%) and LEV cured 321/403 patients (79.7%); the absolute difference of TGC-LEV was 1.3% (95% CI -4.5 to 7.1, noninferior [P < 0.001]). The drug-related adverse events (AEs) of nausea (20.8% TGC versus 6.6% LEV) and vomiting (13.2% TGC versus 3.3% LEV) were significantly higher in TGC; elevated alanine aminotransferase (2.8% TGC versus 7.3% LEV) and aspartate aminotransferase (2.6% TGC versus 6.9% LEV) were significantly higher in LEV. Discontinuations for AEs were low (TGC, 26 patients [6.1%]; LEV, 34 patients [8.1%]). TGC appeared safe and achieved cure rates similar to LEV in hospitalized patients with CAP.

Topics: Adult; Aged; Anti-Bacterial Agents; Community-Acquired Infections; Female; Gram-Negative Bacterial Infections; Haemophilus Infections; Humans; Levofloxacin; Liver Function Tests; Male; Middle Aged; Minocycline; Ofloxacin; Pneumococcal Infections; Pneumonia, Bacterial; Tigecycline; Treatment Outcome

We evaluated a catheter-lock solution consisting of N-acetylcysteine, tigecycline, and heparin for catheter salvage in patients with hemodialysis catheter-associated bacteremia. Eighteen case patients received the catheter-lock solution for 14 days plus systemic antibiotic therapy. Treatment was successful for 15 (83%) of the 18 case patients within 90 days of follow-up, with a median catheter retention interval of 64.5 days.

Topics: Acetylcysteine; Anti-Bacterial Agents; Bacteremia; Catheterization; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Male; Middle Aged; Minocycline; Pilot Projects; Prospective Studies; Renal Dialysis; Tigecycline; Treatment Outcome

Exposure-response analyses were performed to test the microbiological and clinical efficacies of tigecycline in complicated intra-abdominal infections where Escherichia coli and Bacteroides fragilis are the predominant pathogens. Data from evaluable patients enrolled in three clinical trials were pooled. Patients received intravenous tigecycline (100-mg loading dose followed by 50 mg every 12 h or 50-mg loading dose followed by 25 mg every 12 h). At the test-of-cure visit, microbiological and clinical responses were evaluated. Patients were prospectively classified into cohorts based on infection with a baseline pathogen(s): E. coli only (cohort 1), other mono- or polymicrobial Enterobacteriaceae (cohort 2), at least one Enterobacteriaceae pathogen plus an anaerobe(s) (cohort 3), at least one Enterobacteriaceae pathogen plus a gram-positive pathogen(s) (cohort 4), and all other pathogens (cohort 5). The cohorts were prospectively combined to increase sample size. Logistic regression was used to evaluate ratio of steady-state 24-hour area under the concentration-time curve (AUC) to MIC as a response predictor, and classification-and-regression-tree (CART) analyses were utilized to determine AUC/MIC breakpoints. Analysis began with cohorts 1, 2, and 3 pooled, which included 71 patients, with 106 pathogens. The small sample size precluded evaluation of cohorts 1 (34 patients, 35 E. coli pathogens) and 2 (16 patients, 24 Enterobacteriaceae). CART analyses identified a significant AUC/MIC breakpoint of 6.96 for microbiological and clinical responses (P values of 0.0004 and 0.399, respectively). The continuous AUC/MIC ratio was also borderline predictive of microbiological response (P = 0.0568). Cohort 4 (21 patients, 50 pathogens) was evaluated separately; however, an exposure-response relationship was not detected; cohort 5 (31 patients, 60 pathogens) was not evaluated. The prospective approach of creating homogenous populations of pathogens was critical for identifying exposure-response relationships in complicated intra-abdominal infections.

Topics: Abdominal Cavity; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Area Under Curve; Bacteria, Anaerobic; Double-Blind Method; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Tigecycline; Treatment Outcome

Topics: Anti-Bacterial Agents; Bacteremia; Drug Administration Schedule; Drug Resistance, Multiple; Gram-Negative Bacterial Infections; Humans; Minocycline; Tigecycline

Stenotrophomonas maltophilia is an emerging opportunistic pathogen for which there are limited therapeutic options because of intrinsic multidrug resistance. S. maltophilia isolates were collected as part of the Antimicrobial Testing Leadership and Surveillance (ATLAS) program and minimum inhibitory concentrations (MICs) were determined using broth microdilution methods. Susceptibility was interpreted according to Clinical and Laboratory Standards Institute (CLSI) breakpoints. Isolates with tigecycline MIC ≤2 mg/L were defined as susceptible, using the United States Food and Drug Administration criteria of Enterobacterales. A total of 2330 S. maltophilia isolates were collected from 47 countries worldwide in the ATLAS program from 2004 to 2020. Most patients were hospitalized (92.3%, 2151/2330) and respiratory tract infections (47.8%, 1114/2330) were the most common source of isolates. Minocycline had the highest susceptibility rate (98.8%), followed by levofloxacin (85.0%), trimethoprim-sulfamethoxazole (TMP-SMX) (84.4%), and ceftazidime (53.7%). A total of 98.3% (2290/2330) of S. maltophilia isolates had tigecycline MIC ≤2 mg/L. Among the S. maltophilia isolates exhibiting resistance to levofloxacin and ceftazidime, 89.3% (150/168) and 97.3% (692/711), respectively, were susceptible to tigecycline. Eight countries provided more than 30 isolates and were selected for comparison. Geographical difference in antimicrobial resistance was significant for levofloxacin, minocycline, and tigecycline (all P<0.05) but not for ceftazidime (P=0.467). These in vitro data demonstrated that minocycline had a higher susceptibility rate than levofloxacin and ceftazidime, and that tigecycline could be an alternative or salvage option for the treatment of S. maltophilia infections.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Ceftazidime; Gram-Negative Bacterial Infections; Humans; Leadership; Levofloxacin; Microbial Sensitivity Tests; Minocycline; Stenotrophomonas maltophilia; Tigecycline

Evaluate methods for identification and typing of Stenotrophomonas maltophilia isolated from a pharmaceutical facility.. From 270 S. maltophilia strains identified by VITEK®2, 40 were selected and submitted to MALDI TOF-MS, 16S and 23S rRNA gene analysis, enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR), and an antimicrobial susceptibility profile. 16S rRNA sequencing was able to identify 39 (97.5%) strains as Stenotrophomonas spp. and one (2.5%) as Luteimonas huabeiensis. MALDI TOF-MS identified 37 (92.5%) strains as S. maltophilia, and three (7.5%) were not identified. PCR targeting 23S rRNA yielded a positive result for 39 (97.5%) strains. However, after sequencing, two strains were identified as Stenotrophomonas rhizophila, showing false-positive results. The confirmed S. maltophilia strains (n = 37) showed 35 distinct ERIC-PCR profiles and exhibited sensitivity to minocycline and levofloxacin, and six (16.3%) showed intermediate resistance to sulfamethoxazole-trimethoprim.. Matrix-assisted laser desorption lonization-time of flight mass spectrometry (MALDI-TOF MS) was a satisfactory methodology for the identification of S. maltophilia, but expansion of the database is necessary for the identification of other species. 16S rDNA sequencing showed low resolution for Stenotrophomonas species differentiation. PCR targeting 23S rRNA could not differentiate S. maltophilia from S. rhizophila. ERIC-PCR was shown to be a useful tool for the microbial source tracking of S. maltophilia.

Topics: Anti-Bacterial Agents; Gram-Negative Bacterial Infections; Humans; Levofloxacin; Microbial Sensitivity Tests; Minocycline; RNA, Ribosomal, 16S; Stenotrophomonas maltophilia; Trimethoprim, Sulfamethoxazole Drug Combination

The minocycline susceptibility of 3,856 isolates including

Topics: Anti-Bacterial Agents; Burkholderia cepacia complex; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Stenotrophomonas maltophilia

The historical treatment of choice for Stenotrophomonas maltophilia infection is trimethoprim/sulfamethoxazole and this is primarily based on preclinical studies. The objective of this study was to examine the clinical outcomes of patients receiving monotherapy with different agents.. This was a retrospective study of adult patients receiving monotherapy for S. maltophilia infection with trimethoprim/sulfamethoxazole (TMP/SMX), a fluoroquinolone, or minocycline from 2010 to 2016. The primary outcome was clinical failure, a composite of recurrence, alteration of therapy due to adverse reaction or concern for clinical failure, or 30-day in-hospital mortality. The secondary outcome was 30-day in-hospital mortality. To account for treatment selection bias, multivariate regression and propensity score weighting were conducted.. 284 patients were included (217 received TMP/SMX, 28 received a fluoroquinolone, and 39 received minocycline). The TMP/SMX and minocycline groups appeared to include similar patients whereas the fluoroquinolone group appeared to represent a slightly less severely ill population. Clinical failure was similar between groups (36%, 29%, and 31% in the TMP/SMX, fluoroquinolone, and minocycline groups, respectively, P=0.69) as was 30-day mortality (15%, 7%, and 5% in the TMP/SMX, fluoroquinolone, and minocycline groups, respectively, P=0.16). After controlling for confounding factors, receipt of minocycline (adjusted odds ratio [OR]=0.2 [0.1-0.7]) but not a fluoroquinolone (adjusted OR=0.3 [0.1 to 2.1]) was associated with lower mortality compared with TMP/SMX. This association persisted after propensity score weighting.. Outcomes were similar or better with alternatives to TMP/SMX monotherapy, which indicates this may not be the treatment of choice for infections caused by S. maltophilia.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cohort Studies; Drug Resistance, Multiple, Bacterial; Female; Fluoroquinolones; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Minocycline; Retrospective Studies; Stenotrophomonas maltophilia; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Stenotrophomonas maltophilia (S. maltophilia) is an important opportunistic pathogen that can be isolated in hospitals. With the abuse of broad spectrum antibiotics and invasive surgical devices, the rate of S. maltophilia infection is increasing every year. This study was an epidemiological analysis of the clinical and molecular characteristics of S. maltophilia infection in a Chinese teaching hospital. The goal was to obtain a comprehensive understanding of the status of S. maltophilia infection to provide strong epidemiological data for the prevention and treatment of S. maltophilia infection.. A total of 93 isolates from Renji Hospital affiliated with the Shanghai Jiaotong University School of Medicine were included, in which 62 isolates were from male patients. In addition, 81 isolates were isolated from sputum samples. A total of 86 patients had underlying diseases. All patients received antibiotics. Multilocus sequence typing (MLST) analysis indicated that 61 different sequence types (STs) were found (including 45 novel STs), and MLST did not show significantly dominant STs. Pulsed field gel electrophoresis (PFGE) results showed that 93 isolates could be divided into 73 clusters, and they also showed weak genetic linkages between isolates. The resistant rates to trimethoprim/sulfamethoxazole (TMP/SMX) and levofloxacin were 9.7 and 4.3%, respectively, and all isolates were susceptible to minocycline. Four virulence gene's loci Stmpr1, Stmpr2, Smf-1, and Smlt3773 were positive in 79.6, 91.4, 94.6, and 52.7% of the isolates, respectively. Three biofilm genes rmlA, spgM, and rpfF were positive in 82.8, 92.5, and 64.5% of the isolates, respectively. Mean biofilm forming level of OD. Most of the patients had prior medical usage histories and baseline diseases. The positive rate of virulence genes was high, the drug resistance rate of S. maltophilia was low, and the biofilm formation ability was strong. The increased use of antibiotics was an independent risk factor for S. maltophilia infection, which should receive more attention. No obvious clonal transmissions were found in the same departments.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Typing Techniques; Biofilms; Case-Control Studies; China; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Gene Expression; Genes, Bacterial; Gram-Negative Bacterial Infections; Hospitals, Teaching; Humans; Intensive Care Units; Levofloxacin; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Molecular Epidemiology; Multilocus Sequence Typing; Opportunistic Infections; Retrospective Studies; Risk Factors; Stenotrophomonas maltophilia; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Disease-Free Survival; Female; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Minocycline; Neoplasms; Retrospective Studies; Risk Factors; Stenotrophomonas maltophilia; Survival Rate; Tertiary Care Centers; Trimethoprim, Sulfamethoxazole Drug Combination

The aim of this study was to determine the usefulness of tigecycline in combination treatment of Stenotrophomonas\ maltophilia infections by evaluating the in vitro synergistic effects of tigecycline with various antibiotics using the E-test method.. Synergy testing by E-test was performed with various antibiotic combinations in 10 S. maltophilia isolates\ identified as a cause of infection. The antibiotics used in the study included tigecycline (TGC), cefoperazone-sulbactam (CPS),\ ceftazidime (TZ), levofloxacin (LEV), and trimethoprim-sulfamethoxazole (cotrimoxazole) (TS). Four different combinations (TGCCPS,\ TGC-TZ, TGC-LEV, TGC-TS) were studied with the E-test synergy method.. S. maltophilia isolates were found to have the highest level of susceptibility to trimethoprim-sulfamethoxazole, tigecycline, and\ levofloxacin. The fractional inhibitory concentration (FIC) index was calculated as FIC = MICAB/MICA + MICBA/MICB. The FIC\ index values were calculated and classified as synergistic (FIC < 0.5), additive (FIC = 0.5–1), indifferent (FIC = 1–4), and antagonistic\ (FIC > 4). According to FIC index values, synergy was found with the highest rate with TGC-CPS and TGC-LEV combinations (20%).\ Antagonistic activity was not found in any combination.. When trimethoprim-sulfamethoxazole cannot be used because of resistance or allergy, tigecycline alone or in combination\ may be included as an alternative option. Although in vitro results are promising, clinical data are required.

