colistin and Bacteremia

To evaluate whether intravenous colistin in combination with other antibiotics (IVCC) is associated with lower mortality compared with intravenous colistin monotherapy (IVCM), and to identify factors influencing study outcomes.. PubMed and Scopus were searched up to November 2016. Studies were included if they evaluated adult patients with multi-drug-resistant (MDR) or extensively-drug-resistant Gram-negative infections, and reported comparative mortality data (adjusted and unadjusted) for patients receiving IVCC vs. IVCM. Random effects meta-analyses were performed.. Thirty-two studies (29 observational, three randomized) were included. The overall quality of data was low to very low, and studies were characterized by the lack of adjusted data. The majority of studies were not designed to evaluate the outcome of the meta-analysis, and focused mainly on infections due to Acinetobacter baumannii and Klebsiella pneumoniae. Colistin was administered at variable doses, with or without a loading dose, and in combination with several antibiotics. Overall, IVCC was not associated with lower mortality than IVCM [32 studies, 2328 patients, risk ratio (RR) 0.91, 95% confidence interval (CI) 0.81-1.02, I. Overall, low-quality data suggest that IVCC did not lower mortality in patients with MDR Gram-negative infections. However, there is some evidence for a benefit observed with high intravenous doses of colistin.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Intravenous; Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Klebsiella Infections; Klebsiella pneumoniae

The spread of carbapenemase-producing K. pneumoniae (CPKP) has become a significant problem worldwide. Combination therapy for CPKP is encouraging, but polymyxin resistance to many antibiotics is hampering effective treatment. Combination therapy with three or more antibiotics is being increasingly reported, therefore we performed a systematic review of triple combination cases in an effort to evaluate their clinical effectiveness for CPKP infections.. The PubMed database was searched to identify all published clinical outcomes of CPKP infections treated with triple combination therapy. Articles were stratified into two tiers depending on the level of clinical detail provided. A tier 1 study included: antibiotic regimen, regimen-specific outcome, patient status at onset of infection, and source of infection. Articles not reaching these criteria were considered tier 2.. Thirty-three studies were eligible, 23 tier 1 and ten tier 2. Among tier 1 studies, 53 cases were included in this analysis. The most common infection was pneumonia (31%) followed by primary or catheter-related bacteremia (21%) and urinary tract infection (17%). Different combinations of antibiotic classes were utilized in triple combinations, the most common being a polymyxin (colistin or polymyxin B, 86.8%), tigecycline (73.6%), aminoglycoside (43.4%), or carbapenem (43.4%). Clinical and microbiological failure occurred in 14/39 patients (35.9%) and 22/42 patients (52.4%), respectively. Overall mortality for patients treated with triple combination therapy was 35.8% (19/53 patients).. Triple combination therapy is being considered as a treatment option for CPKP. Polymyxin-based therapy is the backbone antibiotic in these regimens, but its effectiveness needs establishing in prospective clinical trials.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Drug Combinations; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Minocycline; Pneumonia; Polymyxin B; Polymyxins; Tigecycline; Treatment Outcome; Urinary Tract Infections

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

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

We sought to evaluate the effectiveness of the antibiotic treatment administered for infections caused by carbapenemase-producing Enterobacteriaceae. The PubMed and Scopus databases were systematically searched. Articles reporting the clinical outcomes of patients infected with carbapenemase-producing Enterobacteriaceae according to the antibiotic treatment administered were eligible. Twenty nonrandomized studies comprising 692 patients who received definitive treatment were included. Almost all studies reported on Klebsiella spp. In 8 studies, the majority of infections were bacteremia, while pneumonia and urinary tract infections were the most common infections in 12 studies. In 10 studies, the majority of patients were critically ill. There are methodological issues, including clinical heterogeneity, that preclude the synthesis of the available evidence using statistical analyses, including meta-analysis. From the descriptive point of view, among patients who received combination treatment, mortality was up to 50% for the tigecycline-gentamicin combination, up to 64% for tigecycline-colistin, and up to 67% for carbapenem-colistin. Among the monotherapy-treated patients, mortality was up to 57% for colistin and up to 80% for tigecycline. Certain regimens were administered to a small number of patients in certain studies. Three studies reporting on 194 critically ill patients with bacteremia showed individually significantly lower mortality in the combination arm than in the monotherapy arm. In the other studies, no significant difference in mortality was recorded between the compared groups. Combination antibiotic treatment may be considered the optimal option for severely ill patients with severe infections. However, well-designed randomized studies of specific patient populations are needed to further clarify this issue.

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; Carbapenems; Colistin; Critical Illness; Drug Therapy, Combination; Enterobacteriaceae; Humans; Minocycline; Pneumonia, Bacterial; Survival Analysis; Tigecycline; Urinary Tract Infections

Antimicrobial resistance to Pseudomonas aeruginosa is on the rise. In the absence of new anti-pseudomonal drugs, clinicians have had to resort to older antimicrobials such as colistin for the treatment of multi-drug resistant (MDR) strains. This polymyxin compound acts on the outer membrane of the bacteria resulting in its permeability and cell-death. Its bactericidal action is concentration-dependant. This antibiotic is mainly used as salvage therapy in the treatment of often life-threatening infections due to MDR P. aeruginosa blood-stream infections (BSI). Its potential nephrotoxicity and neurotoxicity have been overestimated and have limited the use in its intravenous form. A better understanding of its pharmacokinetics and pharmacodynamics, has facilitated more appropriate dosing strategies with a standard 9 million-unit daily-dose that should be adapted to kidney function. Combination treatment that involves the association of colistin with classical anti-pseudomonal treatment has rarely been clinically tested. In vitro synergy has been reported for certain combinations that could be used to prevent or limit the risk of induced resistance in MDR strains. Positioning colistin in antimicrobial strategies especially as a first-line treatment remains to be properly assessed.

Topics: Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Pseudomonas aeruginosa; Pseudomonas Infections; Salvage Therapy

A 77-year-old man had undergone left-lobe liver resection and a choledochojejunostomy six years previously, and thereafter he suffered from a postoperative relapse of cholangitis. He was admitted to our hospital due to liver abscesses and bacteremia caused by multidrug-resistant Pseudomonas aeruginosa. Empirical treatment with piperacillin/tazobactam was started, and the patient initially recovered. However, he developed a second case of sepsis caused by piperacillin/tazobactam-resistant P. aeruginosa bacteremia originating from a new liver abscess. We changed the piperacillin/tazobactam to colistin and flomoxef and continued the two antibiotics for one month. During the antibiotic therapy, the patient successfully underwent bile duct stent placement.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Cephalosporins; Cholangitis; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Kidney; Liver Abscess, Pyogenic; Male; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Pseudomonas Infections

Klebsiella pneumoniae carbapenemases (KPCs) were originally identified in the USA in 1996. Since then, these versatile β-lactamases have spread internationally among Gram-negative bacteria, especially K pneumoniae, although their precise epidemiology is diverse across countries and regions. The mortality described among patients infected with organisms positive for KPC is high, perhaps as a result of the limited antibiotic options remaining (often colistin, tigecycline, or aminoglycosides). Triple drug combinations using colistin, tigecycline, and imipenem have recently been associated with improved survival among patients with bacteraemia. In this Review, we summarise the epidemiology of KPCs across continents, and discuss issues around detection, present antibiotic options and those in development, treatment outcome and mortality, and infection control. In view of the limitations of present treatments and the paucity of new drugs in the pipeline, infection control must be our primary defence for now.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Colistin; Communicable Disease Control; Geography; Humans; Klebsiella Infections; Klebsiella pneumoniae; Minocycline; Tigecycline; Treatment Outcome

A 55-year old man developed a hemorrhagic pneumonia, likely due to infection with Kytococcus sedentarius during neutropenia following induction chemotherapy for acute myeloid leukemia. Severe mucosal barrier injury and the selective pressure of broad-spectrum antibiotics probably made it possible for this normally harmless commensal to penetrate the gut, spread through the blood stream, and invade the lungs.