Topics: Anti-Infective Agents; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Gram-Negative Bacterial Infections; Humans; In Vitro Techniques; Levofloxacin; Microbial Sensitivity Tests; Minocycline; Stenotrophomonas maltophilia; Tigecycline; Trimethoprim, Sulfamethoxazole Drug Combination

Stenotrophomonas maltophilia is a gram-negative opportunistic bacterium that may cause a myriad of clinical diseases in immunocompromised individuals. We aimed to describe the clinical characteristics, risk factors, mortality, and treatment of S. maltophilia bacteremia in critically ill children, a topic on which data are sparse.. A multicenter observational retrospective study in which medical charts of critically ill children with S. maltophilia bacteremia were reviewed between 2012 and 2017.. Data were collected from each of the four largest PICUs nationwide, allocated in tertiary medical centers to which children with complex conditions are referred regularly.. A total of 68 suitable cases of S. maltophilia bacteremia were retrieved and reviewed.. The total occurrence rate of S. maltophilia isolation had increased significantly during the study period (r = 0.65; p = 0.02). The crude mortality was 42%, and the attributed mortality was 18%. Significant risk factors for mortality were a longer length of hospital stay prior to infection (33 d in nonsurvivors vs 28 in survivors; p = 0.03), a nosocomial source of infection (p = 0.02), presentation with septic shock (p < 0.001), and treatment with chemotherapy (p = 0.007) or carbapenem antibiotics (p = 0.05) prior to culture retrieval. On multivariate analysis, septic shock (odds ratio, 14.6; 95% CI, 1.45-147.05; p = 0.023) and being treated with chemotherapy prior to infection (odds ratio, 5.2; 95% CI, 1.59-17.19; p = 0.006)] were associated with mortality. The combination of ciprofloxacin, trimethoprim-sulfamethoxazole, and minocycline resulted in the longest survival time (p < 0.01).. The significant attributed mortality associated with S. maltophilia bacteremia in critically ill children calls for an aggressive therapeutic approach. The findings of this investigation favor a combination of trimethoprim-sulfamethoxazole, ciprofloxacin, and minocycline.

Topics: Anti-Bacterial Agents; Child; Child, Preschool; Ciprofloxacin; Comorbidity; Critical Illness; Drug Combinations; Female; Gram-Negative Bacterial Infections; Humans; Immunocompromised Host; Infant; Intensive Care Units, Pediatric; Male; Minocycline; Retrospective Studies; Risk Factors; Stenotrophomonas maltophilia; Sulfadoxine; Trimethoprim

The off-label uses of tigecycline (TGC) to treat ventilator-associated pneumonia (VAP) have aroused worldwide concerns. The efficacy about TGC has been recently reported. However, the adverse events (AEs) remain controversial. Our study aims to analyze the safety of the high-dose (HD) regimens in the treatment of VAP due to multidrug-resistant (MDR) pathogens.The clinical data of 134 patients who were diagnosed with VAP from January 2013 to December 2015 in the NeuroScience Care Unit (NCU) were analyzed retrospectively. The incidence and the occurrence time of AEs, 28-day mortality, and the factors of clinical effectiveness were explored.A total of 54 patients received the standard dose group (SD), 69 in the HD, and 11 in the nonstandard HD group (NHD). Acinetobacter baumannii were the main pathogenic bacteria. There was no statistic difference in the incidence of AEs and the 28-day mortality among the 3 groups (P > .05). Total bilirubin (TBIL) increased significantly after SD of TGC treatment (P = .004). Liver dysfunction occurred the latest (10.83 ± 7.08), not in the duration of HD group (9.63 ± 3.92), whereas in the SD group (13.00 ± 7.57) and NHD group (12.64 ± 3.70). Patients with septic shock, MODS, and higher APACHE II score were of high risk in mortality. The HD group was associated with higher clinical effective rate and bacteria clearance rate.HD TGC was relatively safe and tolerable in ICU patients. The risk of side effects was related to the TGC duration, although not increased as the dosage rose. Full course of the HD regimen was associated with better outcomes for the treatment of VAP patients, especially for the MDR gram-negative bacilli infection. Inappropriate antimicrobial treatment might lead to clinical treatment failure.

Topics: Acinetobacter baumannii; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Drug-Related Side Effects and Adverse Reactions; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Minocycline; Pneumonia, Ventilator-Associated; Tigecycline; Treatment Outcome; Young Adult

Cefiderocol (S-649266), a siderophore cephalosporin, utilizes a novel mechanism of entry into the periplasmic space of Gram-negative bacteria and is broadly stable to ESBLs and carbapenemases.. A collection of carbapenem-resistant Gram-negative bacteria isolated from clinical specimens in 18 Greek hospitals was tested for susceptibility to cefiderocol, meropenem, ceftazidime, cefepime, ceftazidime/avibactam, ceftolozane/tazobactam, aztreonam, amikacin, ciprofloxacin, colistin and tigecycline. Broth microdilution plates were used to determine MICs.. In total 189 non-fermentative Gram-negative bacteria (107 Acinetobacter baumannii and 82 Pseudomonas aeruginosa ) and 282 Enterobacteriaceae (including 244 Klebsiella pneumoniae , 14 Enterobacter cloacae and 11 Providencia stuartii ) were studied. For both A. baumannii and P. aeruginosa the MIC 90 of cefiderocol was 0.5 mg/L. For K. pneumoniae , E. cloacae and P. stuartii the MIC 90 of cefiderocol was 1, 1 and 0.5 mg/L, respectively. Tigecycline was the second most active antibiotic, followed by colistin.. Cefiderocol exhibited greater antimicrobial activity in vitro against carbapenem-resistant Gram-negative bacteria than comparator antibiotics.

Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Carbapenems; Cefepime; Cefiderocol; Ceftazidime; Cephalosporins; Colistin; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Greece; Humans; Inpatients; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Minocycline; Pseudomonas aeruginosa; Thienamycins; Tigecycline

The in vitro activity of tigecycline and comparator agents was evaluated against Gram-positive and Gram-negative isolates collected in Latin American centers between 2004 and 2015 as part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) global surveillance study.. Minimum inhibitory concentrations (MICs) were determined using the broth microdilution methodology according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Antimicrobial susceptibility was determined using CLSI breakpoints, except for tigecycline for which the US Food and Drugs Administration breakpoints were used.. This study of isolates from Latin America shows that linezolid, vancomycin and tigecycline continue to be active in vitro against important Gram-positive organisms such as MRSA, and that susceptibility rates to meropenem and tigecycline against members of the Enterobacteriaceae, including ESBL-producers, were high. However, we report that Latin America has high rates of MRSA, MDR A. baumannii and ESBL-producing Enterobacteriaceae which require continued monitoring.

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Epidemiological Monitoring; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Latin America; Microbial Sensitivity Tests; Minocycline; Tigecycline

Trimethoprim-sulfamethoxazole is the first-line antimicrobial combination for Stenotrophomonas maltophilia infections. However, allergy or intolerance and increasing resistance limit the use of trimethoprim-sulfamethoxazole. Quinolones can be used as an alternative therapeutic option, but resistance can emerge rapidly during therapy. We analyzed the contribution of SmeABC and SmeDEF efflux pumps to levofloxacin resistance in clinical isolates of S. maltophilia. Nonduplicate clinical isolates of S. maltophilia were collected in 2010 from 11 university hospitals (n = 102). Fifty-five levofloxacin nonsusceptible (minimum inhibitory concentration [MIC] ≥4 μg/ml) and 47 susceptible (MIC ≤2 μg/ml) isolates were tested for efflux pump overexpression. Real-time reverse transcription-PCR was performed for amplification and quantification of smeB, smeC, smeD, and smeF mRNA. To determine which antimicrobials were affected by smeD overexpression, the growth rates of a levofloxacin-susceptible S. maltophilia isolate were compared by measuring absorbance of antimicrobial-supplemented Luria-Bertani broth (LB) cultures with or without triclosan. Significant relationships between sme gene overexpression and resistance were observed for smeD against levofloxacin, smeC and smeF against ceftazidime, and smeC against ticarcillin-clavulanate. The mean MICs of moxifloxacin and tigecycline did not significantly differ for isolates with or without overexpression of smeB, smeC, and smeF, but were significantly higher for isolates with smeD overexpression. The mean MICs of amikacin were significantly higher for smeC or smeF overexpressing isolates. Increased growth of a levofloxacin-susceptible isolate was observed in LB with 1/2 MIC levofloxacin in the presence of triclosan. These data suggest that the expression of smeD plays a role in levofloxacin resistance in S. maltophilia.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Ceftazidime; Drug Resistance, Multiple, Bacterial; Fluoroquinolones; Gram-Negative Bacterial Infections; Humans; Levofloxacin; Membrane Transport Proteins; Microbial Sensitivity Tests; Minocycline; Moxifloxacin; Stenotrophomonas maltophilia; Ticarcillin; Tigecycline; Trimethoprim, Sulfamethoxazole Drug Combination

The aim of this study was to evaluate the in vitro effects and clinical efficacies of trimethoprim-sulfamethoxazole (SXT) combined with other antimicrobial agents against Stenotrophomonas maltophilia.. In vitro analysis was conducted on 89 S. maltophilia strains isolated from blood and the respiratory tract between June 2012 and October 2014. Levofloxacin (LVX), ticarcillin-clavulanic acid (TIM), and minocycline (MIN) were selected for an examination of their effects when individually combined with SXT by the checkerboard method. In addition, 29 S. maltophilia bacteremia cases were reviewed and the clinical efficacies of SXT-based combination therapies were analyzed.. SXT+LVX showed synergy in 21, no interactions in 61, and antagonism in 7. SXT+TIM showed synergy in 71, and no interactions in 18. SXT+MIN showed synergy in 10, and no interactions in 79. The review of clinical data indicated that a combination of SXT+fluoroquinolone was not associated with improved prognosis compared with monotherapy.. The in vitro data indicated that SXT+TIM had beneficial microbiological effects and was not antagonistic. Our in vitro and clinical data analyses do not support the routine use of SXT+fluoroquinolone combination therapy for S. maltophilia infection.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Clavulanic Acids; Drug Therapy, Combination; Female; Fluoroquinolones; Gram-Negative Bacterial Infections; Humans; Levofloxacin; Male; Middle Aged; Minocycline; Neoplasms; Stenotrophomonas maltophilia; Ticarcillin; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Tigecycline represents one of the last-line therapeutics to combat multidrug-resistant bacterial pathogens, including VRE and MRSA. The German National Reference Centre for Staphylococci and Enterococci has received 73 tigecycline-resistant Enterococcus faecium and Enterococcus faecalis isolates in recent years. The precise mechanism of how enterococci become resistant to tigecycline remains undetermined. This study documents an analysis of the role of efflux pumps in tigecycline resistance in clinical isolates of Enterococcus spp.. Various tigecycline MICs were found for the different isolates analysed. Tigecycline-resistant strains were analysed with respect to genome and transcriptome differences by means of WGS and RT-qPCR. Genes of interest were cloned and expressed in Listeria monocytogenes for verification of their functionality.. Detailed comparative whole-genome analyses of three isogenic strains, showing different levels of tigecycline resistance, revealed the major facilitator superfamily (MFS) efflux pump TetL and the ribosomal protection protein TetM as possible drug resistance proteins. Subsequent RT-qPCR confirmed up-regulation of the respective genes. A correlation of gene copy number and level of MIC was inferred from further qPCR analyses. Expression of both tet(L) and tet(M) in L. monocytogenes unequivocally demonstrated the potential to increase tigecycline MICs upon acquisition of either locus.. Our results indicate that increased expression of two tetracycline resistance determinants, a tet(L)-encoded MFS pump and a tet(M)-encoded ribosomal protection protein, is capable of conferring tigecycline resistance in enterococcal clinical isolates.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Base Sequence; Drug Resistance, Microbial; Enterococcus faecium; Gene Dosage; Gram-Negative Bacterial Infections; Microbial Sensitivity Tests; Minocycline; Plasmids; Polymerase Chain Reaction; Tetracycline Resistance; Tigecycline; Up-Regulation

Stenotrophomonas maltophilia is a Gram-negative bacillus intermittently isolated from hospitalized patients. Trimethoprim/sulfamethoxazole is considered the treatment of choice for S. maltophilia infections, though limited by toxicities. Minocycline is utilized at our institution for S. maltophilia infections due to its improved tolerability and in vitro susceptibility rates. Our objective was to evaluate the effectiveness of minocycline monotherapy compared with trimethoprim/sulfamethoxazole monotherapy for treatment of S. maltophilia infections.. Patients were identified via microbiology laboratory data and those with at least one positive culture for S. maltophilia were cross-referenced with pharmacy data to detect patients who received trimethoprim/sulfamethoxazole or minocycline. Patients initially receiving combination therapy were excluded. Our primary outcome was treatment failure, defined as receipt of alternative antibiotics with in vitro activity against S. maltophilia, isolation of S. maltophilia on repeat culture or death within 30 days of treatment.. Forty-five patients were evaluated. Overall mortality rate was 9% and equal between groups; 41% of patients (9/22) who received trimethoprim/sulfamethoxazole and 30% (7/23) of patients who received minocycline experienced treatment failure (P = 0.67). Patients who received minocycline were more likely to have had a recent acute kidney injury (AKI) (43.5% versus 9%; P = 0.017) or chronic lung disease (52% versus 9%; P = 0.003). Logistic regression showed consistent results of non-inferiority of the primary outcome when controlling for rates of underlying lung pathology and recent AKI (P = 0.728).. Treatment failure did not differ between patients receiving trimethoprim/sulfamethoxazole or minocycline monotherapy for treatment of S. maltophilia infections.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Child; Coinfection; Comorbidity; Female; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Minocycline; Retrospective Studies; Stenotrophomonas maltophilia; Treatment Failure; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Stenotrophomonas maltophilia is an emerging nosocomial pathogen responsible for several infections in immunocompromised patients. To characterize the antimicrobial resistance and virulence potential of this microorganism in a Brazilian hospital, a total of 936 samples were collected from a nosocomial environment and medical devices, and 100 isolates from clinical specimens were obtained in the same hospital. S. maltophilia was found in 3% of the samples collected, especially in bed rails from hospital rooms. The smf-1 gene was detected in 23% and 42% of the clinical and hospital environment isolates, respectively, and almost all (96.8%) isolates that harbored smf-1 were able to form biofilm. All isolates were susceptible to minocycline and chloramphenicol, and the majority of isolates were susceptible to levofloxacin. High resistance to ceftazidime was detected in both groups of isolates. Resistance to trimethoprim-sulfamethoxazole (TMP/SMX) was found in 14.8% of the isolates. All TMP/SMX-resistant isolates presented class 1 integron and sul1 gene, and 47.4% of them also harbored the sul2 gene, which was inserted into a 7.3 kb plasmid. Genetic relatedness among the isolates was evaluated by enterobacterial repetitive intergenic consensus-PCR, and eight genetic patterns were identified. One pattern comprised 54.7% of isolates and was spread among clinical and environmental (furniture and medical devices) sources. The presence of S. maltophilia in the hospital environment indicates that it can act as a reservoir of this microorganism. In addition, hospital isolates resistant to TMP/SMX showed that the genetic determinants were present in mobile elements, which can constitute great concern, as it may indicate a tendency to spread.