Topics: Actinomycetales; Actinomycetales Infections; Acyclovir; Antineoplastic Combined Chemotherapy Protocols; Bacteremia; Bacterial Translocation; Cefepime; Cephalosporins; Clostridium Infections; Colistin; Cytarabine; Daunorubicin; Drug Therapy, Combination; Etoposide; Fatal Outcome; Hemoptysis; Humans; Hydroxyurea; Immunocompromised Host; Intestinal Mucosa; Leukemia, Myeloid, Acute; Male; Metronidazole; Middle Aged; Neutropenia; Pneumonia, Bacterial; Superinfection; Teicoplanin; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Bacterial Agents; Bacteremia; Carbapenem-Resistant Enterobacteriaceae; Colistin; Creatinine; Drug Resistance, Bacterial; Enterobacteriaceae Infections; Healthcare-Associated Pneumonia; Humans; Intention to Treat Analysis; Kaplan-Meier Estimate; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Sample Size; Sisomicin

The emergence of antibiotic-resistant bacteria has driven renewed interest in older antibacterials, including colistin. Previous studies have shown that colistin is less effective and more toxic than modern antibiotics. In vitro synergy studies and clinical observational studies suggest a benefit of combining colistin with a carbapenem. A randomised controlled study is necessary for clarification.. This is a multicentre, investigator-initiated, open-label, randomised controlled superiority 1:1 study comparing colistin monotherapy with colistin-meropenem combination therapy for infections caused by carbapenem-resistant Gram-negative bacteria. The study is being conducted in 6 centres in 3 countries (Italy, Greece and Israel). We include patients with hospital-associated and ventilator-associated pneumonia, bloodstream infections and urosepsis. The primary outcome is treatment success at day 14, defined as survival, haemodynamic stability, stable or improved respiratory status for patients with pneumonia, microbiological cure for patients with bacteraemia and stability or improvement of the Sequential Organ Failure Assessment (SOFA) score. Secondary outcomes include 14-day and 28-day mortality as well as other clinical end points and safety outcomes. A sample size of 360 patients was calculated on the basis of an absolute improvement in clinical success of 15% with combination therapy. Outcomes will be assessed by intention to treat. Serum colistin samples are obtained from all patients to obtain population pharmacokinetic models. Microbiological sampling includes weekly surveillance samples with analysis of resistance mechanisms and synergy. An observational trial is evaluating patients who met eligibility requirements but were not randomised in order to assess generalisability of findings.. The study was approved by ethics committees at each centre and informed consent will be obtained for all patients. The trial is being performed under the auspices of an independent data and safety monitoring committee and is included in a broad dissemination strategy regarding revival of old antibiotics.. NCT01732250 and 2012-004819-31; Pre-results.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacteria; Greece; Humans; Israel; Italy; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Pneumonia, Ventilator-Associated; Research Design; Thienamycins; Treatment Outcome; Urinary Tract Infections; Young Adult

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

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

This study aims to analyze the mortality and the length of ICU stay (LOS) of A. baumannii VAP compared to respiratory colonization in patients with mechanical ventilation (MV).. A prospective cohort study was performed in an ICU of adult patients (February 2010-June 2011). One hundred patients on MV with A. baumannii in lower respiratory airways were recruited, and classified as VAP or airways colonization according to CPIS criteria, with a punctuation ≥6. LOS, 30-days mortality, A. baumannii bacteremia, and clinical features including antibiotic therapy were recorded. Multivariate analysis (linear and Cox regression) and survival analysis (Kaplan-Meier curves) were performed.. Fifty-seven VAP and 43 colonized A. baumannii patients were analyzed. Among the A. baumannii strains, 99% were non-susceptible to carbapenems and the MIC90 of colistin was 0.12 mg/l. Therapy was appropriate in 94.6% of VAP patients, most of them with colistin 6 MIU/day, although in 13 (23.6%) cases colistin was started 48 hours after the onset of VAP. Mortality was similar in both groups (VAP 24.6% vs. colonized 27.9%, p = 0.7). Bacteremia and acute kidney insufficiency were associated with decreased survival (p = 0.02 and p = 0.04, respectively) in VAP patients. LOS was 21.5 (11.5-42.75) vs. 9 (6-22) days for VAP and colonized patients (p = 0.004). VAP (p = 0.003) and age (p = 0.01) were independently related to a longer LOS.. Multidrug-resistant A. baumannii VAP treated with colistin does not have a different mortality compared to lower airways colonization, among patients on mechanical-ventilation, in a setting of high susceptibility to colistin of A. baumannii.

Topics: Acinetobacter baumannii; Adult; Bacteremia; Carbapenems; Colistin; Disease-Free Survival; Drug Resistance, Multiple, Bacterial; Female; Follow-Up Studies; Humans; Male; Pneumonia, Ventilator-Associated; Prospective Studies; Survival Rate

Selective digestive decontamination (SDD) and selective oropharyngeal decontamination (SOD) are effective in improving survival in patients under intensive care. In this study possible differential effects in surgical and non-surgical patients were investigated.. This was a post hoc subgroup analysis of data from a cluster-randomized multicentre trial comparing three groups (SDD, SOD or standard care) to quantify effects among surgical and non-surgical patients. The primary study outcome was 28-day mortality rate. Duration of mechanical ventilation, duration of intensive care unit (ICU) and hospital length of stay, and bacteraemia rates were secondary outcomes.. The subgroup analyses included a total of 2762 surgical and 3165 non-surgical patients. Compared with standard care, adjusted odds ratios (ORs) for mortality were comparable in SDD-treated surgical and non-surgical patients: 0·86 (95 per cent confidence interval 0·69 to 1·09; P = 0·220) and 0·85 (0·70 to 1·03; P = 0·095) respectively. However, duration of mechanical ventilation, ICU stay and hospital stay were significantly reduced in surgical patients who had SDD. SOD did not reduce mortality compared with standard treatment in surgical patients (adjusted OR 0·97, 0·77 to 1·22; P = 0·801); in non-surgical patients it reduced mortality (adjusted OR 0·77, 0·63 to 0·94; P = 0·009) by 16·6 per cent, representing an absolute mortality reduction of 5·5 per cent with number needed to treat of 18.. Subgroup analysis found similar effects of SDD in reducing mortality in surgical and non-surgical ICU patients, whereas SOD reduced mortality only in non-surgical patients. The hypothesis-generating findings mandate investigation into mechanisms between different ICU populations.

Topics: Administration, Oral; Amphotericin B; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacteremia; Cefotaxime; Cluster Analysis; Colistin; Critical Care; Cross Infection; Decontamination; Digestive System Diseases; Drug Combinations; Female; Hospital Mortality; Humans; Infusions, Intravenous; Intubation, Gastrointestinal; Length of Stay; Male; Middle Aged; Oropharynx; Pharyngeal Diseases; Respiration, Artificial; Tobramycin

One hundred and eighteen (118) episodes of bacteremia and fungemia in children with cancer were compared to 401 episodes of bacteremia and fungemia in adults with cancer to assess differences in etiology, risk factors and outcome. A retrospective univariate analysis was performed of all episodes of bacteremia in national pediatric and adult cancer institutions appearing in 1990-1996. A total of 519 episodes of bacteremia were assessed and compared. Both cancer centers differed in prophylactic antibiotic policies. About 50% of adults but less than 5% of children received quinolone prophylaxis during neutropenia, even though the empiric antibiotic therapeutic strategy was similar. There were differences in etiology between the groups: staphylococci and Stenotrophomonas maltophilia were more frequently observed in children (P<0.01), Pseudomonas aeruginosa and Acinetobacter spp. in adults (P<0.05). Gram-positive bacteremia was surprisingly more commonly observed in adults (65.7% vs 33.3%, P<0.01). Mixed polymicrobial bacteremia occurred more commonly in adults (31.8% vs 7.6%, P<0.001) than in children. Analysis of risk factors did not observe differences in risk factors except for underlying disease (acute leukemia was more frequently observed in children -48.3% vs adults 33.7%, P<0.05 and prophylaxis: (prior prophylaxis with quinolones was more common in adults (47.5%) than in children (2.5%) P<0.0001). Overall and attributable mortality in pediatric bacteremia was significantly lower than in adults (P<0.03).

Topics: Adult; Analysis of Variance; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotic Prophylaxis; Antifungal Agents; Antineoplastic Agents; Bacteremia; Child; Colistin; Fluconazole; Fungemia; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Neoplasms; Neutropenia; Ofloxacin; Penicillin V; Penicillins; Retrospective Studies; Risk Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) in patients hospitalized in intensive care units (ICUs) is an important and challenging complication, including in patients with coronavirus disease 2019 (COVID-19). Considering the poor lung penetration of most antibiotics, including intravenous colistin due to the poor pharmacokinetics/pharmacodynamics at the infection site, the choice of the best antibiotic regimen is still being debated.. This single-centre, observational study was conducted from March 2020 to August 2022, and included all patients hospitalized consecutively with VAP and concomitant bloodstream infection due to CRAB in the COVID-ICU. The main goal of the study was to evaluate risk factors associated with survival or death at 30 days from VAP onset. A propensity score for receiving therapy was added to the model.. During the study period, 73 patients who developed VAP and concomitant positive blood cultures caused by CRAB were enrolled in the COVID-ICU. Of these patients, 67 (91.7%) developed septic shock, 42 (57.5%) had died at 14 days and 59 (80.8%) had died at 30 days. Overall, 54 (74%) patients were treated with a colistin-containing regimen and 19 (26%) were treated with a cefiderocol-containing regimen. Cox regression analysis showed that chronic obstructive pulmonary disease and age were independently associated with 30-day mortality. Conversely, cefiderocol-containing regimens and cefiderocol + fosfomycin in combination were independently associated with 30-day survival, as confirmed by propensity score analysis.. This real-life study in patients with bacteraemic VAP caused by CRAB provides useful suggestions for clinicians, showing a possible benefit of cefiderocol and its association with fosfomycin.

Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Bacteremia; Carbapenems; Cefiderocol; Colistin; COVID-19; Fosfomycin; Humans; Pneumonia, Ventilator-Associated

The global prevalence of colistin-resistant Klebsiella pneumoniae (ColRkp) facilitated by chromosomal and plasmid-mediated Ara4N or PEtN-remodeled LPS alterations has steadily increased with increased colistin usage for treating carbapenem-resistant K. pneumoniae (CRkp). Our study demonstrated the rising trend of ColRkp showing extensively and pandrug-resistant characteristics among CRkp, with a prevalence of 28.5%, which was mediated by chromosomal mgrB, pmrB, or phoQ mutations (91.5%), and plasmid-mediated mcr-1.1, mcr-8.1, mcr-8.2 alone or in conjunction with R256G PmrB (8.5%). Several genetic alterations in mgrB (85.1%) with increased expressions of Ara4N-related phoPQ and pmrK were critical for establishing colistin resistance in our isolates. In this study, we discovered the significant associations between extensively drug-resistant bacteria (XDR) and pandrug-resistant bacteria (PDR) ColRkp in terms of moderate, weak or no biofilm-producing abilities, and altered expressions of virulence factors. These ColRkp would therefore be very challenging to treat, emphasizing for innovative therapy to combat these infections. Regardless of the underlying colistin-resistant mechanisms, colistin-EDTA combination therapy in this study produced potent synergistic effects in both in vitro and in vivo murine bacteremia, with no ColRkp regrowth and improved animal survival, implying the significance of colistin-EDTA combination therapy as systemic therapy for unlocking colistin resistance in ColRkp-associated bacteremia.

Topics: Animals; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; Drug Resistance, Bacterial; Edetic Acid; Klebsiella Infections; Klebsiella pneumoniae; Mice; Microbial Sensitivity Tests; Prevalence

Ceftolozane-tazobactam is an emerging ‎treatment for severe infections caused by multidrug-resistant (MDR) Pseudomonas ‎aeruginosa. However, limited ‎data support its use in bacteremia treatment. This study aimed to assess the effectiveness of the treatment of MDR P. aeruginosa bacteremia using ceftolozane-‎tazobactam-based or colistin-based regimens. ‎ PATIENTS AND METHODS: This retrospective, cohort, multicentre study included adult patients with ‎MDR P. aeruginosa bacteremia treated with either ceftolozane-tazobactam or ‎colistin, between September 2018 and August 2021, at four hospitals in Saudi ‎Arabia. The primary endpoint was the 30-day risk-adjusted mortality. Secondary endpoints included the 14-day risk of mortality, bacterial eradication, and clinical ‎success. Cox proportional hazards ‎regression and relative risk estimation were used for analysis, as appropriate. ‎ RESULTS: In total, 46 patients were included; 17 patients received ceftolozane-‎tazobactam-based regimen, and 29 received a colistin-based regimen. There was no association with the use of ‎ceftolozane-tazobactam compared to colistin and the 30-day risk-adjusted mortality ‎‎(hazard ratio [HR] ‎0.58, 95% confidence interval [CI] 0.16-2.13, P = 0.42). Also, the ‎‎14-day risk of mortality and bacterial eradication were not different between the ‎ceftolozane-tazobactam and colistin regimens, HR 2.1, 95% CI 0.42-10.48; P = 0.36; and ‎relative risk (RR) 0.65; 95% CI 0.28-1.52; P = 0.30; respectively. On the other hand, ‎ceftolozane-tazobactam use was associated with higher clinical success than colistin ‎‎(RR 1.84, 95% CI 1.11-3.06: P = 0.021).‎ CONCLUSION: The risk of mortality of MDR P.aeruginosa bacteremia was ‎similar when treated with ceftolozane-tazobactam-based or colistin-based antimicrobial regimens. A higher clinical success was observed with the ceftolozane-‎tazobactam-based regimen compared to the colistin-based regimen. ‎.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Cephalosporins; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Tazobactam

The emergence of carbapenem-resistant Enterobacterales (CRE) has become a serious and significant public health threat worldwide, owing to the limited antimicrobial therapy options, and the elevated mortality rates associated with these infections.. To present an update on the epidemiology of CRE bloodstream infections among hospitalised patients reported under the Group for Enteric, Respiratory and Meningeal Diseases Surveillance in South Africa (GERMS-SA) between January 2019 and December 2020.. Patients of all ages with CRE bacteraemia were included and isolates, when available, were sent to the reference laboratory for confirmatory testing and molecular characterisation. Multivariable logistic regression analysis was performed to assess factors associated with in-hospital mortality.. We included 2 144 patients with CRE bacteraemia with a median age of 33 (interquartile range 1 - 51) years, of whom 1 145 (54.2%) were male. Klebsiella pneumoniae accounted for 79.8% of infections (n=863/1 082), of which 89.5% (n=611/683) were healthcare associated (HA). The most common carbapenemase genes were carbapenem-hydrolysing oxacillinase-48 (blaOXA-48-like) (76.8%; n=761/991), New Delhi metallo-β-lactamase (blaNDM) (21.1%; n=209/991) and Verona integron-encoded metallo-β-lactamase (blaVIM) (1.3%; n=13/991). None of the screened isolates with a colistin minimum inhibitory concentration >2 μg/mL harboured the mobilised colistin resistance (mcr)-1 to mcr-5 genes. The crude in-hospital mortality rate was 36.6% (n=377/1 029). Patients aged ≥60 years (v. 1.6 - 9 years) (adjusted odds ratio (aOR) 4.53; 95% confidence interval (CI) 2.21 - 9.28), those with comorbidities (diabetes, malignancy, renal and/or cardiovascular failure) (aOR 1.72; 95% CI 1.17 - 2.52), those with altered mental state (aOR 5.36; 95% CI 3.21 - 8.92) and those with previous antimicrobial use (aOR 1.88; 95% CI 1.27 - 2.77) had increased odds of in-hospital mortality.. The epidemiology of CRE bloodstream infections remained similar compared with the previous surveillance report. Most infections were HA and caused by OXA-48-like carbapenemase-producing K. pneumoniae with no plasmid-mediated colistin resistance. Standard infection control measures should be strengthened.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Carbapenems; Child; Child, Preschool; Colistin; Female; Humans; Infant; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; South Africa; Tertiary Care Centers; Young Adult

Concerns regarding carbapenem-resistant Klebsiella pneumoniae (CR-Kp), especially in bloodstream infections (BSIs), are continuing to increase worldwide. Several novel agents with activity against BSI CR-Kp have been approved or are in late-stage clinical development. In this study, the antibacterial effects of ceftazidime/avibactam (CZA), aztreonam/avibactam (AZA), meropenem/vaborbactam (MEV), imipenem-cilastatin/relebactam (ICR) and eravacycline (ERV) against three colistin-resistant CR-Kp (COLR-Kp) and four CZA-resistant CR-Kp (CZAR-Kp) were tested by time-kill assay. Klebsiella pneumoniae ATCC® BAA-1705TM was used as a control strain. Two COLR-Kp isolates carried the blaKPC-2 gene and four CAZR-Kp isolates carried metallo-β-lactamase genes. The results revealed that ERV resulted in re-growth of seven tested isolates. CZA and MEV showed a bactericidal effect against isolates harbouring blaKPC-2. ICR reduced the population of six isolates to >5 log10 CFU/mL compared with the initial count. AZA showed a bactericidal effect (>5 log10 CFU/mL) against seven isolates and a bacteriostatic effect (<3 log10 CFU/mL) against one CZAR-Kp isolate. Therefore, AZA and ICR are effective therapeutic candidates for COLR-Kp and CZAR-Kp isolates.