Topics: Anti-Bacterial Agents; Bacterial Typing Techniques; Biofilms; Brazil; Ceftazidime; Chloramphenicol; Cross Infection; Drug Resistance, Bacterial; Fomites; Gene Expression Regulation, Bacterial; Genes, Bacterial; Gram-Negative Bacterial Infections; Hospitals; Humans; Integrons; Levofloxacin; Minocycline; Phylogeny; Plasmids; Polymerase Chain Reaction; Stenotrophomonas maltophilia; Trimethoprim, Sulfamethoxazole Drug Combination

Tigecycline has a broad-spectrum in vitro activity against Gram-positive and Gram-negative bacteria, including multidrug-resistant (MDR) strains. However, some Gram-negative bacteria are intrinsically resistant or have reduced susceptibility to tigecycline. We performed a prospective, observational study of 43 patients who received tigecycline as the treatment for serious infections due to MDR Gram-negative microorganisms, to evaluate superinfections. In 60.5% of our patients, tigecycline-resistant (T-R) Gram-negative microorganisms were isolated, representing superinfection in 37.2% and colonization in 23.5%. Pseudomonas aeruginosa was the predominant pathogen (48.4%) followed by Providencia stuartii, Proteus mirabilis and Stenotrophomonas maltophilia. Median time elapsed between tigecycline prescription and isolation of T-R pathogens was 7 days. The 16 superinfections consisted of ventilator-associated pneumonias (43.75%), catheter-related bloodstream infections (37.5%), intra-abdominal infections (12.5%) and urinary tract infection (6.25%). Attributed mortality to superinfections was 31.25%. The comparison of various potential risk factors for isolation of T-R microorganisms did not reveal statistically significant results.

Topics: Aged; Anti-Bacterial Agents; Cross Infection; Drug Resistance, Bacterial; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Minocycline; Risk Factors; Superinfection; Tigecycline

Here we report a case of generalized aggressive periodontitis treated with periodontal therapy including adjunct antimicrobial therapy and periodontal surgery. The patient was a 22-year-old woman who presented with the chief complaint of gingival recession. Baseline examination revealed generalized plaque deposition and gingival inflammation. Thirty-nine percent of the sites had a probing depth (PD) of 4-6 mm and 2% a PD of ≥7 mm; 63% exhibited bleeding on probing (BOP). Radiographic examination revealed vertical bone loss in the molars and horizontal bone loss in other teeth. Microbiological examination of subgingival plaque revealed the presence of Aggregatibacter actinomycetemcomitans and Tannerella forsythia. Oral health-related quality of life was assessed as a measure of patient-reported outcome. Based on a clinical diagnosis of generalized aggressive periodontitis, initial periodontal therapy and adjunct antimicrobial therapy were implemented. After reducing inflammation and subgingival bacteria, open flap debridement was performed for teeth with a PD of ≥4 mm. Reevaluation showed no sites with a PD of ≥5 mm, a minimal level of BOP, and a marked reduction in the level of the targeted periodontal pathogens. The patient's oral health-related quality of life was slightly worsened during supportive periodontal therapy (SPT). Implementation of adjunct antimicrobial therapy targeting periodontal pathogens and subsequent periodontal surgery resulted in improvement in periodontal and microbiological parameters. This improvement has been adequately maintained over a 2-year period. However, additional care is necessary to further improve the patient's oral health-related quality of life during SPT.

Topics: Adult; Aggregatibacter actinomycetemcomitans; Aggressive Periodontitis; Aluminum Compounds; Alveolar Bone Loss; Anti-Bacterial Agents; Chemotherapy, Adjuvant; Cuspid; Dental Enamel Proteins; Dental Plaque; Dental Plaque Index; Dentin Sensitivity; Female; Fluorides; Furcation Defects; Gingival Recession; Gingivitis; Gram-Negative Bacterial Infections; Humans; Malocclusion; Minocycline; Molar; Oral Hygiene; Pasteurellaceae Infections; Patient Care Planning; Periodontal Debridement; Periodontal Index; Periodontal Pocket; Quality of Life; Silicon Compounds; Tannerella forsythia; Tokyo; Treatment Refusal

Topics: Anti-Bacterial Agents; Gram-Negative Bacterial Infections; Humans; Minocycline; Stenotrophomonas maltophilia

The aim of this study was to evaluate the in vitro susceptibility of MDR gram-negatives bacteria to old drugs such as polymyxin B, minocycline and fosfomycin and new drugs such as tigecycline.. One hundred and fifty-three isolates from 4 Brazilian hospitals were evaluated. Forty-seven Acinetobacter baumannii resistant to carbapenens harboring adeB, blaOxA23, blaOxA51, blaOxA143 and blaIMP genes, 48 Stenotrophomonas maltophilia including isolates resistant to levofloxacin and/or trimethoprim-sulfamethoxazole harboring sul-1, sul-2 and qnrMR and 8 Serratia marcescens and 50 Klebsiella pneumoniae resistant to carbapenens harboring blaKPC-2 were tested to determine their minimum inhibitory concentrations (MICs) by microdilution to the following drugs: minocycline, ampicillin-sulbactam, tigecycline, and polymyxin B and by agar dilution to fosfomycin according with breakpoint criteria of CLSI and EUCAST (fosfomycin). In addition, EUCAST fosfomycin breakpoint for Pseudomonas spp. was applied for Acinetobacter spp and S. maltophilia, the FDA criteria for tigecycline was used for Acinetobacter spp and S. maltophilia and the Pseudomonas spp polymyxin B CLSI criterion was used for S. maltophilia.. Tigecycline showed the best in vitro activity against the MDR gram-negative evaluated, followed by polymyxin B and fosfomycin. Polymyxin B resistance among K. pneumoniae was detected in 6 isolates, using the breakpoint of MIC > 8 ug/mL. Two of these isolates were resistant to tigecycline. Minocycline was tested only against S. maltophilia and A. baumannii and showed excellent activity against both.. Fosfomycin seems to not be an option to treat infections due to the A. baumannii and S. maltophilia isolates according with EUCAST breakpoint, on the other hand, showed excellent activity against S. marcescens and K. pneumoniae.

Topics: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Fosfomycin; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Polymyxin B; Tigecycline

The Tigecycline Evaluation and Surveillance Trial (TEST) was designed to monitor susceptibility to commonly used antimicrobial agents among important pathogens. We report here on susceptibility among Gram-negative pathogens collected globally from pediatric patients between 2004 and 2012. Antimicrobial susceptibility was determined using guidelines published by the Clinical and Laboratory Standards Institute (CLSI). Most Enterobacteriaceae showed high rates of susceptibility (>95%) to amikacin, tigecycline, and the carbapenems (imipenem and meropenem); 90.8% of Acinetobacter baumannii isolates were susceptible to minocycline, and susceptibility rates were highest in North America, Europe, and Asia/Pacific Rim. Amikacin was the most active agent against Pseudomonas aeruginosa (90.4% susceptibility), with susceptibility rates being highest in North America. Extended-spectrum β-lactamases (ESBLs) were reported for 11.0% of Escherichia coli isolates and 24.2% of Klebsiella pneumoniae isolates globally, with rates reaching as high as 25.7% in the Middle East and >43% in Africa and Latin America, respectively. Statistically significant (P<0.01) differences in susceptibility rates were noted between pediatric age groups (1 to 5 years, 6 to 12 years, or 13 to 17 years of age), globally and in some regions, for all pathogens except Haemophilus influenzae. Significant (P<0.01) differences were reported for all pathogens globally and in most regions, considerably more frequently, when pediatric and adult susceptibility results were compared. Amikacin, tigecycline, and the carbapenems were active in vitro against most Gram-negative pathogens collected from pediatric patients; A. baumannii and P. aeruginosa were susceptible to fewer antimicrobial agents. Susceptibility rates among isolates from pediatric patients were frequently different from those among isolates collected from adults.

Topics: Adolescent; Anti-Bacterial Agents; Child; Child, Preschool; Drug Resistance, Bacterial; Epidemiological Monitoring; Female; Global Health; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Infant; Male; Microbial Sensitivity Tests; Minocycline; Spatio-Temporal Analysis; Tigecycline

Topics: Anti-Bacterial Agents; Critical Illness; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Male; Minocycline; Severity of Illness Index

Stenotrophomonas maltophilia is an emerging nosocomial pathogen responsible for serious human infections. This study was carried out to determine antibiotic susceptibility, resistance mechanisms (integrons, sul1 and sul2), and genetic relatedness (Enterobacterial Repetitive Intergenic Consensus [ERIC]-PCR) among 106 clinical isolates of S. maltophilia from India. Twenty-four (22.6%) of S. maltophilia isolates exhibited resistance to mainstay antibiotic trimethoprim-sulfamethoxazole (TMP-SMX). Except for 2 isolates which contained both TMP-SMX resistance determinants sul1 and sul2 genes, all other 22 TMP-SMX-resistant isolates carried either sul1 (10 isolates) or sul2 (12 isolates) genes. Class 1 integrons were present in 8.5% (9 out of 106) of S. maltophilia isolates, and only 5 out of these isolates were TMP-SMX resistant and positive for sul1 gene. The same isolates also carried resistance cassettes containing qac/smr gene. Minocycline and levofloxacin exhibited the maximum in vitro activity against S. maltophilia. ERIC-PCR revealed high diversity among S. maltophilia isolates. The present study demonstrated high (22.4%) TMP-SMX resistance in clinical isolates of S. maltophilia from India. TMP-SMX-resistant isolates carried relatively higher percentage of sul2 gene than sul1 gene as against the reported literature. Majority (58.3%) of sul1 gene positive were not associated with class 1 integrase gene.

Topics: Anti-Bacterial Agents; Cross Infection; Drug Resistance, Bacterial; Gram-Negative Bacterial Infections; Humans; India; Integrons; Levofloxacin; Microbial Sensitivity Tests; Minocycline; Molecular Typing; Polymerase Chain Reaction; Stenotrophomonas maltophilia; Tertiary Care Centers; Trimethoprim, Sulfamethoxazole Drug Combination

Stenotrophomonas maltophilia has emerged as an important opportunistic pathogen in recent years. Increasing antimicrobial resistance and other contraindications have greatly compromised trimethoprim/sulfamethoxazole (SXT) as the first-line therapeutic option. The objective of this study was to explore other options for treating hospital-acquired pneumonia (HAP) caused by S. maltophilia.. A total of 102 strains of S. maltophilia were isolated from sputum and bronchoalveolar lavage (BAL) specimens of patients with HAP in our institution. The minimum inhibitory concentration (MIC) values of minocycline, tigecycline, moxifloxacin, and levofloxacin were determined by the agar dilution method. Based on the MICs and the population pharmacokinetic parameters of the investigated antimicrobials, a Monte Carlo simulation was performed to simulate the pharmacokinetic/pharmacodynamic (PK/PD) indices of different regimens. The probability of target attainment (PTA) was estimated at each MIC value and the cumulative fraction of response (CFR) was calculated to evaluate the efficacy of these regimens.. The susceptibility rates to minocycline, tigecycline, moxifloxacin, and levofloxacin were 96.1%, 80.4%, 74.5%, and 69.6%, respectively. The estimated CFRs were 96.2% for minocycline 100 mg twice daily; 50.8%/67.1%/75.4% for tigecycline 50/75/100 mg twice daily; 34.3%/48.0%/56.6% for levofloxacin 500/750/1000 mg once daily; and 45.7% for moxifloxacin 400 mg once daily.. The simulation results suggest that minocycline may be a proper choice for treatment of HAP caused by S. maltophilia, while tigecycline, moxifloxacin, and levofloxacin may not be optimal as monotherapy.

Topics: Adult; Anti-Bacterial Agents; Bronchoalveolar Lavage Fluid; Cross Infection; Female; Fluoroquinolones; Gram-Negative Bacterial Infections; Humans; Levofloxacin; Male; Microbial Sensitivity Tests; Minocycline; Monte Carlo Method; Moxifloxacin; Pneumonia; Sputum; Stenotrophomonas maltophilia; Tigecycline

Sulfamethoxazole-trimethoprim (SXT) is the drug-of-choice in Stenotrophomonas maltophilia caused infections. There has been an increase in resistance to SXT of S. maltophilia over recent years. In this study 30 S. maltophilia clinical isolates resistant to SXT were investigated. Antibiotic susceptibilities for ciprofloxacin, moxifloxacin, levofloxacin, doxycycline, tigecycline, ceftazidime, colistin and chloramphenicol were determined by broth microdilution method. None of the strains were susceptible to ciprofloxacin, tigecycline, ceftazidime or colistin. Only 37% of the isolates were susceptible to levofloxacin or moxifloxacin. Two isolates resistant to all tested antibiotic agents and two others susceptible only to doxycycline were further investigated: susceptibility for combinations of antibiotics was analyzed by checkerboard technique. According to the fractional inhibitory concentration indices calculated, moxifloxacin plus ceftazidime combination was found to be synergistic in each case. Genetic testing revealed the predominance of sul1 gene. Our study concluded that the range of effective antibiotic agents is even more limited in infections caused by SXT-resistant S. maltophilia. In these cases, in vitro synergistic antibiotic combinations could be potential therapeutic options.

Topics: Anti-Bacterial Agents; Ceftazidime; Drug Resistance, Bacterial; Gram-Negative Bacterial Infections; Humans; Hungary; Levofloxacin; Microbial Sensitivity Tests; Minocycline; Stenotrophomonas maltophilia; Tertiary Care Centers; Tigecycline

The Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) was established in 2004 to monitor longitudinal changes in bacterial susceptibility to numerous antimicrobial agents, specifically tigecycline. In this study, susceptibility among Gram-positive and Gram-negative isolates between 2004 and 2011 from the Middle East and Africa was examined. Antimicrobial susceptibilities were determined using Clinical and Laboratory Standards Institute (CLSI) interpretive criteria, and minimum inhibitory concentrations (MICs) were determined by broth microdilution methods. US Food and Drug Administration (FDA)-approved breakpoints were used for tigecycline. In total, 2967 Gram-positive and 6322 Gram-negative isolates were examined from 33 participating centres. All Staphylococcus aureus isolates, including meticillin-resistant S. aureus, were susceptible to tigecycline, linezolid and vancomycin. Vancomycin, linezolid, tigecycline and levofloxacin were highly active (>97.6% susceptibility) against Streptococcus pneumoniae, including penicillin-non-susceptible strains. All Enterococcus faecium isolates were susceptible to tigecycline and linezolid, including 32 vancomycin-resistant isolates. Extended-spectrum β-lactamases were produced by 16.6% of Escherichia coli and 32.9% of Klebsiella pneumoniae. More than 95% of E. coli and Enterobacter spp. were susceptible to amikacin, tigecycline, imipenem and meropenem. The most active agents against Pseudomonas aeruginosa and Acinetobacter baumannii were amikacin (88.0% susceptible) and minocycline (64.2% susceptible), respectively; the MIC90 (MIC required to inhibit 90% of the isolates) of tigecycline against A. baumannii was low at 2mg/L. Tigecycline and carbapenem agents were highly active against most Gram-negative pathogens. Tigecycline, linezolid and vancomycin showed good activity against most Gram-positive pathogens from the Middle East and Africa.