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Aztreonam; Bacteremia; beta-Lactamase Inhibitors; Boronic Acids; Carbapenem-Resistant Enterobacteriaceae; Ceftazidime; Cilastatin; Colistin; Drug Combinations; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Tetracyclines

Colistin is an, antibiotic used to treat carbapenem-resistant

Topics: Acinetobacter baumannii; Acinetobacter Infections; Acute Kidney Injury; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Kidney Function Tests; Male; Middle Aged; Organ Dysfunction Scores; Risk Factors

Polymyxins (colistin) have emerged for the treatment of carbapenem resistant (CR) gram-negative infections. There is a paucity of data on treatment outcomes and adverse effects of high-dose colistin treatment in Pakistan. The aim of this study was to determine the efficacy and toxicity of colistin in CR bacteremia, including patients with renal failure and on hemodialysis, and to determine patient outcomes.. This prospective cohort study was performed from May to December 2017 at Sindh Institute of Urology and Transplantation, Karachi, Pakistan. Patients aged >18 years with documented gram-negative bacteremia were included. Data were compared between those who received colistin and those who did not, including risk factors for CR bacteremia, bacterial clearance, adverse effects, and all-cause mortality up to 14 days of follow-up.. The study included 137 patients, 73 (53.3%) in the colistin group and 64 (46.7%) in the non-colistin group. Patients in the colistin group were 1.47 times more likely to have died by day 14 of follow-up as compared to those in the non-colistin group (19.2% vs 7.8%; relative risk 1.47, p= 0.05). Patients in both groups achieved more than 80% bacteriological clearance. The colistin group patients were less likely to have received appropriate empirical antibiotics as compared to the non-colistin group patients (4.1% vs 62.5%; relative risk 0.09, p< 0.001). Factors significantly associated with mortality were inappropriate empirical antibiotics and acute renal failure. Of the 73 patients in the colistin group, 27 (37.0%) developed reversible neurological adverse effects. Patients with renal insufficiency, not on hemodialysis, were evaluated for colistin nephrotoxicity. Creatinine decreased from 8.08 mg/dl at baseline to 4.85 mg/dl on day 7 in the colistin group, and from 6.5 mg/dl to 3.9 mg/dl in the non-colistin group. Patients with normal renal function had no significant rise in serum creatinine.. Colistin is efficacious in clearing bacteremia even in patients with impaired renal function. The adverse effects were found to be minimal and reversible. We recommend the use of colistin in combination with carbapenems for CR gram-negative bacteria in renal failure. Most importantly, however, this study highlights the role of empirical colistin treatment in patients with risk factors for CR bacteremia.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacteremia; Carbapenems; Colistin; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Pakistan; Prospective Studies; Treatment Outcome

Topics: Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Multilocus Sequence Typing; Mutation; Plasmids

Antimicrobial treatments for carbapenem-resistant Enterobacteriaceae (CRE) bacteremia are limited, with colistin-based regimens being a primary therapy. Ceftazidime-avibactam is an emerging treatment for various CRE infections. Our study aimed to assess ceftazidime-avibactam effectiveness compared with colistin in patients with CRE bacteremia.. This retrospective, multi-centre study included adult patients with CRE bacteremia treated with ceftazidime-avibactam or colistin, between September 1, 2017 and December 1, 2020, at two tertiary centres in Saudi Arabia. The risk of 14-day mortality was compared between recipients of ceftazidime-avibactam versus colistin, using Cox multivariable regression, adjusted for Pitt score, Charlson index score, and treatment with chemotherapy and immunosuppressive agents.. In total, 61 patients were enrolled; 32 received ceftazidime-avibactam, and 29 received colistin. The adjusted risk for 14-day mortality was lower in the ceftazidime-avibactam group than the colistin group (hazard ratio [HR] 0.32; 95% confidence interval [CI] 0.10-0.99; p = 0.049), while the crude 14-day mortality did not differ between the two antibiotics (HR, 0.59; 95% CI 0.21-1.66; p = 0.32). The clinical success rate was higher with the use of ceftazidime-avibactam versus colistin (46.8% versus 20.4%, respectively; p = 0.047).. Ceftazidime-avibactam was associated with a lower risk of 14-day mortality than colistin in patients with CRE bacteremia.

Topics: Adult; Azabicyclo Compounds; Bacteremia; Carbapenem-Resistant Enterobacteriaceae; Ceftazidime; Colistin; Drug Combinations; Humans; Microbial Sensitivity Tests; Retrospective Studies

The resistance rate of Klebsiella pneumoniae to commonly used antibiotics has been increasing rapidly, causing serious concern among clinicians and microbiologists. Resistance to carbapenems in K. pneumoniae is increasing dramatically in Chinese hospitals. Here we report the genome sequence of an NDM-1 and KPC-2 co-producing K. pneumoniae (CRKP380) isolated from a bloodstream infection in Hangzhou, China.. The whole genome sequence of strain CRKP380 was determined using an Illumina NovaSeq 6000 platform. Antimicrobial resistance genes (ARGs) were identified using the BacWGSTdb server. The phylogenetic relationship between strain CRKP380 and other K. pneumoniae strains isolated from Hangzhou currently deposited in the NCBI GenBank database was analysed using a core genome-based single nucleotide polymorphism strategy.. Klebsiella pneumoniae CRKP380 was resistant to all antibiotics tested except tigecycline and colistin. The genome sequence of K. pneumoniae CRKP380 consisted of 75 contigs comprising 5 590 460 bp. According to the Pasteur multilocus sequence typing (MLST) scheme, CRKP380 belongs to ST11. Eight ARGs were identified in CRKP380, including two carbapenemase genes (bla. Here we report the genome sequence of a K. pneumoniae ST11 clinical strain co-carrying bla

Topics: Bacteremia; beta-Lactamases; Colistin; Drug Resistance, Multiple, Bacterial; Genome Size; Genome, Bacterial; High-Throughput Nucleotide Sequencing; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests; Multilocus Sequence Typing; Phylogeny; Tigecycline; Whole Genome Sequencing

Topics: Animals; Bacteremia; Colistin; Humans; Salmonella; Salmonella enterica; Salmonella Infections, Animal

Colistin remains a last-line antibiotic for the treatment of infections by multidrug-resistant Acinetobacter species. However, mortality rates are high in patients with Acinetobacter infection receiving colistin treatment. This multicentre study evaluated whether colistin susceptibility, additional antimicrobial agents or other prognostic factors influenced the clinical outcomes of patients receiving colistin treatment for Acinetobacter bacteraemia. This retrospective study enrolled 122 adults receiving colistin for monomicrobial Acinetobacter bacteraemia at six medical centres in the ACTION Study Group over an 8-year period. Clinical information, antimicrobial susceptibility and colistin resistance determinants were analysed. The primary outcome measure was 14-day mortality. Among 122 patients, 18 and 104 were infected with colistin-resistant (ColR) isolates [minimum inhibitory concentration (MIC) ≥4 mg/L] and colistin-susceptible (ColS) isolates (MIC ≤2 mg/L), respectively. Patients infected with ColR and ColS isolates did not differ significantly with regard to Charlson comorbidity index, invasive procedures, sources of bacteraemia, disease severity and 14-day mortality rate (44.4% vs. 34.6%; P = 0.592). No specific additional antimicrobial agent was independently associated with higher or lower mortality. Coronary artery disease, higher Acute Physiology and Chronic Health Evaluation (APACHE) II score and bacteraemia caused Acinetobacter baumannii were independent risk factors associated with 14-day mortality. Mechanisms of colistin resistance were associated with amino acid variants in the pmrCAB operon. Finally, previously unreported Acinetobacter nosocomialis amino acid variants related to colistin resistance were identified. In conclusion, colistin susceptibility and colistin combination antimicrobial treatment were not associated with decreased 14-day mortality in patients with Acinetobacter bacteraemia receiving colistin treatment.

Topics: Acinetobacter; Acinetobacter baumannii; Acinetobacter Infections; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Colistin; Comorbidity; Drug Resistance, Bacterial; Female; Genome, Bacterial; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Operon; Prognosis; Retrospective Studies; Risk Factors; Treatment Outcome

Carbapenem-resistant gram negative pathogen (CR-GNP) infection in burn patients is a growing concern since treatment options are limited and resistance to the main line of treatment, colistin, is increasing. The goal of this study was to compare treatment outcomes of colistin monotherapy versus colistin-based combination therapy for CR-GNP bacteremia in burn patients. A retrospective observational study was conducted between 2014 and 2017 in Hangang Sacred Heart Hospital located in Seoul, South Korea. Among the burn patients admitted to the burn intensive care unit with CR-GNP bacteremia due to wound infections, colistin monotherapy or colistin-based combination therapy were investigated. We determined both eradication rate within seven days as well as mortality rate within 30 days. A total of 84 burn patients with CR-GNP bacteremia were analyzed-32 were treated with colistin monotherapy and 52 with colistin-based combination therapy. We found that eradication rate within 7 days and 30-day mortality rate were not significantly different between the two groups (71.9% versus 75.0%, P = 0.752 and 31.2% versus 38.5%, P = 0.503). In the Cox regression analysis, Charlson's comorbidity index, renal replacement therapy before colistin use, and duration of antibiotics were associated with 30-day mortality (HR, 1.23; 95% CI, 1.02-1.49; P = 0.030, HR, 2.28; 95% CI, 1.05-4.94; P = 0.037 and HR, 0.94; 95% CI, 0.89-0.99, P = 0.042, respectively). Colistin-based combination therapy did not show significant differences with regard to microbiologic and clinical outcomes compared with colistin monotherapy.

Topics: Adult; Aged; Bacteremia; Burns; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Republic of Korea; Retrospective Studies

The aim of this study was to determine the effect of colistin resistance and other predictors on fatality among patients with Klebsiella pneumoniae bloodstream infections (Kp-BSI) and to describe the effect of amikacin and tigecycline on the outcome in an OXA-48 dominant country.. This was a retrospective study performed among patients >16 years of age in a tertiary hospital with 465 beds. All cases had ≥1 positive blood culture for K. pneumoniae 48 h after admission.. Among 210 patients with Kp-BSI, the 30-day mortality rate after isolation of the microorganism was 58%. The rate of carbapenem resistance was higher (64% vs. 38%, p < 0.001) and the colistin minimum inhibitory concentration (MIC) was elevated (7 vs. 4, p < 0.029) among the patients who died. Among the colistin-resistant K. pneumoniae, the rates of OXA-48, ST101, and NDM-1 were 78%, 67%, and 35%, respectively. Amikacin was added to the treatment of 13 patients with carbapenem and colistin-resistant Kp-BSI and 77% survived (p < 0.001). Tigecycline was added to the treatment of 24 patients with carbapenem and colistin-resistant Kp-BSI, and the 30-day mortality rate was 71% (p = 0.576). In the multivariate analysis, carbapenem resistance (odds ratio (OR) 5.2, 95% confidence interval (CI) 2.47-10.9, p < 0.001) and increasing APACHE II score (OR 1.19, 95% CI 1.12-1.26, p < 0.001) were significantly associated with 30-day mortality. The addition of amikacin to the treatment regimen (OR 0.05, 95% CI 0.01-0.23, p < 0.001) was significantly beneficial.. Carbapenem resistance, increasing MIC of colistin, and the lungs as the source of the infection were significantly associated with 30-day mortality. The empirical use of combined active aminoglycosides was found to be beneficial in the treatment of colistin-resistant K. pneumoniae infections.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amikacin; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Carbapenems; Colistin; Drug Resistance, Bacterial; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Risk Factors; Tertiary Care Centers; Tigecycline; Young Adult

Carbapenem-resistant. This retrospective multicenter propensity score-matching analysis was conducted in the Korea by reviewing the medical records of adult patients with CRAB bacteremia between January 2012 and March 2015. Early colistin therapy was defined as intravenous colistin administration for > 48 hours within five days after the blood culture collection. To identify the risk factors associated with the 28-day mortality in CRAB bacteremia, the clinical variables of the surviving patients were compared to those of the deceased patients.. Of 303 enrolled patients, seventy-six (25.1%) patients received early colistin therapy. The 28-day mortality was 61.4% (186/303). Fatal or rapidly-fatal McCabe classifications, intensive care unit admission, Sequential Organ Failure Assessment scores ≥ 8, vasopressor use, and acute kidney injury were statistically independent poor prognostic factors. Catheter-related infection and early colistin therapy (adjusted odds ratio [aOR], 0.45; 95% confidence interval [CI], 0.21-0.94) were independent favorable prognostic factors associated with 28-day mortality in patients with CRAB bacteremia. Early colistin therapy was still significantly associated with lower 28-day mortality in the propensity score-matching analysis (aOR, 0.31; 95% CI, 0.11-0.88).. This study suggests that early colistin therapy might help reduce the mortality of patients with CRAB bacteremia.

Topics: Acinetobacter baumannii; Administration, Intravenous; Aged; Anti-Bacterial Agents; Bacteremia; Blood Culture; Colistin; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Humans; Intensive Care Units; Kaplan-Meier Estimate; Male; Middle Aged; Odds Ratio; Prognosis; Propensity Score; Republic of Korea; Retrospective Studies

Topics: Acinetobacter baumannii; Bacteremia; Carbapenems; Colistin; Humans; Prognosis; Propensity Score; Solanum tuberosum

Topics: Acinetobacter baumannii; Aged; Bacteremia; Colistin; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Humans; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Multivariate Analysis; Risk Factors; Survival Analysis

The objectives of the present study were to identify risk factors for development of acute kidney injury (AKI) during the treatment of bacteraemia due to carbapenem non-susceptible Gram-negative bacteria (CnS-GNB) and its role on mortality. Data of all patients with bacteraemia by CnS-GNB in the intensive care unit of a tertiary hospital from 2012 to 2016 were included. AKI was defined by AKIN criteria. Secondary outcomes were AKI development in patients treated with colistin and predictors of 14-day mortality. Among 285 episodes of bacteraemia due to CnS-GNB, 84 (29.5%) developed AKI. Multivariate analysis revealed that obesity, septic shock, maximum noradrenaline dose and eGFR<60 mL/min/1.73m² upon bacteraemia onset were independently associated with development of AKI. Out of 228 patients receiving colistin, 64 (28.1%) developed AKI. Multivariate analysis found the same factors as before in addition to voriconazole administration. Fourteen-day mortality was 34.2% and was independently associated with bacteraemia by Pseudomonas aeruginosa, AKI during bacteraemia treatment, maximum noradrenaline dose, SAPS II and SOFA scores upon bacteraemia onset, whereas appropriate combination therapy and catheter-related bacteraemia were independently associated with better survival. AKI was a frequent complication of bacteraemia by CnS-GNB and was associated with septic shock and baseline renal function impairment. Mortality was higher among patients that developed AKI due to bacteraemia. Colistin should be considered a safe therapeutic option for treating such infections.

Topics: Acute Kidney Injury; Adult; Aged; Anti-Bacterial Agents; Bacteremia; Carbapenems; Colistin; Critical Illness; Drug Resistance, Bacterial; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Retrospective Studies; Risk Assessment; Risk Factors

We describe a case of one patient with cystic fibrosis who developed a pan-resistant Burkholderia cepacia complex rapidly progressive bacteraemic pneunonia, following bilateral lung transplantation. The patient was treated with a targeted combination antibiotic therapy (meropenem plus ceftazidime/avibactam plus high doses of nebulized colistimethate sodium). Evolution of the disease was complicated by multiple organ system dysfunction. Finally, clinical improvement and microbiological cure was achieved.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Burkholderia cepacia complex; Burkholderia Infections; Colistin; Cystic Fibrosis; Drug Resistance, Multiple, Bacterial; Humans; Lung Transplantation; Male; Pneumonia, Bacterial; Treatment Outcome; X-Rays

Topics: Anti-Bacterial Agents; Autistic Disorder; Bacteremia; Child; Chryseobacterium; Ciprofloxacin; Colistin; Drug Resistance, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Carbapenem-resistant Acinetobacter baumannii infections are a major public health problem worldwide, requiring the use of "old" antibiotics such as polymyxin B and E (colistin). However, there is concern regarding the emergence of isolates resistant to these antibiotics.. We report a case of a 64-year-old mestizo man hospitalized in an intensive care unit of a health institution in Colombia with identification and clinical and molecular typing of a colistin- and carbapenem-resistant A. baumannii isolate with mechanisms of resistance to colistin not previously reported, causing bacteremia.. We have identified a strain of A. baumannii with mechanisms of resistance to colistin not previously reported in a patient with bacteremia who required treatment with multiple antibiotic schemes and had an adequate response.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Bacteremia; Catheter-Related Infections; Catheters, Indwelling; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Male; Middle Aged