Topics: Africa; Anti-Bacterial Agents; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Middle East; Minocycline; Tigecycline

Bacterial infections because of multidrug-resistant (MDR) bacteria are spreading worldwide. In patients with advanced liver cirrhosis, healthcare-acquired and hospital-acquired infections are common and are frequently sustained by MDR bacteria. In these settings, tigecycline, a new antibiotic, has been shown to be useful in the treatment of MDR bacteria, and it has been proposed for the treatment of hospital-acquired infections in patients with cirrhosis. Nevertheless, poor data exist on the safety profile of tigecycline in patients with cirrhosis. Here, an experience is reported in a female patient with advanced liver cirrhosis, who developed sepsis by an MDR Stenotrophomonas maltophilia and was treated with tigecycline. She experienced life-threatening side effects consisting of severe coagulopathy with hypofibrinogenaemia and subsequent gastrointestinal haemorrhage. The side effect disappeared after the withdrawal of tigecycline. Therefore, a strict monitoring of coagulation parameters in patients with cirrhosis treated with tigecycline is recommended.

Topics: Adult; Afibrinogenemia; Anti-Bacterial Agents; Blood Coagulation Disorders; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Liver Cirrhosis; Minocycline; Opportunistic Infections; Stenotrophomonas maltophilia; Tigecycline

The antimicrobial treatment of Stenotrophomonas maltophilia infections is complicated by intrinsic multidrug resistance and a lack of reliable susceptibility data. We assessed the activity of colistin (COL), rifampicin (RIF) and tigecycline (TGC) alone and in combination using a range of in vitro susceptibility testing methodologies and a simple invertebrate model of S. maltophilia infection (Galleria mellonella). Synergy [fractional inhibitory concentration indices (FICIs) ≤0.5] between COL and either RIF or TGC was observed against 92 % and 88 % of 25 S. maltophilia isolates, respectively, despite resistance to one or another of the single agents alone. In time-kill assays, COL combined with either RIF or TGC was superior to single agents, but only the COL/RIF regimen was reliably bactericidal. The in vitro findings correlated with treatment outcomes in G. mellonella, with heightened survival observed for larvae treated with COL/RIF or COL/TGC compared with COL, RIF or TGC alone. COL combined with RIF was the most effective combination overall in both in vitro and in vivo (p < 0.05) assays. Given the difficulty in selecting appropriate therapy for S. maltophilia infections, regimens consisting of COL combined with RIF or TGC could be considered for clinical use.

Topics: Animals; Colistin; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Gram-Negative Bacterial Infections; Lepidoptera; Microbial Viability; Minocycline; Rifampin; Stenotrophomonas maltophilia; Survival Analysis; Tigecycline; Treatment Outcome

The high incidence of multidrug-resistant (MDR) bacteria among patients admitted to ICUs has determined an increase of tigecycline (TGC) use for the treatment of severe infections. Many concerns have been raised about the efficacy of this molecule and increased dosages have been proposed. Our purpose is to investigate TGC safety and efficacy at higher than standard doses.. We conducted a retrospective study of prospectively collected data in the ICU of a teaching hospital in Rome. Data from all patients treated with TGC for a microbiologically confirmed infection were analyzed. The safety profile and efficacy of high dosing regimen use were investigated.. Over the study period, 54 patients (pts) received TGC at a standard dose (SD group: 50 mg every 12 hours) and 46 at a high dose (HD group: 100 mg every 12 hours). Carbapenem-resistant Acinetobacter.baumannii (blaOXA-58 and blaOXA-23 genes) and Klebsiella pneumoniae (blaKPC-3 gene) were the main isolated pathogens (n = 79). There were no patients requiring TGC discontinuation or dose reduction because of adverse events. In the ventilation-associated pneumonia population (VAP) subgroup (63 patients: 30 received SD and 33 HD), the only independent predictor of clinical cure was the use of high tigecycline dose (odds ratio (OR) 6.25; 95% confidence interval (CI) 1.59 to 24.57; P = 0.009) whilst initial inadequate antimicrobial treatment (IIAT) (OR 0.18; 95% CI 0.05 to 0.68; P = 0.01) and higher Sequential Organ Failure Assessment (SOFA) score (OR 0.66; 95% CI 0.51 to 0.87; P = 0.003) were independently associated with clinical failure.. TGC was well tolerated at a higher than standard dose in a cohort of critically ill patients with severe infections. In the VAP subgroup the high-dose regimen was associated with better outcomes than conventional administration due to Gram-negative MDR bacteria.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Critical Illness; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Prospective Studies; Retrospective Studies; Severity of Illness Index; Tigecycline

Few antimicrobials are currently active to treat infections caused by extremely resistant Gram-negative bacilli (ERGNB), which represent a serious global public health concern. Tigecycline, which covers the majority of these ERGNB (with the exception of Pseudomonas aeruginosa), is not currently approved for hospital-acquired pneumonia, and several meta-analyses have suggested an increased risk of death in patients receiving this antibiotic. Other studies suggest that the use of high-dose tigecycline may represent an alternative in daily practice. De Pascale and colleagues report that the clinical cure rate in patients with ventilator-associated pneumonia is significantly higher with a high dose of tigecycline than with the conventional dose, although mortality was unaffected. This high dose is safe; no patients required discontinuation or dose reduction.

Topics: Anti-Bacterial Agents; Critical Illness; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Male; Minocycline; Severity of Illness Index

In intensive care units (ICUs), the most important causes of nosocomial bacterial infections are mainly multidrug-resistant (MDR) and extensively drug-resistant (XDR) Acinetobacter baumannii and Klebsiella pneumoniae strains. Mortality related to these infections is very high due to lack of effective therapy and the severity of patient conditions. This study aimed to assess the prevalence of carbapenem resistance genes in 77 carbapenem-resistant Gram-negative bacteria isolated from severe infections (bloodstream, pulmonary and urinary tract) during the period 1 January to 31 July 2013 in a general ICU in Catania, Italy, and to examine their susceptibility to tigecycline and colistin using two different methods. In total, 52 A. baumannii belonging to the same sequence type (ST) 2 clone and carrying the bla(OXA-23) gene as well as 25 K. pneumoniae carrying bla(KPC-3) were isolated. Four distinct pulsotypes were identified in K. pneumoniae, which correlated with four distinct STs: ST258 and ST512, spread worldwide, and ST147 and ST395 detected for the first time in Italy. A. baumannii isolates showed an XDR profile and were fully susceptible only to colistin; all KPC-producing K. pneumoniae isolates were MDR, whilst colistin was active against 19 of 25 strains. These results show that broth microdilution (BMD) is a reliable in vitro susceptibility test for colistin, above all K. pneumoniae, whilst both the gradient test and BMD are suitable for tigecycline susceptibility testing of A. baumannii.

Topics: Acinetobacter baumannii; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Genotype; Gram-Negative Bacterial Infections; Humans; Intensive Care Units; Italy; Klebsiella pneumoniae; Microbial Sensitivity Tests; Minocycline; Multilocus Sequence Typing; Tigecycline

Topics: Female; Gram-Negative Bacterial Infections; Humans; Middle Aged; Minocycline; Stenotrophomonas maltophilia; Tigecycline

For an antibacterial agent to be considered for clinical studies in nosocomial pneumonia (NP), it should be active in the presence of pulmonary surfactant. Furthermore, owing to the common practice of treating such infections with more than one antibacterial agent, it should be free of antagonistic interactions with agents of other classes. The aim of this study was to demonstrate the effect of pulmonary surfactant on the activity of ceftazidime and ceftazidime-avibactam and to determine the interaction (if any) of ceftazidime-avibactam and six antimicrobial agents common in the treatment of NP. Minimum inhibitory concentration (MIC) determination for ceftazidime and ceftazidime-avibactam was performed with and without the presence of four concentrations of bovine pulmonary surfactant, and a chequerboard assay was used to determine any interaction between ceftazidime and ceftazidime-avibactam with tobramycin, levofloxacin, linezolid, vancomycin, tigecycline and colistin. Here we report that the in vitro antimicrobial activity of ceftazidime-avibactam against β-lactamase-producing Gram-negative bacteria remained unaltered in the presence of pulmonary surfactant at concentrations that antagonised the antimicrobial activity of daptomycin. Furthermore, in chequerboard interaction studies, an absence of antagonism was demonstrated between ceftazidime-avibactam and six antimicrobial agents of different classes when tested against aerobic species frequently isolated from NP. The results support the further investigation of ceftazidime-avibactam as a potential treatment for NP caused by susceptible bacteria.

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; beta-Lactamases; Ceftazidime; Cross Infection; Drug Therapy, Combination; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Pneumonia, Bacterial; Pulmonary Surfactants; Tigecycline; Tobramycin

In the era of carbapenem-resistance in Acinobacter baumannii and Enterobacteriaceae, there are limited treatment options for these pathogens. It is essential that clinicians fully assess all available therapeutic alternatives for these multidrug-resistant organisms. We herein describe the approach of the antimicrobial stewardship team at the Detroit Medical Center (DMC) for the evaluation and use of intravenous (IV) minocycline for the treatment of these resistant organisms, given potential advantages of IV minocycline over tigecycline and doxycycline. In vitro analyses at the DMC demonstrated good activity against A. baumannii (78% susceptibility), including 74% of carbapenem-resistant strains, but limited activity against our carbapenem-resistant K.pneumoniae (12% susceptibility.) Based in part on these results, IV minocycline was added to the formulary, primarily for the treatment of carbapenem-resistant A. baumannii. Early experience has been positive: 6/9 (67%) of patients who received IV minocycline had infections due to these organisms cured, including 6/7 (86%) who received doses of 200 mg twice daily.

Topics: Administration, Intravenous; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Carbapenems; Drug Resistance, Bacterial; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Male; Michigan; Middle Aged; Minocycline; Pharmacy Service, Hospital

Intra-abdominal infection (IAI) is a frequent complication found in surgical intensive care unit (SICU) and continues to be associated with considerable mortality. Tigecycline, the first-in-class glycylcycline has demonstrated a broad spectrum of activity against a wide range of bacteria commonly found in IAI. This observational retrospective study aimed to describe the experience with tigecycline for serious nosocomial IAI in the SICU. Data were collected from 23 consecutive patients admitted to SICU with serious nococomial IAI who had received empirical treatment with tigecycline. In all cases, IAI was diagnosed via emergency surgery. Severe sepsis was found in 56.5% and 43.5% developed septic shock. Oncological disease was the most common comorbidity (60%). The mean Simplified Acute Physiology Score (SAPS) III within 24 hours from IAI diagnosis was 57.5±14.7, and 87% showed a McCabe score >1 (2 or 3). Escherichia coli was the most common pathogen (43.5%), followed by Bacteroides spp. and Streptococcus spp. (30.4%, respectively). All but one patient received tigecycline in combination (95.7%), particularly with fluconazole (52.2%), followed by piperacillin-tazobactam (43.5%). Empirical antibiotic therapy was considered adequate in 95%. The mean duration of treatment was 8.5±4.5 days. A favorable response was achieved in 78%. Failure of the antibiotic therapy was not observed in any patient. None of the patients discontinued tigecycline due to adverse reactions. SICU mortality was 13%, with no deaths attributable to tigecycline. These findings suggest that tigecycline combination therapy is an effective and well tolerated empirical treatment of serious nosocomial IAI in the SICU.

Topics: Adult; Aged; Anti-Bacterial Agents; Combined Modality Therapy; Comorbidity; Critical Care; Critical Illness; Cross Infection; Drug Evaluation; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Hospital Mortality; Humans; Male; Middle Aged; Minocycline; Neoplasms; Postoperative Complications; Retrospective Studies; Sepsis; Shock, Septic; Tigecycline; Treatment Outcome

The Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) commenced in 2004 to longitudinally monitor global changes in bacterial susceptibility to a suite of antimicrobial agents. The current study examined the activity of tigecycline and comparators against isolates collected across Eastern Europe between 2004 and 2010. Minimum inhibitory concentrations were determined using Clinical and Laboratory Standards Institute (CLSI) broth microdilution methodologies. Antimicrobial susceptibility was determined using CLSI interpretive criteria, and tigecycline susceptibility was established using European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints. This study included 10 295 Gram-negative and 4611 Gram-positive isolates from 42 centres. Extended-spectrum β-lactamases (ESBLs) were reported among 15.3% of Escherichia coli and 39.3% of Klebsiella pneumoniae isolates; the highest rates were observed in Turkey (30.9%) and Bulgaria (53.8%), respectively. Imipenem-non-susceptible K. pneumoniae were identified only in Turkey. ESBL-positive E. coli were highly susceptible to imipenem (95.1%), meropenem (98.0%) and tigecycline (98.5%). Most antimicrobials showed poor activity against Acinetobacter baumannii and Pseudomonas aeruginosa. Vancomycin resistance was noted among 0.9% of Enterococcus faecalis and 11.7% of Enterococcus faecium isolates. High rates of susceptibility were reported for linezolid (99.7%) and tigecycline (100%) against E. faecium. One-quarter of Staphylococcus aureus isolates were meticillin-resistant S. aureus (MRSA), with the highest rate in Romania (51.5%); all MRSA were susceptible to linezolid, tigecycline and vancomycin. Antimicrobial resistance is high in much of Eastern Europe, with considerable variation seen among countries. Tigecycline and the carbapenems retain excellent activity against many pathogens from Eastern Europe; linezolid and vancomycin are active against most Gram-positive pathogens.