Bacteraemia due to carbapenem-resistant gram-negative bacteria is challenging. This study examined the burden of carbapenem and colistin resistance in Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii bacteraemia in Oman.. Adult patients admitted to Sultan Qaboos University Hospital between January 1, 2007 and December 31, 2016 with positive blood cultures for P. aeruginosa, A. baumannii, or K. pneumoniae were identified. Rates of carbapenem resistance, trends in prevalence, and 30-day all-cause mortality were examined.. Two hundred and twenty-seven (29.8%) of 761 bacteraemia cases due to these three isolates were carbapenem-resistant, with 87.2% being healthcare-associated. A. baumannii caused 52% of all carbapenem-resistant bacteraemia, K. pneumoniae caused 30%, and P. aeruginosa caused 18%. Rates of carbapenem resistance in P. aeruginosa, A. baumannii, and K. pneumoniae bacteraemia increased from 20%, 67%, and 0%, respectively, in 2007 to 25%, 86%, and 35%, respectively, in 2016. Seventeen (7.9%) carbapenem-resistant bacteraemia cases were also colistin-resistant. Thirty-day all-cause mortality was 62% in patients with carbapenem-resistant bacteraemia and 22% in patients with carbapenem-sensitive bacteraemia.. The prevalence of carbapenem-resistant K. pneumoniae, A. baumannii, and P. aeruginosa bacteraemia is increasing alarmingly in Oman, with a large proportion of K. pneumoniae and P. aeruginosa demonstrating additional resistance to colistin. Patients with carbapenem-resistant bacteraemia had higher 30-day all-cause mortality.

Topics: Acinetobacter baumannii; Adult; Anti-Bacterial Agents; Bacteremia; Carbapenems; Colistin; Drug Resistance, Bacterial; Female; Humans; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Oman; Prevalence; Pseudomonas aeruginosa

External validation of the INCREMENT-CPE risk score (ICS) for 30-day all-cause mortality is needed. There is also scarce information about whether colistin resistance influences the prognosis of carbapenem-resistant Klebsiella pneumoniae (CRKp) bacteraemia. In this study, the ability of ICS to predict all-cause mortality in the KAPECOR cohort was calculated using the area under the receiver operating characteristic (AUROC) curve. The association of colistin resistance with mortality was studied. The ICS showed an AUROC curve of 0.77 (95% CI 0.68-0.86). A cut-off of 8 points showed 96.8% sensitivity and 50.7% specificity. Mortality of low-risk patients was not different in those treated with monotherapy versus combination therapy. However, mortality of high-risk patients treated with combination therapy (37.8%) was significantly lower than in those treated with monotherapy (68.4%) (P = 0.008). To study the prognostic significance of colistin resistance, 83 selected cases of bacteraemia due to colistin-susceptible CRKp were obtained from the INCREMENT cohort for comparison. Colistin resistance could not be shown to be associated with higher mortality in either the high-risk ICS group [adjusted odds ratio (aOR) = 1.56, 95% CI 0.69-3.33; P = 0.29] or in 37 ICS-matched pairs (aOR = 1.38, 95% CI 0.55-3.42; P = 0.49), or in a sensitivity analysis including only KPC isolates (aOR = 1.81, 95% CI 0.73-4.57; P = 0.20), but the precision of estimates was low. These results validate ICS for all-cause mortality and to optimise targeted therapy for CRKp bacteraemia. Colistin resistance was not clearly associated with increased mortality.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Carbapenem-Resistant Enterobacteriaceae; Clinical Decision Rules; Colistin; Drug Resistance, Bacterial; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Prognosis; ROC Curve; Survival Analysis

To identify plasmid-mediated colistin resistance in clinical Enterobacteriaceae isolates in Oman, where this resistance mechanism has not been encountered yet.. Twenty-two colistin-resistant Enterobacteriaceae clinical isolates collected between July 2014 and June 2016 in a tertiary care hospital in Muscat were screened by PCR for the mcr-1 and mcr-2 genes. The strain identified as mcr-1 positive was genotyped and its antibiotic susceptibility was established. The mcr-1 containing plasmid was mobilized into Escherichia coli K-12 and its sequence was determined.. A single E. coli isolate (OM97) carrying mcr-1 gene was identified, while no strains carrying the mcr-2 gene was found. E. coli OM97 was isolated in June 2016 from blood culture of a male patient with multiple comorbidities. It belonged to ST10. Beyond colistin, it was resistant to amoxicillin-clavulanic acid, piperacillin-tazobactam, amikacin, ciprofloxacin, tetracycline, and cotrimoxazole. The mcr-1 gene was located on a conjugative IncI2-type plasmid of 63722 bp size, which did not harbor any further resistance genes. The genetic surrounding of the mcr-1 gene lacked the ISApl1 element.. Although colistin resistance caused by the mcr-1 gene is not common in our collection of clinical isolates, the occurrence of the plasmid-mediated colistin resistance in an E. coli ST10 strain is of concern as this clonal group was already shown to spread ESBL genes and quinolone resistance worldwide. It is especially worrisome that as the mcr-1 gene occurred in a non-ESBL, carbapenem-susceptible E. coli strain, current susceptibility testing algorithms may not detect its presence.

Topics: Amikacin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bacteremia; Ciprofloxacin; Colistin; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Gene Expression; Humans; Membrane Proteins; Microbial Sensitivity Tests; Oman; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Plasmids; Protein Isoforms; Tetracycline; Trimethoprim, Sulfamethoxazole Drug Combination

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

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

To evaluate the impact of high-dose (HD) carbapenem-based combination therapy on clinical outcome in patients with monomicrobial carbapenem-resistant Klebsiella pneumoniae (CR-KP) bloodstream-infection (BSI).. Post hoc analysis of all adult patients with CR-KP BSI who were treated with a combination antibiotic regimen, collected over a six-year period in six large Italian teaching hospitals. To control for confounding effects of HD carbapenem combination on 14-day mortality, a multivariate Cox regression analysis was performed. Due to imbalances between patients, a propensity score for receiving HD carbapenem was added to the model.. 595 patients with CR-KP BSI were analysed, 77% of isolates showed a carbapenem MIC ≥16 mg/L, 428 (71.9%) received HD carbapenem-based combination therapy. Overall, 127 patients (21.3%) died within 14 days after BSI onset. Multivariate analysis showed the Charlson comorbidity index (HR 1.31, 95%CI 1.20-1.43, P <0.001), septic shock at BSI onset (HR 3.14, 95%CI 2.19-4.50, P <0.001), and colistin-resistant strain (HR 1.52, 95%CI 1.02-2.24, P = 0.03) were independently associated with 14-day mortality, whereas admission to surgical ward (HR 0.44, 95%CI 0.25-0.78, P = 0.005) and HD carbapenem use (HR 0.69, 95%CI 0.47-1.00, P = 0.05) were protective factors. When adjusted for the propensity score, HD carbapenem use showed a greater protective effect (HR 0.64, 95%CI 0.43-0.95, P = 0.03). Stratifying the model for carbapenem MIC, the benefit of HD carbapenem was also observed for strains with carbapenem MIC ≥16 mg/L.. In patients receiving combination therapy for CR-KP BSI, the use of HD carbapenem seems to be associated with better outcome, even in the presence of high-level carbapenem resistance.

Topics: Aged; Bacteremia; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Gentamicins; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Minocycline; Propensity Score; Tertiary Care Centers; Tigecycline; Treatment Outcome

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

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

This article describes the emergence of resistance and predictors of fatality for 1556 cases of healthcare-associated Gram-negative bloodstream infection in 2014 and 2015. The colistin resistance rate in Klebsiella pneumoniae was 16.1%, compared with 6% in 2013. In total, 660 (42.4%) cases were fatal. The highest fatality rate was among patients with Acinetobacter baumannii bacteraemia (58%), followed by Pseudomonas aeruginosa (45%), Klebsiella pneumoniae (41%), Enterobacter cloacae (32%) and Escherichia coli (28%). On multi-variate analysis, the minimum inhibitory concentrations for carbapenems [odds ratio (OR) 1.02, 95% confidence interval (CI) 1.01-1.04; P = 0.002] and colistin (OR 1.1, 95% CI 1.03-1.17; P = 0.001) were found to be significantly associated with fatality.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Carbapenems; Colistin; Cross Infection; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies

Plasmid-borne colistin resistance mediated by mcr-1 may contribute to the dissemination of pan-resistant Gram-negative bacteria. Here, we show that mcr-1 confers resistance to colistin-induced lysis and bacterial cell death, but provides minimal protection from the ability of colistin to disrupt the Gram-negative outer membrane. Indeed, for colistin-resistant strains of Enterobacteriaceae expressing plasmid-borne mcr-1, clinically relevant concentrations of colistin potentiate the action of antibiotics that, by themselves, are not active against Gram-negative bacteria. The result is that several antibiotics, in combination with colistin, display growth-inhibition at levels below their corresponding clinical breakpoints. Furthermore, colistin and clarithromycin combination therapy displays efficacy against mcr-1-positive Klebsiella pneumoniae in murine thigh and bacteremia infection models at clinically relevant doses. Altogether, these data suggest that the use of colistin in combination with antibiotics that are typically active against Gram-positive bacteria poses a viable therapeutic alternative for highly drug-resistant Gram-negative pathogens expressing mcr-1.