Topics: Anti-Bacterial Agents; Europe, Eastern; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Longitudinal Studies; Microbial Sensitivity Tests; Minocycline; Tigecycline

A Stenotrophomonas maltophilia mutant that coordinately hyper-expresses three resistance nodulation division-type efflux pump genes, smeZ, smeJ, and smeK, has been identified. SmeZ is responsible for elevating aminoglycoside MICs; SmeJ and SmeK are jointly responsible for elevating tetracycline, minocycline, and ciprofloxacin MICs and conferring levofloxacin resistance. One clinical isolate with this same phenotype was identified from a sample of six, and the isolate also coordinately hyper-expresses smeZ and smeJK, confirming the clinical relevance of our findings.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Bacterial Toxins; Ciprofloxacin; Gene Expression; Genes, MDR; Gram-Negative Bacterial Infections; Humans; Levofloxacin; Membrane Transport Proteins; Microbial Sensitivity Tests; Minocycline; Ofloxacin; Stenotrophomonas maltophilia; Tetracycline

The aim of this study was to determine antimicrobial susceptibility of recent clinical Stenotrophomonas maltophilia isolates from Korea, and to compare the activity levels of several combinations of antimicrobials. A total of 206 non-duplicate clinical isolates of S. maltophilia was collected in 2010 from 11 university hospitals. Antimicrobial susceptibility testing was performed using the Clinical Laboratory Standards Institute agar dilution method. In vitro activity of antimicrobial combinations was tested using the checkerboard method. The susceptibility rates to trimethoprim-sulfamethoxazole and minocycline were 96% and 99%, respectively. The susceptibility rate to levofloxacin was 64%. All of four antimicrobial combinations showed synergy against many S. maltophilia isolates. A combination of trimethoprim-sulfamethoxazole plus ticarcillin-clavulanate was most synergistic among the combinations. None of the combinations showed antagonistic activity. Therefore, some of the combinations may be more useful than individual drugs in the treatment of S. maltophilia infection. Further clinical studies are warranted to validate our in vitro test results.

Topics: Anti-Infective Agents; Gram-Negative Bacterial Infections; Hospitals, University; Humans; Levofloxacin; Microbial Sensitivity Tests; Minocycline; Ofloxacin; Republic of Korea; Stenotrophomonas maltophilia; Trimethoprim, Sulfamethoxazole Drug Combination

The Tigecycline Evaluation and Surveillance Trial is an antimicrobial susceptibility surveillance program that collects gram-positive and gram-negative organisms globally.. This analysis reports on antimicrobial susceptibility among 23,918 gram-negative isolates collected from intensive care units globally between 2004 and 2009.. MICs and susceptibility were determined according to the guidelines of the Clinical and Laboratory Standards Institute (US Food and Drug Administration breakpoints were applied against tigecycline).. Gram-negative isolates were collected from 6 geographical regions: North America, 8099 isolates; Europe, 9244; Asia-Pacific Rim, 1573; Latin America, 3996; the Middle East, 635; and Africa, 371. North America reported the lowest rates of extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae and Escherichia coli both overall (12.8% and 4.7%, respectively) and in each year of collection. High rates of ESBL production were reported among K pneumoniae from Latin America (45.5%) and Africa (54.9%) and for E coli from the Middle East (32.4%). Imipenem and tigecycline maintained >90% susceptibility against K pneumoniae, E coli, Klebsiella oxytoca, Enterobacter cloacae, and Serratia marcescens for all regions. Susceptibility to meropenem was >90% against all K oxytoca and S marcescens. Large regional variations in susceptibility among Acinetobacter baumannii were reported, with the largest variations reported for amikacin (75.2% in North America, 21.8% in the Middle East) and meropenem (60.4% in North America, 15.9% in Africa). MIC(90) values for tigecycline against A baumannii were low (1-2 mg/L) for all regions. Against P aeruginosa, susceptibility to amikacin (97.5% in North America, 67.5% in Latin America) and meropenem (79.1% in North America, 51.4% in Africa) had the largest variations.. Antimicrobial resistance among gram-negative intensive care unit isolates was highly variable between geographic regions. The carbapenems were active in vitro against Enterobacteriaceae, A baumannii and P aeruginosa, and tigecycline continued to be active in vitro against members of the Enterobacteriaceae and A baumannii collected from intensive care units in North America, Europe, the Asia-Pacific Rim, Latin America, the Middle East, and Africa.

Topics: Adolescent; Adult; Africa; Aged; Anti-Infective Agents; Asia; Drug Resistance, Bacterial; Europe; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Intensive Care Units; Latin America; Male; Microbial Sensitivity Tests; Middle Aged; Middle East; Minocycline; North America; Tigecycline; Time Factors; Young Adult

Here we report on the antimicrobial resistance amongst Gram-negative isolates (excluding Acinetobacter spp.) collected from blood culture sources at European study sites as part of the global Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) from the study start in 2004 until August 2009. All isolates were collected and tested for minimum inhibitory concentrations using Clinical and Laboratory Standards Institute methodology. Over the collection period, extended-spectrum β-lactamase (ESBL) production was recorded in 21.1% of Klebsiella pneumoniae, 2.6% of Klebsiella oxytoca and 11.3% of Escherichia coli, primarily in Croatia, Greece, Hungary, Italy, Poland, Romania and the Slovak Republic. ESBL rates stabilised amongst K. pneumoniae over 2006-2009, but doubled amongst E. coli in 2008-2009. The patterns of antimicrobial resistance changed accordingly for both organisms. Generally, Greece had the highest antimicrobial resistance for K. pneumoniae, Italy for E. coli, Serratia marcescens and Enterobacter spp., and Croatia for Pseudomonas aeruginosa. High resistance rates amongst K. pneumoniae were also seen in Croatia and Italy. Imipenem resistance amongst K. pneumoniae was reported exclusively in Greece (13.8%); amongst other Enterobacteriaceae, imipenem resistance was absent or low. Similarly, meropenem resistance was low amongst the Enterobacteriaceae except K. pneumoniae from Greece (42.6%). Across Europe, the most active antimicrobial agents against the Enterobacteriaceae were tigecycline, amikacin and the carbapenems, each with <10% resistance each year. Against the other antimicrobials, significant increases in non-susceptibility were reported for K. pneumoniae and E. coli, both important causative pathogens of bacteraemia.

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Blood; Europe; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

Topics: Anti-Bacterial Agents; Bacteremia; Blood; Critical Illness; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; India; Microbial Sensitivity Tests; Minocycline; Tigecycline

Topics: Adult; Aged; Anti-Bacterial Agents; Carrier State; Clinical Trials as Topic; Cross Infection; Female; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Minocycline; Off-Label Use; Opportunistic Infections; Practice Guidelines as Topic; Salvage Therapy; Soft Tissue Infections; Stenotrophomonas maltophilia; Tigecycline

In this prospective multicentric study, we assessed the in vitro antimicrobial activity of carbapenems (imipenem, meropenem, and doripenem), tigecycline, and colistin against 166 unusual nonfermenting Gram-negative bacilli (NF-GNB) clinical isolates collected from nine French hospitals during a 6-month period (from December 1, 2008, to May 31, 2009). All NF-GNB isolates were included, except those phenotypically identified as Pseudomonas aeruginosa or Acinetobacter baumannii. Minimal inhibitory concentrations (MICs) of antimicrobial agents were determined by using the E-test technique. The following microorganisms were identified: Stenotrophomonas maltophilia (n=72), Pseudomonas spp. (n=30), Achromobacter xylosoxidans (n=25), Acinetobacter spp. (n=18), Burkholderia cepacia complex (n=9), Alcaligenes faecalis (n=7), and Delftia spp. (n=5). All isolates of Acinetobacter spp., A. faecalis, and Delftia spp. were susceptible to the three carbapenems. Imipenem exhibited the lowest MICs against Pseudomonas spp., and meropenem, as compared with imipenem and doripenem, displayed an interesting antimicrobial activity against A. xylosoxidans and B. cepacia complex isolates. Conversely, no carbapenem exhibited any activity against S. maltophilia. Except for S. maltophilia isolates, tigecycline and colistin exhibited higher MICs than carbapenems, but covered most of the microorganisms tested in this study. To our knowledge, no prior study has compared antimicrobial activity of these five antibiotics, often considered as "last-resort" treatment options for resistant Gram-negative infections, against unusual NF-GNB clinical isolates. Further studies should be carried out to assess the potential clinical use of these antibiotics for the treatment of infections due to these microorganisms.

Topics: Anti-Bacterial Agents; Bacterial Typing Techniques; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

A total of 10948 clinical isolates was collected throughout the Asia-Pacific region as part of the Tigecycline Evaluation Surveillance Trial (TEST) during 2004-2010, consisting of 7549 Gram-negative and 3399 Gram-positive pathogens. Susceptibility trends for all species demonstrated several significant species-dependent susceptibility changes to multiple antibiotics. The most notable was minocycline, for which significant decreases in susceptibility (P<0.001) were observed for six of the ten species studied. In contrast, statistically significant susceptibility changes for tigecycline were observed in only two of the ten species, namely Klebsiella pneumoniae and Serratia marcescens. Seven years following the introduction of tigecycline into clinical use, this agent remains highly active against a wide range of pathogens from the Asia-Pacific region.

Topics: Anti-Bacterial Agents; Asia; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Population Surveillance; Species Specificity; Tigecycline

Trimethoprim-sulfamethoxazole (TMP-SMZ) is recommended as the treatment of choice for Stenotrophomonas maltophilia infections. However, when the administration of TMP-SMZ is not possible, alternative treatment options for S. maltophilia infections has not been clearly established. We compare the efficacy of tigecycline treatment with TMP-SMZ in nosocomial S. maltophilia infections during a 3-year period. For the treatment of S. maltophilia infection, 26 (57.8%) patients received TMP-SMZ and 19 (42.2%) patients received tigecycline. Culture positivity rate was 95.7% in TMP-SMZ group and 70.6% in tigecycline group at the seventh day (P = 0.028), whereas 26.3% versus 18.8% at the fourteenth day (P = 0.700). Clinical improvement was observed 69.2% in TMP-SMZ group and 68.4% in tigecycline group at the fourteenth day (P = 0.954). Mortality rates at the thirtieth day were respectively, 30.8 and 21.1% in TMP-SMZ and tigecycline groups (P = 0.517). There were no significant differences in mortality and clinical response rates between TMP-SMZ and tigecycline treatment. Tigecycline can be considered as an alternative option beyond TMP-SMZ in treatment of S. maltophilia infections.

Topics: Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Drug Therapy, Combination; Female; Gram-Negative Bacterial Infections; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Prognosis; Retrospective Studies; Stenotrophomonas maltophilia; Survival Rate; Tigecycline; Trimethoprim, Sulfamethoxazole Drug Combination

Criteria of tigecycline (Tygacil) use for the treatment of surgical site infections in oncologic inpatients were developed. High efficacy of tigecycline in vitro and in vivo against multiresistant hospital strains persistent in the surgical department of the gastrointestinal oncologic division was shown.

Topics: Aged; Anti-Bacterial Agents; Cross Infection; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Neoplasms; Surgical Wound Infection; Tigecycline

To document the development of resistance to tigecycline in comparison with 17 other antimicrobials, the susceptibilities of 2,741 isolates comprising 16 bacterial species recovered from hospitalised patients in 15 German centres in 2009 were assessed. The results were compared with those of previous trials (German Tigecycline Evaluation Surveillance Trial, G-TEST I and II, performed in 2005 and 2007, respectively) conducted prior to and shortly after the introduction of tigecycline in Germany. Moreover, the in vitro activities of tigecycline against the subset of multidrug-resistant (MDR) pathogens recovered within all three sampling periods (n = 4,988) were evaluated in comparison to the corresponding non-MDR isolates. All susceptibility tests were performed by broth microdilution. Between 2005 and 2009, tigecycline retained its high activity against Gram-positive and Gram-negative organisms, including MDR pathogens. By contrast, an in part marked increase in resistance to broad-spectrum beta-lactams and fluoroquinolones was observed for many Enterobacteriaceae and for non-fermenting Gram-negative bacteria. Against a background of a steadily increasing number of multiresistant pathogens, the activity of tigecycline remained unaltered. With the exception of Acinetobacter isolates with decreased susceptibility to carbapenems, tigecycline's activity profile was not notably affected by organisms resistant to other drug classes and, thus, holds promise as an important therapeutic agent, particularly for situations in which MDR organisms are suspected.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Child; Child, Preschool; Drug Resistance, Multiple, Bacterial; Female; Germany; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Infant; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Tigecycline; Young Adult

Although polymicrobial infections, such as peri-implantitis or periodontitis, were postulated in the literature to be caused by synergistic effects of bacteria, these effects remain unclear looking at antibiotic susceptibility. The aim of this study is to compare the antibiotic susceptibilities of pure cultures and definite cocultures.. Laboratory strains of Aggregatibacter actinomycetemcomitans (Aa) (previously Actinobacillus actinomycetemcomitans), Capnocytophaga ochracea (Co), and Parvimonas micra (Pm) (previously Peptostreptococcus micros) were cultivated under anaerobic conditions, and their susceptibilities to 10 antibiotics (benzylpenicillin G, ampicillin, amoxicillin, ampicillin/sulbactam, amoxicillin/clavulanic acid, minocycline, metronidazole, linezolid, azithromycin, and moxifloxacin) were tested using the Epsilometertest. Cocultures, each consisting of two or three bacteria, were treated analogously.. All four cocultures showed lower susceptibilities to azithromycin and minocycline than to pure cultures. The coculture Aa-Co showed a lower susceptibility to moxifloxacin as did the coculture Aa-Pm to benzylpenicillin G; the coculture Co-Pm showed a lower susceptibility to amoxicillin, amoxicillin/clavulanic acid, metronidazole, and benzylpenicillin G. However, the coculture Co-Pm showed a higher susceptibility to ampicillin, linezolid and moxifloxacin as did Aa-Pm and Aa-Co-Pm to linezolid.. In addition to established in vitro assays, it was demonstrated that antimicrobial cocultures caused antibiotic susceptibilities that differed from those of pure cultures. Bacterial cocultures frequently showed lowered susceptibilities to antibiotics.

Topics: Acetamides; Actinobacillus Infections; Aggregatibacter actinomycetemcomitans; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Ampicillin; Anti-Bacterial Agents; Anti-Infective Agents; Aza Compounds; Azithromycin; Capnocytophaga; Coculture Techniques; Coinfection; Drug Resistance, Bacterial; Fluoroquinolones; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Linezolid; Metronidazole; Microbial Interactions; Minocycline; Moxifloxacin; Oxazolidinones; Penicillin G; Peptostreptococcus; Peri-Implantitis; Periodontitis; Quinolines; Sulbactam

Topics: Anti-Bacterial Agents; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

The emergence of infections caused by multidrug-resistant Gram-negative bacteria, in particular Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae, has necessitated the search for alternative therapy by either introducing new agents or renewing interest in old agents. This study compares the in vitro activity of tigecycline (TIG), recently introduced to Egyptian market, to other potentially active antimicrobials as Colistin (COL), imipenem (IPM), levofloxacin (LEV), and piperacillin/tazobactam (PIP/TAZ) against 67 Gram-negative clinical isolates obtained from El- Meery Hospital in Alexandria, Egypt. El-Meery Hospital is a 1,500-bed tertiary teaching hospital where TIG has not been previously used. Based on MIC(90)s, TIG was found to be a comparator to IPM and COL (MIC(90)= 8 μg/ml). LEV and PIP/TAZ were less active than TIG exhibiting high MIC(90)s. TIG inhibited 100% of Escherichia coli and K. pneumoniae and 60% of Ps. aeruginosa and A. baumannii isolates. In time-kill studies against IPM-resistant isolates, TIG showed bactericidal activity after 6 hours of contact against the Enterobacteriaceae isolates and after 3 hours for the tested Ps. aeruginosa isolates at 4× and 8× MIC. Against A. baumannii, TIG exerted a bacteriostatic effect. TIG demonstrated variable ability to suppress biofilm formation affecting mainly E. coli and A. baumannii isolates. These results point TIG to be a promising agent in treatment of infections caused by strains for which adequate therapy has been limited. As far as we know, this is the first report evaluating the in vitro activity of TIG against Egyptian clinical isolates.

Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Biofilms; Drug Resistance, Multiple, Bacterial; Egypt; Escherichia coli; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Hospitals, Teaching; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

Activity of tigecycline against nosocomial secondary peritonitis isolates collected along 18 months in 29 Spanish hospitals was tested by Etest in a central laboratory, considering Food and Drug Administration (FDA)/British Society for Antimicrobial Chemotherapy (BSAC)/European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints. A total of 600 facultative/aerobic isolates (392 Gram negative, 208 Gram positive) and 100 anaerobes were tested. None of the 220 Escherichia coli isolates was resistant to tigecycline (MIC(50)/MIC(90) = 0.25/0.5 microg/mL), with 0.5% (FDA breakpoint) and 3.6% (BSAC/EUCAST breakpoint) intermediate strains. All Extended-spectrum beta-lactamase (ESBL)-producing E. coli isolates (15 strains), all Klebsiella pneumoniae, and Klebsiella oxytoca isolates (42 strains) were susceptible to tigecycline. No isolates resistant to tigecycline were found among Streptococcus viridans, Staphylococcus aureus, and Enterococcus faecium, but 18.9% of Enterococcus faecalis strains were intermediate following BSAC/EUCAST breakpoints. All (but 1) isolates of the Bacteroides fragilis group (n = 45) were tigecycline susceptible, as well as Gram-positive anaerobes. Tigecycline offers an adequate activity profile against isolates from secondary peritonitis when tested by Etest regardless of the breakpoints used for categorization.

Topics: Anti-Bacterial Agents; Bacteria, Anaerobic; Cohort Studies; Cross Infection; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Peritonitis; Tigecycline

To determine the in vitro activity of tigecycline and comparator common use antimicrobial agents tested against contemporary bacterial pathogens from the Asia-Western Pacific region.. As part of the SENTRY Antimicrobial Surveillance Program, a total of 5759 Gram-positive and Gram-negative isolates were collected from 28 medical centers in eight Asia-Western Pacific countries during 2008. Minimum inhibitory concentrations (MICs) were determined using Clinical and Laboratory Standards Institute (CLSI) broth microdilution method and interpreted using CLSI breakpoints. United States Food and Drug Administration (US-FDA) breakpoints were used to interpret tigecycline susceptibility.. Antimicrobial resistance was found to be widespread and prevalence varied considerably between the eight countries. Against pathogens for which breakpoints were available, >98% of all isolates were susceptible to tigecycline. Against all Gram-positive isolates, including methicillin (oxacillin)-resistant Staphylococcus aureus, penicillin- and multidrug-resistant pneumococci, and vancomycin-resistant enterococci, the highest tigecycline MIC found was 1 microg/ml. Against all Enterobacteriaceae, including extended-spectrum beta-lactamase phenotypes, tigecycline susceptibility was 97.5%. Tigecycline had good activity against Acinetobacter spp. but was much less active against Pseudomonas aeruginosa.. Tigecycline demonstrated excellent sustained in vitro activity against a wide spectrum of contemporary Gram-positive and -negative pathogens from Asia-Western Pacific countries.

Topics: Anti-Bacterial Agents; Asia, Eastern; Asia, Southeastern; Australia; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; New Zealand; Sentinel Surveillance; Tigecycline

Antimicrobial susceptibilities were determined for 1,586 isolates of Stenotrophomonas maltophilia from globally diverse medical centers using the Clinical Laboratory Standards Institute broth microdilution method. The combination trimethoprim-sulfamethoxazole (96.0% of isolates susceptible at < or =2 microg/ml trimethoprim and 38 microg/ml sulfamethoxazole) and tigecycline (95.5% of isolates sussceptible at < or =2 microg/ml) were the only antimicrobials tested with >94% susceptibility in all regions. Susceptibility rates for other commonly used were lower than expected and varied geographically. This in vitro data supports tigecycline as a potential candidate for clinical investigations into S. maltophilia infections.

Topics: Anti-Bacterial Agents; Asia; Europe; Gram-Negative Bacterial Infections; Humans; In Vitro Techniques; Latin America; Microbial Sensitivity Tests; Minocycline; North America; Stenotrophomonas maltophilia; Tigecycline

A multicentre surveillance of tigecycline activity against relevant pathogens in the UK.. Forty-three representative UK hospitals were each asked to test 150 consecutive, clinically significant isolates from hospitalized patients, excluding those from urine or faeces. The sentinel laboratories tested all these isolates against a panel of antibiotics by the BSAC disc method and a selection of isolates were retested centrally by the BSAC agar dilution method.. The isolates collected comprised Staphylococcus aureus (39.9%), Escherichia coli (13.3%), streptococci (11.9%), enterococci (6.3%), Klebsiella (6.1%), coagulase-negative staphylococci (6.1%), Enterobacter spp. (3.9%), Proteus spp. (2.2%) and other Gram-negative species (10.3%). The laboratories' disc susceptibility testing found that 4% of isolates were resistant to tigecycline, using the zone breakpoints in place at that time. However, centralized retesting by agar dilution showed that many of these 'resistant' isolates were susceptible, with resistance only confirmed in a range of Gram-negative isolates and one S. aureus. These findings reduced the estimated resistance rate to 2.4%, or to 0.8% if Proteus spp. were ignored as intrinsically resistant to tigecycline. Sixty-two percent of the isolates found resistant by the disc method but susceptible by agar dilution had zones of inhibition within experimental error (4 mm) of the published breakpoints.. Tigecycline resistance was rare in isolates causing clinically significant infections in the UK and was overestimated ∼2-fold by the BSAC disc method. Adjustment of the breakpoints might overcome this problem but at the risk of increasing the false susceptibility rate. The best advice is to perform dilution tests, e.g. by gradient strip test on isolates with borderline results, especially in severe infection and when tigecycline use is intended.

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; False Negative Reactions; False Positive Reactions; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Sentinel Surveillance; Tigecycline; United Kingdom

As part of the Tigecycline Evaluation and Surveillance Trial (TEST), Gram-negative and Gram-positive organisms were collected from 31 medical centres in nine countries in the Asia-Pacific Rim between 2004 and 2007. Overall, 34.2% of Acinetobacter spp. were multidrug-resistant, and 17.0% of Klebsiella pneumoniae and 10.6% of Escherichia coli produced extended-spectrum beta-lactamases. A total of 39.5% of Staphylococcus aureus were meticillin-resistant and 21.7% of Enterococcus faecium were vancomycin-resistant. Tigecycline MIC(90) values (minimum inhibitory concentration for 90% of the organisms) were

Topics: Anti-Bacterial Agents; Asia; beta-Lactamases; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Male; Methicillin Resistance; Microbial Sensitivity Tests; Minocycline; Oceania; Tigecycline; Vancomycin Resistance

Tigecycline is a broad-spectrum antimicrobial agent that has been approved for the treatment of skin and soft-tissue infections as well as intra-abdominal infections. The Tigecycline Evaluation and Surveillance Trial (TEST) is a global, longitudinal surveillance study established in 2004 to monitor the in vitro activity of tigecycline and comparator agents against key Gram-negative and Gram-positive pathogens. This report examines data obtained for 24748 isolates collected across 24 European countries between 2004 and 2007. Tigecycline, meropenem and imipenem were the most active antimicrobial agents against most Gram-negative isolates including multidrug-resistant Acinetobacter baumannii (15.7% of the A. baumannii isolates in this study), extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (8.5% of E. coli) and ESBL-producing Klebsiella pneumoniae (13.6% of K. pneumoniae). Only amikacin was active against >90% of Pseudomonas aeruginosa isolates (92.8% susceptible). Tigecycline, linezolid and vancomycin were the most active agents against Gram-positive agents across Europe between 2004 and 2007, with tigecycline displaying the lowest MIC(90) values (minimum inhibitory concentration for 90% of the organisms) against meticillin-resistant Staphylococcus aureus (26.5% of the collected S. aureus isolates), vancomycin-resistant Enterococcus faecium (15.7% of the E. faecium strains) and penicillin-resistant Streptococcus pneumoniae (9.3% of the S. pneumoniae strains). Longitudinal analysis showed no increase in tigecycline MIC values over the 4-year study period, whilst increased resistance was noted for several comparator agents.

Topics: Anti-Bacterial Agents; Europe; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Longitudinal Studies; Microbial Sensitivity Tests; Minocycline; Tigecycline

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

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

In the last years, the increase of antibiotic resistances of gram-positive and gram-negative bacteria is an important therapeutic problem. The antimicrobial activity of tigecycline, a novel glycylcycline, was evaluated against 750 bacterial isolates from 30 centers in Spain.. Multicenter and retrospective study. In 2005, thirty laboratories participated in this study. Data collected in this study included antimicrobial susceptibilities for S.aureus resistant to methicillin (MRSA), ESBL- E. coli or ESBL- K. pneumoniae, E. coli resistant to quinolons (E.coli- QR), Klebsiella spp and E. faecalis. Trains were obtained of the each Hospital s collection (5 strains of each microorganisms). The susceptibility determinations were performed locally by each laboratory following the standard method usually performed. The tigecycline susceptibility determinations were performed with E/test.. Tigecycline was the most potent agent against MRSA, E. faecalis, E.coli-QR and ESBLs enterobacteriaceae; with MIC50-MIC90 values of: 0.125-0.25 g/ml; 0.125-0.5 g/ml; 0.25-0.75 g/ml and 0.38-1.5 g/ml; respectively.. The results of this study confirm the excellent in vitro activity of tigecycline against gram-positive and gram-negative pathogens, including multirresistant microorganisms.

Topics: Anti-Bacterial Agents; Drug Evaluation, Preclinical; Drug Resistance, Multiple, Bacterial; Enterococcus faecalis; Escherichia coli; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; In Vitro Techniques; Klebsiella; Laboratories, Hospital; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minocycline; Retrospective Studies; Spain; Tigecycline

Topics: Adolescent; Anti-Bacterial Agents; Gram-Negative Bacterial Infections; Humans; Male; Minocycline; Soft Tissue Infections; Stenotrophomonas maltophilia; Tigecycline

The lack of data from the Middle East warranted studying tigecycline in vitro activity in Lebanon against consecutive multidrug-resistant (MDR) bacteria, including extended-spectrum beta-lactamases producing clinical isolates of Escherichia coli (n = 150), Klebsiella pneumoniae (n = 100), and Acinetobacter spp. (n = 64) using the standard disk diffusion method. Tigecycline-resistant and intermediate findings were as follows: E. coli, 0% and 0%; K. pneumoniae, 3% and 16%; and Acinetobacter spp., 0% and 2%. These values were substantially lower than those determined for amikacin, gentamicin, tobramycin, ciprofloxacin, piperacillin/tazobactam, amoxicillin/clavulanic acid, and trimethoprim/sulfamethoxazole. This study demonstrates the excellent activity of tigecycline against the increasingly encountered MDR bacteria in Lebanon. The introduction of this effective and viable drug for the initial or recommended treatment of serious infections caused by such highly resistant pathogens is an asset for patients in this country and elsewhere.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Child; Child, Preschool; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Infant; Lebanon; Middle Aged; Minocycline; Tigecycline

Elizabethkingia miricola is a Gram-negative rod that was initially isolated from condensation water of the space station Mir. This is the 1st reported case of human disease caused by this organism.

Topics: Anti-Bacterial Agents; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Levofloxacin; Lymphoma, Mantle-Cell; Male; Middle Aged; Minocycline; Ofloxacin; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Sepsis; Stem Cell Transplantation; Tigecycline

Topics: Aged; Anti-Bacterial Agents; Carcinoma, Transitional Cell; Cross Infection; Drug Resistance, Multiple; Emphysema; Gram-Negative Bacterial Infections; Humans; Lupus Erythematosus, Discoid; Male; Minocycline; Obesity; Pneumonia, Bacterial; Pulmonary Disease, Chronic Obstructive; Stenotrophomonas maltophilia; Tigecycline; Urinary Bladder Neoplasms

In this study (part of the global TEST program), the in vitro activity of tigecycline, a member of a new class of antimicrobial agents, the glycylcyclines, against clinical isolates collected in Italy was evaluated.. A total of 200 clinical isolates were collected and identified in our institution during 2005. Minimum inhibitory concentrations (MICs) of the antimicrobial agents were determined by the broth microdilution method recommended by the CLSI in 2005.. Globally, 135 Gram-negative and 65 Gram-positive pathogens were evaluated. Tigecycline demonstrated excellent inhibitory activity against Acinetobacter spp., Haemophilus influenzae, Escherichia coli, Enterococcus spp., Staphylococcus aureus, Streptococcus agalactiae and Streptococcus pneumoniae with MIC(90)

Topics: Anti-Bacterial Agents; Community-Acquired Infections; Cross Infection; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Italy; Microbial Sensitivity Tests; Minocycline; Tigecycline

Dentists generally recognize the importance of periodontal treatment in patients with leukemia, with the most attention paid to preventing the development of odontogenic infection. For physicians, the worst type of infection is one caused by multidrug-resistant bacteria. Here, we report a patient with an abnormal increase in multidrug-resistant opportunistic bacteria in the gingiva during hematopoietic cell transplantation (HCT).. A 53-year-old woman receiving HCT for leukemia had an insufficient blood cell count for invasive periodontal treatment before HCT. Even brushing caused difficulties with hemostasis. Therefore, frequent pocket irrigation and local minocycline administration were performed.. The multidrug-resistant opportunistic bacterium Stenotrophomonas maltophilia was detected first in phlegm 2 days before HCT, and it was detected in a gingival smear and a blood sample 7 and 11 days after HCT, respectively. The patient developed sepsis on day 11 and died 14 days after HCT. Frequent irrigation and local antibiotic application were ineffective against S. maltophilia on the gingiva. Inflammatory gingiva without scaling and root planing showed bleeding tendency, and this interfered with the eradication of this bacterium.. The gingiva in patients undergoing leukemia treatment acts as sites of proliferation and reservoirs for multidrug-resistant opportunistic bacteria. Severe systemic infection by multidrug-resistant bacteria in such patients with leukemia also may involve the gingiva. To prevent abnormal increases in such bacteria on the gingiva, scaling and/or root planing before chemotherapy, which reduces bleeding on brushing during the neutropenic period caused by chemotherapy, may contribute to infection control in such patients, although it was impossible in this case.