Topics: Animals; Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Bacterial; Drug Therapy, Combination; Enterobacter aerogenes; Enterobacter cloacae; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Ethanolaminephosphotransferase; Klebsiella Infections; Klebsiella pneumoniae; Mice; Microbial Sensitivity Tests

Acinetobacter baumannii is a nosocomial pathogen responsible for various infections, including bloodstream infections, meningitis and ventilator-associated pneumonia. It is resistant to most antimicrobial agents, including colistin, and the development of colistin-resistant A. baumannii is of serious concern in the hospital setting. In this study, the whole-genome shotgun sequences of seven colistin-resistant A. baumannii isolates from bloodstream infections were characterised.. Colistin susceptibility testing was performed by broth microdilution. Whole genomes of all seven isolates were sequenced using an Ion Torrent™ PGM platform with 400-bp chemistry.. All seven isolates were confirmed to be resistant to colistin, with minimum inhibitory concentrations (MICs) ranging from 8μg/mL to 64μg/mL. Various antimicrobial resistance genes were present. The mcr1-5 genes were absent in all seven isolates. Chromosomal mutations that could be responsible for colistin resistance were observed. Six isolates belonged to ST848 and one isolate belonged to ST451.. Increased colistin resistance among clinical isolates of A. baumannii is alarming. Several mutations that could be responsible for colistin resistance were observed in all seven isolates. However, the significant contribution of these mutations requires further confirmation. However, genome information for these colistin-resistant A. baumannii isolates will be helpful for further comparative analysis.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Bacterial; Genome, Bacterial; Humans; Microbial Sensitivity Tests

This study aimed to determine potential host-, pathogen-, infection- and treatment-related risk factors that might predict a fulminant fatal course of bacteraemia caused by extensively drug-resistant Acinetobacter baumannii (XDR-Aba).. Eighty-seven patients with monomicrobial growth of XDR-Aba in blood cultures within a 6-year period (2011-2016) were studied. Patients were divided into three groups according to ICU outcome: Group A (n=40) consisted of patients who survived; Group B (n=10) included patients with fulminant sepsis who died early (≤48h); and Group C (n=37) included patients who died later (>48h) after the onset of bacteraemia.. Regarding patient co-morbidities, patients who died from fulminant XDR-Aba bacteraemia had a significantly higher prevalence of chronic renal failure compared with patients who survived (40.0% vs. 7.5%; P=0.029). Patients with fulminant sepsis showed more severe organ dysfunction based on SOFA score compared with survivors (10.83±2.93 vs. 6.65±3.6; P=0.013). The primary to secondary bacteraemia ratio and appropriate treatment were similar among the three outcome groups. Patients with fulminant bacteraemia displayed higher rates of colistin-, tigecycline- and pandrug-resistant strains, although not statistically significant.. Patients suffering from a fulminant course of XDR-Aba bacteraemia showed significantly higher rates of chronic renal failure and multiple organ dysfunction. Resistance patterns of XDR-Aba isolates and receipt of appropriate treatment did not affect outcomes. Further studies including larger samples of patients along with investigation of specific virulence determinants of individual Aba strains are needed.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Intensive Care Units; Kidney Failure, Chronic; Male; Middle Aged; Retrospective Studies; Risk Factors; Sepsis

Polymyxins are one of the last-line antibiotics for multidrug-resistant Acinetobacter baumannii. Reports have demonstrated the emergence of colistin heteroresistance in A. baumannii, which can complicate assessment of minimum inhibitory concentrations and promote resistance to colistin. We aimed to determine the presence of colistin heteroresistance in A. baumannii isolates and correlate the results with clinical and microbiological outcomes via a retrospective study of 24 adult patients: 12 blood and 12 invasive respiratory cultures positive for colistin-susceptible A. baumannii between 1 January 2013 and 31 July 2015. Heteroresistance testing was performed by plating a 100-μL bacterial cell suspension on Mueller-Hinton agar plates containing 0, 1, 2, and 4 μg/mL colistin, and assessing for growth at 24 and 48 h. Colistin heteroresistance was exhibited in 83% of isolates. Median age was 56 [43-65] years, 10 (42%) patients resided at a facility prior to admission, 5 (21%) had a chronic tracheostomy, 18 (75%) were in the intensive care unit at the time of culture collection, and median infection-related length of stay was 12 [7-15] days. Clinical and microbiological cures were achieved in 75% of patients. Overall infection-related mortality was 21%. Our study demonstrated a high rate of colistin heteroresistance in clinical isolates of colistin-susceptible A. baumannii, although this was not associated with suboptimal clinical outcomes due to the use of aggressive colistin dosing and combination therapy. Further studies are needed to establish the association between in vitro colistin heteroresistance and clinical and microbiological outcomes.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Cohort Studies; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Respiratory Tract Infections; Retrospective Studies

Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp) has emerged globally over the last decade as a major nosocomial pathogen that threatens patient care. These highly resistant bacteria are mostly associated with a single Kp clonal group, CG258, but the reasons for its host and hospital adaptation remain largely unknown.. We analyzed the in vivo evolution of a colistin-resistant KPC-Kp CG258 strain that contaminated a patient following an endoscopy and was responsible for a fatal bacteremia 4.5 years later. Whole-genome sequencing was performed on 17 KPC-Kp isolates from this patient; single-nucleotide polymorphisms were analyzed and their implication in antimicrobial resistance and bacterial host adaptation investigated.. The patient KPC-Kp strain diversified over 4.5 years at a rate of 7.5 substitutions per genome per year, resulting in broad phenotypic modifications. After 2 years of carriage, all isolates restored susceptibility to colistin. Higher expression of the fimbriae conferred the ability to produce more biofilm, and the isolate responsible for a bacteremia grew in human serum. The convergent mutations occurring in specific pathways, such as the respiratory chain and the cell envelope, revealed a complex long-term adaptation of KPC-Kp.. Broad genomic and phenotypic diversification and the parallel selection of pathoadaptive mutations might contribute to long-term carriage and virulence of KPC-Kp CG258 strains and to the dissemination of this clone.

Topics: Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Biofilms; Carrier State; Colistin; Drug Resistance, Bacterial; Endoscopy; Equipment Contamination; Evolution, Molecular; Fatal Outcome; Fimbriae, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Mutation; Polymorphism, Single Nucleotide; Whole Genome Sequencing

A matched 1:2 case-control study was conducted among critically ill patients in order to identify the risk factors of colistin or tigecycline-resistant carbapenemase-producing Klebsiella pneumoniae (ColR-Kp, TigR-Kp) bacteraemia. MIC to colistin and tigecycline were determined by Etest. From 224 bacteraemic patients, 46.4% and 29.5% were resistant to colistin and tigecycline, respectively. PCR revealed that 199 isolates carried the bla

Topics: Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Case-Control Studies; Colistin; Comorbidity; Critical Care; Critical Illness; Drug Resistance, Bacterial; Female; Genotype; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Molecular Epidemiology; Molecular Typing; Tigecycline

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Colistin; Conjugation, Genetic; Drug Resistance, Bacterial; Escherichia coli Proteins; Gene Transfer, Horizontal; Humans; Male; Microbial Sensitivity Tests; Polymerase Chain Reaction; Salmonella enterica; Salmonella Infections; Sequence Analysis, DNA; Serogroup; Switzerland