Topics: Anti-Bacterial Agents; Anti-Infective Agents, Local; Drug Resistance, Multiple, Bacterial; Fatal Outcome; Female; Gingival Diseases; Gingivitis; Gram-Negative Bacterial Infections; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Middle Aged; Minocycline; Opportunistic Infections; Periodontitis; Povidone-Iodine; Sepsis; Stenotrophomonas maltophilia; Transplantation Conditioning; Whole-Body Irradiation

Eighteen patients received tigecycline as treatment for infection due to multidrug-resistant gram-negative bacilli, including Acinetobacter baumannii and Klebsiella pneumoniae carbapenemase- and extended-spectrum beta-lactamase-producing Enterobacteriaceae. Pretherapy minimum inhibitory concentration values for tigecycline predicted clinical success. Observed evolution of resistance during therapy raises concern about routine use of tigecycline in treatment of such infections when other therapies are available.

Topics: Acinetobacter baumannii; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamases; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Tigecycline; Treatment Outcome

As part of the tigecycline evaluation and surveillance trial (TEST), bacterial isolates were collected from 39 centres in France, Germany, Italy, Spain and the UK between January 2004 and August 2006. Antimicrobial susceptibilities were determined according to CLSI guidelines. Italy had the highest rate of methicillin-resistant Staphylococcus aureus (36.4%), and was the only country to report vancomycin-resistant Enterococcus faecalis (8.6%). Tigecycline was the only agent to which all Gram-positive isolates were susceptible. For many of the Gram-negative organisms collected, antimicrobial susceptibilities were lowest among isolates from Italy and highest among isolates from Spain. The notable exception was Acinetobacter baumannii, where the poorest susceptibility profile was among isolates from Spain. For A. baumannii, MIC(90)s of imipenem varied from 1 mg/L for isolates in France and Germany to > or =32 mg/L for isolates from Italy and Spain. Tigecycline was the only agent to maintain an MIC(90) of < or =1 mg/L against isolates from all five countries. The in-vitro activity of tigecycline against both Gram-positive and Gram-negative isolates may make it valuable in the treatment of hospital infections, including those caused by otherwise antimicrobial-resistant organisms.

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Europe; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Gram-Positive Cocci; Humans; Microbial Sensitivity Tests; Minocycline; Population Surveillance; Tigecycline

In clinical trials tigecycline was similar to vancomycin/aztreonam for complicated skin and skin structure infections, but data comparing it with other widely used antibiotics are lacking. We predicted the pharmacodynamic cumulative fraction of response (CFR) of tigecycline against bacteria implicated in complicated skin and skin structure infections and compared it with the CFRs for piperacillin/tazobactam, ceftriaxone, levofloxacin, and imipenem/cilastatin.. A 5,000-patient Monte Carlo simulation using a two-compartment intravenous infusion model was used to simulate steady-state concentrations for common dosages of these antibiotics. Population pharmacokinetics data from infected patients were employed. The CFR was calculated against Staphylococcus aureus (42% methicillin-resistant S. aureus [MRSA]), streptococci, coagulase-negative staphylococci, Escherichia coli, Enterobacter, enterococci, Proteus mirabilis, Klebsiella, and Pseudomonas aeruginosa collected from worldwide surveillance (TEST and SENTRY) and weighted by prevalence of involvement in complicated skin and skin structure infections.. Excluding MRSA, the weighted CFR was greatest for imipenem/cilastatin and piperacillin/tazobactam regimens (93.9%-95.9%). With 42% MRSA added to the model, only tigecycline monotherapy achieved a high CFR (88.2%). The addition of vancomycin raised the CFR to 91.0%, 89.5%, 88.3%, 82.9%, and 78% for imipenem/cilastatin 500 mg q6h, imipenem/cilastatin 500 mg q8h, piperacillin/tazobactam, levofloxacin, and ceftriaxone regimens, respectively.. Tigecycline monotherapy had a likelihood of achieving its requisite pharmacodynamic exposure similar to that of combinations of piperacillin/tazobactam or imipenem/cilastatin plus vancomycin for the empiric treatment of complicated skin and skin structure infections.

Topics: Anti-Bacterial Agents; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Minocycline; Models, Statistical; Monte Carlo Method; Skin Diseases, Bacterial; Tigecycline

All 198 Salmonella isolates (58.6% of isolates were resistant to tetracycline), 92 Vibrio isolates (4.4% of isolates were resistant to tetracycline), and 200 of 201 Aeromonas isolates (39.3% of isolates were resistant to tetracycline; 1 A. caviae isolate had a tigecycline MIC of 4 mug/ml) in our study were susceptible to tigecycline, by U. S. Food and Drug Administration criteria for Enterobacteriaceae.

Topics: Aeromonas; Anti-Bacterial Agents; Gram-Negative Bacterial Infections; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Minocycline; Salmonella; Salmonella Infections; Taiwan; Tetracycline Resistance; Tigecycline; Vibrio; Vibrio Infections

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

The in vitro activities of tigecycline and selected antimicrobials were evaluated against a variety of multiple-drug-resistant clinical isolates, including extended-spectrum beta-lactamase- and/or metallo-beta-lactamase-producing gram-negative strains, colistin-resistant strains, vancomycin- and/or linezolid-resistant enterococci, and methicillin-resistant Staphylococcus aureus (MRSA). Tigecycline showed excellent activity against a collection of difficult-to-treat pathogens currently encountered in the hospital setting.

Topics: Anti-Bacterial Agents; Cross Infection; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Greece; Humans; Minocycline; Tigecycline

The antimicrobial activity of tigecycline, a novel glycylcycline, was evaluated against 1102 bacterial isolates from 20 centers in Spain. The MIC of tigecycline at which 90% (MIC(90)) of the pneumococci tested were inhibited was the lowest (0.06 microg/mL) of all the antibiotics tested. The MICs of tigecycline against enterococci ranged from 0.03 to 0.125 microg/mL. All staphylococci were inhibited by < or =0.25 microg/mL of tigecycline, and 99.6% of Enterobacteriaceae isolates were inhibited by < or =2 microg/mL of tigecycline. Tigecycline demonstrated good activity against Bacteroides fragilis group organisms with an MIC(90) of 4 microg/mL. The results of this study confirm the excellent activity of tigecycline against multiresistant Gram-positive and Gram-negative pathogens.

Topics: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Sentinel Surveillance; Spain; Tigecycline

Tigecycline is the first glycylcycline antimicrobial in phase III clinical trials. This study compares the in vitro activity of tigecycline to 12 other predominately broad-spectrum antimicrobials against 3049 recent inpatient isolates from 38 clinical centers in 17 countries. The minimum concentration at which tigecycline inhibited 90% of the isolates for the entire collection, excluding Pseudomonas aeruginosa, was 1 microg/mL, including vancomycin-resistant enterococci-, extended-spectrum beta-lactamase-, and methicillin-resistant Staphylococcus aureus-resistant phenotypes.

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Europe; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Middle East; Minocycline; South Africa; Tigecycline

The Tigecycline Evaluation and Surveillance Trial (TEST Program) determined the in vitro activity of tigecycline over a large population of organisms from geographically diverse sites. Tigecycline was compared to amikacin, ampicillin, amoxicillin/clavulanic acid, imipenem, cefepime, ceftazidime, ceftriaxone, levofloxacin, minocycline, piperacillin/tazobactam, linezolid, penicillin, and vancomycin against 3989 commonly encountered clinical Gram-negative and Gram-positive pathogens collected from sites in the United States during 2004. The tigecycline activity was equivalent to imipenem against Enterobacteriaceae. Tigecycline inhibited extended-spectrum beta-lactamase and AmpC phenotypes at MIC90 values (minimum inhibitory concentration) of < or =2 microg/mL. In vitro results for tigecycline were similar to other broad-spectrum antimicrobial agents against nonfermenters with MIC90 results of 2 microg/mL against Acinetobacter spp. and >16 microg/mL against Pseudomonas aeruginosa. Tigecycline demonstrated potent activity against Staphylococcus aureus (MIC90, 0.25 microg/mL) and enterococci (MIC90, 0.12 microg/mL) regardless of methicillin or vancomycin susceptibility. Tigecycline MIC values were unaffected by penicillin nonsusceptibility and beta-lactamase production among fastidious respiratory pathogens (Streptococcus pneumoniae [MIC90, 0.5 microg/mL] and Haemophilus influenzae [MIC90, 0.25 microg/mL]). Tigecycline offers excellent activity against most of the commonly encountered nosocomial and community-acquired bacterial pathogens.

Topics: Anti-Bacterial Agents; Community-Acquired Infections; Cross Infection; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

The activity of tigecycline (formerly GAR936), a novel glycylcycline, was tested against recent bloodstream infection (BSI) pathogen isolates from 6 continents. Frequency of clinical occurrence of these pathogens was determined and their antibiograms assessed using reference broth microdilution methods. A total of 26474 strains were tested for tigecycline susceptibility according to the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards) by the M7-A6 guidelines with interpretations from M100-S15 and the package insert. The rank order of pathogens was Staphylococcus aureus (33.1%), Escherichia coli (14.0%), coagulase-negative staphylococci (13.5%), Enterococcus spp. (12.3%), Klebsiella spp. (5.7%), Pseudomonas aeruginosa (4.2%), Enterobacter spp. (3.0%), beta-hemolytic streptococci (2.9%), Streptococcus pneumoniae (2.3%), and viridans group streptococci (1.4%). Tigecycline exhibited a broader spectrum of activity against BSI isolates when compared to ciprofloxacin, tetracycline, aminoglycosides, and many beta-lactams (imipenem). Tigecycline was highly active against most pathogens tested, including staphylococci (MIC(90), 0.5 microg/mL), enterococci (MIC90, 0.25 microg/mL), streptococci (MIC(90), < or =0.12 microg/mL), Escherichia coli (MIC90, 0.25 microg/mL), Klebsiella spp. (MIC90, 1 mmicrog/mL), and Enterobacter spp. (MIC(90), 2 mmicrog/mL), but showed limited inhibition of Pseudomonas aeruginosa (MIC90, 16 microg/mL) and indole-positive or indole-negative Proteae (MIC90, 4-8 microg/mL). In summary, tigecycline exhibited a wide spectrum of antimicrobial potency versus BSI isolates collected worldwide. Serious infections in nosocomial environments should benefit from tigecycline use among the investigational phase 3 agents focused toward resistant strains.

Topics: Anti-Bacterial Agents; Bacteremia; Cross Infection; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

The antimicrobial activity of tigecycline, a novel glycylcycline, was evaluated against 5289 bacterial isolates recovered from hospitalized patients with skin and soft tissue infections during 2000-2004. Strains were submitted from >70 medical centers in North America, Latin America, and Europe, and were tested centrally using reference broth microdilution methods. The top 10 ranking pathogens (95% of total) recovered included Staphylococcus aureus (55.2%), Enterococcus spp. (9.6%), Pseudomonas aeruginosa (6.4%), Escherichia coli (5.6%), beta-hemolytic streptococci (5.0%), coagulase-negative staphylococci (4.9%), Enterobacter spp. (2.8%), Klebsiella spp. (2.6%), Proteus mirabilis (1.7%), and indole-positive Proteae (1.2%). All staphylococci (S. aureus and coagulase-negative staphylococci), enterococci, beta-hemolytic streptococci, viridans group streptococci, and E. coli were inhibited by < or =2 microg/mL of tigecycline; in addition, 97% of Klebsiella spp., 95% of Enterobacter spp., and 97% of Acinetobacter spp. were inhibited at this concentration. Only P. aeruginosa and all Proteae (MIC90, 16 microg/mL) displayed elevated MIC values to tigecycline. The broad spectrum of activity exhibited by this glycylcycline included tetracycline-resistant organism subsets, as well as oxacillin-resistant S. aureus, vancomycin-resistant enterococci, and extended-spectrum beta-lactamase-producing enteric bacilli strains. Tigecycline represents a new choice among broad-spectrum parenteral agents for the common Gram-positive and -negative pathogens producing serious infections of skin and soft tissues.

Topics: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Skin Diseases, Bacterial; Soft Tissue Infections; Tigecycline

The antimicrobial activity of tigecycline and selected antimicrobials was evaluated against bacterial pathogens isolated from patients hospitalized in intensive care units (ICUs) worldwide. A total of 9093 isolates were consecutively collected in >70 medical centers in North America (4157), South America (1830), Europe (3034), and the Asia-Australia (72) areas. The isolates were collected from the bloodstream (68.5%), respiratory tract (13.6%), skin/soft tissue (5.5%), and urinary tract (2.0%) infections in the 2000-2004 period, and susceptibility was tested by reference broth microdilution methods. The most frequently isolated pathogens were Staphylococcus aureus (32.1%), Enterococcus spp. (13.7%), coagulase-negative staphylococci (CoNS; 13.0%), Pseudomonas aeruginosa (8.4%), and Escherichia coli (7.9%). All Gram-positive pathogens (5665) were inhibited at < or =1 microg/mL of tigecycline. Resistance to oxacillin was detected in 43.5% of Staphylococcus aureus and in 85.0% of CoNS, and resistance to vancomycin was observed in 18.6% of enterococci. Tigecycline was very active against Enterobacteriaceae (1876 strains tested) with an MIC90 of < or =1 microg/mL, except for Serratia spp. (2 microg/mL). Extended-spectrum beta-lactamase (ESBL) phenotype was detected in 10% of E. coli and 31% of Klebsiella spp., whereas 28% of Enterobacter spp. were resistant to ceftazidime (AmpC enzyme production). These resistance phenotypes did not adversely affect tigecycline activity. Tigecycline and trimethoprim/sulfamethoxazole were the most active compounds against Stenotrophomonas maltophilia (MIC90, 2 and 1 microg/mL respectively). Tigecycline was also active against Acinetobacter spp. (MIC90, 1 microg/mL), but P. aeruginosa showed decreased susceptibility to tigecycline (MIC90, 16 microg/mL). In summary, isolates from ICU patients worldwide showed high rates of antimicrobial resistance. The most alarming problems detected were vancomycin resistance among enterococci, ESBL-mediated beta-lactam resistance and fluoroquinolone resistance among Enterobacteriaceae, and carbapenem resistance among P. aeruginosa and Acinetobacter spp. Tigecycline exhibited potent in vitro activity against most of clinically important pathogenic bacteria (except P. aeruginosa) isolated from ICU patients and may represent an excellent option for the treatment of infections in this clinical environment.

Topics: Anti-Bacterial Agents; Cross Infection; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Intensive Care Units; Microbial Sensitivity Tests; Minocycline; Tigecycline

Tigecycline, a new glycylcycline antibiotic, has shown promising in vitro activity against many common pathogens, including multidrug-resistant strains. To determine the activity of tigecycline against a broad range of pathogens from diverse populations and geographic areas, the Tigecycline Evaluation and Surveillance Trial (TEST Program) commenced in 2003. This study evaluated the activity of tigecycline and commonly used antimicrobials against 6792 clinical isolates from 40 study centers in 11 countries. Tigecycline was the most active agent tested against Gram-positive facultative species including multidrug-resistant strains. MIC90 results (microg/mL) for tigecycline against Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, Streptococcus agalactiae, and Streptococcus pneumoniae were 0.12, 0.12, 0.25, and 0.25 microg/mL, respectively. Tigecycline was active against Enterobacteriaceae with an MIC90 of 1 microg/mL. Haemophilus influenzae was very susceptible to tigecycline with an MIC90 of only 0.25 microg/mL. Pseudomonas aeruginosa was the least susceptible organism tested against tigecycline. Tigecycline appears to be a promising new glycylcycline agent for the treatment of many types of pathogens with varying resistance phenotypes.

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

In determining the quality control limits for the Clinical Laboratory Standards Institute-recommended quality control organisms with tigecycline, a number of inconsistencies in the results were encountered that appeared to be related to the age of the Mueller-Hinton broth II. This study was performed to examine the effect of medium age and supplementation with Oxyrase on the activity of tigecycline using a large number of clinical isolates.

Topics: Catalysis; Culture Media; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Microbial Sensitivity Tests; Minocycline; Oxidation-Reduction; Oxygen; Oxygenases; Tigecycline

A total of 7,566 unique patient isolates of Haemophilus influenzae and 2,314 unique patient isolates of Moraxella catarrhalis were collected between October 1997 and June 2002 from 25 medical centers in 9 of the 10 Canadian provinces. Among the 7,566 H. influenzae isolates, 22.5% produced beta-lactamase, while 92.4% of the 2,314 M. catarrhalis isolates produced beta-lactamase. The incidence of beta-lactamase-producing H. influenzae isolates decreased significantly over the 5-year study period, from 24.2% in 1997-1998 to 18.6% in 2001-2002 (P < 0.01). The incidence of beta-lactamase-producing M. catarrhalis isolates did not change over the study period. The overall rates of resistance to amoxicillin and amoxicillin-clavulanate for H. influenzae were 19.3 and 0.1%, respectively. The rank order of cephalosporin activity based on the MICs at which 90% of isolates were inhibited (MIC(90)s) was cefotaxime > cefixime > cefuroxime > cefprozil > cefaclor. On the basis of the MICs, azithromycin was more active than clarithromycin (14-OH clarithromycin was not tested); however, on the basis of the NCCLS breakpoints, resistance rates were 2.1 and 1.6%, respectively. Rates of resistance to other agents were as follows: doxycycline, 1.5%; trimethoprim-sulfamethoxazole, 14.2%; and chloramphenicol, 0.2%. All fluoroquinolones tested, including the investigational fluoroquinolones BMS284756 (garenoxacin) and ABT-492, displayed potent activities against H. influenzae, with MIC(90)s of < or = 0.03 microg/ml. The MIC(90)s of the investigational ketolides telithromycin and ABT-773 were 2 and 4 microg/ml, respectively, and the MIC(90) of the investigational glycylcycline GAR-936 (tigecycline) was 4 microg/ml. Among the M. catarrhalis isolates tested, the resistance rates derived by using the NCCLS breakpoint criteria for H. influenzae were <1% for all antibiotics tested except trimethoprim-sulfamethoxazole (1.5%). In summary, the incidence of beta-lactamase-positive H. influenzae strains in Canada is decreasing (18.6% in 2001-2002), while the incidence of beta-lactamase-positive M. catarrhalis strains has remained constant (90.0% in 2001-2002).

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Canada; Drug Resistance, Multiple, Bacterial; Erythromycin; Female; Gram-Negative Bacterial Infections; Haemophilus influenzae; Humans; Influenza, Human; Ketolides; Longitudinal Studies; Macrolides; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Moraxella catarrhalis; Respiratory Tract Infections; Tigecycline

Aeromonas hydrophila, an uncommon human pathogen, can cause invasive infections in immunocompromised individuals. As the fluoroquinolones have been shown to be active in vitro against mesophilic aeromonads and clinical experience with the use of fluoroquinolones to treat aeromonads infections is limited, the antimicrobial activities of five selected drugs (ciprofloxacin, gatifloxacin, levofloxacin, lomefloxacin, and moxifloxacin) against A. hydrophila were studied in vitro and in mice. The MICs of the fluoroquinolones (except lomefloxacin), cefotaxime, and minocycline for 90% of 64 clinical isolates of A. hydrophila tested by the agar dilution method were

Topics: Aeromonas hydrophila; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Aza Compounds; Cefotaxime; Ciprofloxacin; Fluoroquinolones; Gatifloxacin; Gram-Negative Bacterial Infections; Humans; In Vitro Techniques; Levofloxacin; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Minocycline; Moxifloxacin; Ofloxacin; Quinolines; Quinolones

The activity of tigecycline was compared with those of other antimicrobials against 90 isolates of Eikenella corrodens. The MIC at which 90% of the isolates were inhibited was 2 micro g/ml for tigecycline and 1,

Topics: Anti-Bacterial Agents; Eikenella corrodens; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

The incidence of beta-lactamase production in anaerobic gram-negative rods isolated from 93 pus specimens of orofacial odontogenic infections and the antimicrobial susceptibility of these isolates against 11 antibiotics were determined. A total of 191 anaerobic gram-negative rods were isolated from the specimens. Beta-lactamase was detected in 35.6% of the black-pigmented Prevotella and 31.9% of the nonpigmented Prevotella. However, no strains among the other species isolated produced beta-lactamase. Ampicillin, cefazolin and cefotaxime showed decreased activity as regards beta-lactamase-positive Prevotella strains, whereas the activity of ampicillin/sulbactam, cefmetazole, and imipenem continued to be effective against such strains. All tested beta-lactam antibiotics were effective against Porphyromonas and Fusobacterium. Erythromycin showed decreased activity against nonpigmented Prevotella and Fusobacterium. Clindamycin, minocycline and metronidazole were powerful antibiotics against which anaerobic gram-negative rods could be tested. The present study showed that beta-lactamase-positive strains were found more frequently in the Prevotella strains than in any of the other species of anaerobic gram-negative rods. The effectiveness of adding sulbactam to ampicillin was demonstrated, as well as the difference in cephalosporin activity against beta-lactamase-positive strains.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ampicillin Resistance; Anti-Bacterial Agents; Bacteroidaceae Infections; beta-Lactam Resistance; beta-Lactamases; Cefmetazole; Cephalosporin Resistance; Cephamycins; Chi-Square Distribution; Clindamycin; Erythromycin; Fusobacterium; Gram-Negative Anaerobic Straight, Curved, and Helical Rods; Gram-Negative Bacterial Infections; Humans; Imipenem; Metronidazole; Middle Aged; Minocycline; Periodontal Diseases; Porphyromonas; Prevotella; Sulbactam; Thienamycins; Tooth Diseases

The activities of cefotaxime and minocycline against Aeromonas hydrophila were investigated. Cefotaxime (4 times the MIC) plus minocycline (0.75 times the MIC) elicited an inhibitory effect for 48 h in a time-kill study, and more infected mice treated with both drugs survived (91%) than survived after treatment with cefotaxime (9%) or minocycline (44%) alone, suggesting that cefotaxime and minocycline act synergistically against A. hydrophila.

Topics: Aeromonas hydrophila; Animals; Anti-Bacterial Agents; Cefotaxime; Cephalosporins; Drug Synergism; Drug Therapy, Combination; Gram-Negative Bacterial Infections; Kinetics; Mice; Microbial Sensitivity Tests; Minocycline; Survival Analysis

Our objective was to determine the in vitro activity of minocycline against isolates of Burkholderia cepacia (BC), Stenotrophomonas maltophilia (SM), and Pseudomonas aeruginosa (PA) cultured from the respiratory tract of patients with cystic fibrosis (CF). Cultures of BC, SM, and PA were isolated in a hospital bacteriology laboratory from the sputum or oropharyngeal cultures obtained from patients attending a Cystic Fibrosis Center, and were prospectively tested for in vitro sensitivity to minocycline by Kirby-Bauer disk diffusion. From January 1994 to July 1995, 116 cultures from 61 patients had at least one of the three pathogens; 9/61 (15%) patients had an isolate of BC, and 7/9 (78%) had an initial isolate sensitive to minocycline, of which 3 were sensitive only to minocycline; 2 cultures were resistant to all antibiotics. Four of 7 patients with BC were treated with minocycline; 3 patients developed resistant isolates 3-13 months after therapy. Five of 61 patients (8%) had an isolate of SM: 4/5 (80%) of these isolates were sensitive to minocycline, of which 1 was sensitive only to minocycline. Fifty-five of 61 patients (90%) had at least one PA isolate, with 112 morphotypes recovered from 90 cultures: 40/112 morphotypes (36%) were sensitive to minocycline, 65 (58%) were resistant, and 7 (6%) were intermediate in sensitivity. We conclude that the marked in vitro activity of minocycline against BC and SM isolated from patients with CF suggests that minocycline may have an adjunct role in the antimicrobial therapy of multidrug resistant, respiratory pathogens in CF.

Topics: Adolescent; Anti-Bacterial Agents; Burkholderia cepacia; Burkholderia Infections; Child; Child, Preschool; Cystic Fibrosis; Drug Resistance, Multiple; Female; Gram-Negative Bacterial Infections; Humans; Male; Minocycline; Oropharynx; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections; Sputum; Stenotrophomonas maltophilia; Tetracycline Resistance

The in vivo pharmacodynamic activities of two glycylcyclines (GAR-936 and WAY 152,288) were assessed in an experimental murine thigh infection model in neutropenic mice. Mice were infected with one of several strains of Streptococcus pneumoniae, Staphylococcus aureus, Escherichia coli, or Klebsiella pneumoniae. Most infections were treated with a twice-daily dosing schedule, with administration of 0.75 to 192 mg of GAR-936 or WAY 152,288 per kg of body weight. A maximum-effect dose-response model was used to calculate the dose that produced a net bacteriostatic effect over 24 h of therapy. This dose was called the bacteriostatic dose. More extensive dosing studies were performed with S. pneumoniae 1199, E. coli ATCC 25922, and K. pneumoniae ATCC 43816, with doses being given as one, two, four, or eight equal doses over a period of 24 h. The dosing schedules were designed in order to minimize the interrelationship between the various pharmacokinetic and pharmacodynamic parameters studied. These parameters were time above 0.03 to 32 times the MIC, area under the concentration-time curve (AUC), and maximum concentration of drug in serum (C(max)). The bacteriostatic dose remained essentially the same, irrespective of the dosing frequency, for S. pneumoniae 1199 (0.3 to 0.9 mg/kg/day). For E. coli ATCC 25922 and K. pneumoniae ATCC 43816, however, more frequent dosing led to lower bacteriostatic doses. Pharmacokinetic studies demonstrated dose-dependent elimination half-lives of 1.05 to 2.34 and 1.65 to 3.36 h and serum protein bindings of 59 and 71% for GAR-936 and WAY 152,288, respectively. GAR-936 and WAY 152,288 were similarly effective against the microorganisms studied, with small differences in maximum effect and 50% effective dose. The glycylcyclines were also similarly effective against tetracycline-sensitive and tetracycline-resistant bacteria. Time above a certain factor (range, 0.5 to 4 times) of the MIC was a better predictor of in vivo efficacy than C(max) or AUC for most organism-drug combinations. The results demonstrate that in order to achieve 80% maximum efficacy, the concentration of unbound drug in serum should be maintained above the MIC for at least 50% of the time for GAR-936 and for at least 75% of the time for WAY 152,288. The results of these experiments will aid in the rational design of dose-finding studies for these glycylcyclines in humans.

Topics: Animals; Anti-Bacterial Agents; Area Under Curve; Colony Count, Microbial; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Half-Life; Mice; Mice, Inbred ICR; Minocycline; Muscle, Skeletal; Neutropenia; Survival Analysis; Tigecycline

A 49-year-old man, who had a 3-year history of liver dysfunction but had not been treated, was admitted to the hospital with a sudden onset of fever and generalized muscle pain. He subsequently developed generalized purpura with scattered hemorrhagic bullae of the skin and massive bloody stools. Aeromonas sobria was proven by culture of both blood and bullous fluid. In spite of the extensive treatment with antibiotics and other medications in the intensive care unit (ICU), the patient went into septic shock and died 2 days after admission. Pathological examination on autopsy revealed segmental necrotizing gastroenteritis with bacterial colonies and alcoholic liver cirrhosis, in addition to extensive severe soft tissue damage involving cellulitis and rhabdomyolysis and epidermolysis. Although the prognosis for Vibrio vulnificus infection with severe soft tissue damage in patients with liver cirrhosis, malignancy, diabetes mellitus or other pre-existing diseases is poor, the unfavorable progression of Aeromonas species, especially A. sobria infection is rare. This is thought to be the first report of an autopsied case.

Topics: Aeromonas; Dopamine; Enterocolitis, Necrotizing; Fatal Outcome; Gastroenteritis; Gram-Negative Bacterial Infections; Humans; Imipenem; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Minocycline; Multiple Organ Failure; Norepinephrine; Shock, Septic; Soft Tissue Infections