Amidst the ever-rising threat of antibiotics resistance, colistin, a decade-old antibiotic with lingering toxicity concern, is increasingly prescribed to treat many drug-resistant, gram-negative bacteria. With the aim of improving the safety profile while preserving the antimicrobial activity of colistin, a nanoformulation is herein developed through coacervate complexation with polyanionic peptides. Upon controlled mixing of cationic colistin with polyglutamic acids, formation of liquid coacervates was demonstrated. Subsequent stabilization by DSPE-PEG and homogenization through micro-fluidization of the liquid coacervates yielded nanoparticles 8 nm in diameter. In vitro assessment showed that the colistin antimicrobial activity against multiple drug-resistant bacterial strains was retained and, in some cases, enhanced following the nanoparticle assembly. In vivo administration in mice demonstrated improved safety of the colistin nanoparticle, which has a maximal tolerated dose of 12.5 mg/kg compared to 10 mg/kg of free colistin. Upon administration over a 7-day period, colistin nanoparticles also exhibited reduced hepatotoxicity as compared to free colistin. In mouse models of Klebsiella pneumoniae bacteremia and Acinetobacter baumannii pneumonia, treatment with colistin nanoparticles showed equivalent efficacy to free colistin. These results demonstrate coacervation-induced nanoparticle assembly as a promising approach towards improving colistin treatments against bacterial infections. STATEMENT OF SIGNIFICANCE: Improving the safety of colistin while retaining its antimicrobial activity has been a highly sought-after objective toward enhancing antibacterial treatments. Herein, we demonstrate formation of stabilized colistin nanocomplexes in the presence of anionic polypeptides and DSPE-PEG stabilizer. The nanocomplexes retain colistin's antimicrobial activity while demonstrating improved safety upon in vivo administration. The supramolecular nanoparticle assembly of colistin presents a unique approach towards designing antimicrobial nanoparticles.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Bacteremia; Colistin; Klebsiella Infections; Klebsiella pneumoniae; Mice; Mice, Inbred BALB C; Nanoparticles; Pneumonia, Bacterial

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

Host defense peptides are preferably administered as topical therapeutic agents. We have investigated whether peptide A3-APO can enter the circulation when applied to the ear skin. Efficacy of peptide monotherapy as transdermal administration option was assessed in a systemic mouse Acinetobacter baumannii model. A3-APO reduced mortality and demonstrated a statistically significant reduction of blood bacterial counts, regardless whether it was administered prior or after bacterial challenge. The peptidic metabolite of A3-APO was efficacious when applied to the ear or tail.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Cutaneous; Amino Acid Sequence; Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Arginine; Bacteremia; Bacterial Load; Carbapenems; Colistin; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Ear; Humans; Mice; Proline; Skin; Survival Analysis

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

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

Acinetobacter species are not considered skin commensals and under-treatment is an overriding concern when caring for critically-ill patients who are mostly at risk of extensively drug-resistant Acinetobacter baumannii (XDRAB) infections. Hence even a single blood culture yielding XDRAB will tend to prompt intervention. However, field observations suggest that patients with single-positive blood cultures had milder disease and were more likely to be recruited in interventional studies than those with multiple-positive blood cultures, yet no distinction is made in current clinical or trial recruitment practices. To our knowledge, this is the first study to compare the clinical characteristics and outcomes of patients with single-positive versus multiple-positive blood cultures for XDRAB. In this multicenter prospective cohort study of XDRAB bacteremic patients from July 2010 to June 2015, only patients with at least two simultaneously drawn blood cultures were included. The patients were classified as having single-positive or multiple-positive blood cultures according to the number of positive blood cultures yielding XDRAB. The primary end-point was the 28-day mortality. Of a total of 155 patients enrolled, 69 had a single-positive and 86 had multiple-positive blood cultures. Leukopenia (37.2% vs. 16.2%; P = 0.004), thrombocytopenia (56.0% vs. 26.5%; P < 0.001), higher Pitt bacteremia scores (6.6 vs. 5.5, P = 0.03) and higher 28-day mortality rates (70.9% vs. 43.5%; P = 0.001) distinguished patients with multiple-positive from those with single-positive cultures. Multivariate logistic regression showed that multi-positivity independently predicted 28-day mortality (adjusted odds ratio, 2.34; 95% confidence interval (CI), 1.03-5.28; P = 0.04) and the Cox regression confirmed that multi-positivity (adjusted hazard ratio, 1.80; 95% CI, 1.13-2.85; P = 0.01) predicted rapid mortality. Patients with multiple versus single positive blood cultures yielding XDRAB had greater morbidity and mortality. Investigators and clinicians should be aware that the blood culture positivity rate impacts outcomes of XDRAB bacteremia.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Blood Culture; Carbapenems; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Female; Humans; Intensive Care Units; Leukopenia; Microbial Sensitivity Tests; Middle Aged; Prospective Studies; Severity of Illness Index; Survival Analysis; Thrombocytopenia

In this study, we retrospectively evaluated clinical outcomes of 75 patients with dual colistin- and carbapenem-resistant Klebsiella pneumoniae bloodstream infections over a 5-year period in a single tertiary care hospital in India. We observed a high in-hospital mortality rate of 69.3%. Our findings indicate the urgent need for new antibiotics to treat these infections.

Topics: Anti-Bacterial Agents; Bacteremia; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; India; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Treatment Outcome

To determine the impact of using colistin for multidrug-resistant organisms in neonates.. This retrospective study was conducted at the Shifa International Hospital, Islamabad, Pakistan, and comprised microbiological data of babies from January 2010 to October 2012.The data was reviewed to identify the babies infected with multidrug-resistant organisms and who had received colistin therapy. SPSS 16 was used for data analysis.. Of the 30 neonates, 24(80%) were males and 6(20%) were females. Besides, 16(53.3%) neonates were preterm babies (< 37 weeks gestation). Two or more risk factors for multidrug-resistant organisms were present in 13(44%) babies. Mechanical ventilation was found in 26(87%) neonates and prior prolonged use of antibiotics in 7(23%). The commonest pathogen isolated was Acinetobacter, in 22(73%) cases. All isolates were susceptible to colistin but pan-resistant to multiple antibiotics, including cephalosporins, amikacin, meropenem and piperacillin/tazobactam. Colistin therapy was used for bacteraemia in 2(7%) cases, clinical sepsis 18(60%), pneumonia 2(7%) and tracheitis 8(26.7%). Moreover, 15(50%) neonates received both intravenous and aerosolised colistin while 9(30%) received aerosolised therapy alone.. Colistin therapy was well tolerated in neonates for the treatment of multidrug-resistant organisms.

Topics: Acinetobacter Infections; Administration, Inhalation; Administration, Intravenous; Anti-Bacterial Agents; Asphyxia Neonatorum; Bacteremia; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Infant, Newborn; Infant, Premature; Male; Neonatal Sepsis; Pneumonia, Bacterial; Respiration, Artificial; Respiratory Distress Syndrome, Newborn; Retrospective Studies; Tracheitis

We describe an IncX4 pHC891/16mcr plasmid carrying mcr-1 in a colistin-resistant and carbapenem-susceptible E. coli isolate (HC891/16), ST156, which caused a blood infection in a Brazilian patient with gallbladder adenocarcinoma.. Strain HC891/16 was subjected to whole genome sequencing using the MiSeq Platform (Illumina, Inc., USA). Assembly was performed using Mira and ABACAS.. The isolates showed resistance only to ciprofloxacin, ampicillin and cefoxitin, and whole-genome sequencing revealed the presence of aac(6')Ib-cr and blaTEM1.. Our findings warn of the possible silent dissemination of colistin resistance by carbapenem-susceptible mcr-1 producers, as colistin susceptibility is commonly tested only among carbapenem-resistant isolates.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Brazil; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Female; Humans; Microbial Sensitivity Tests; Plasmids

The objective of this study was to assess the achievement of pharmacokinetic/pharmacodynamic (PK/PD) targets of meropenem (MEM) in critically-ill patients with bloodstream infections (BSI) due to Klebsiella pneumoniae-carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) with MEM minimum inhibitory concentrations (MICs) ≥16 mg/L. Nineteen critically-ill patients with KPC-Kp BSI were given combination therapy including MEM, tigecycline, plus colistin or gentamicin (according to susceptibility testing). MEM was administered as an extended 3-hour infusion of 2 g every 8 hours, or adjusted according to renal function. MEM plasma concentrations were determined by high-performance liquid chromatography. PK/PD targets for MEM were defined as T > 40% 1×MIC and T > 40% 4×MIC. Possible synergisms between MEM and coadministered agents were assessed by time-kill assays based on plasma levels for MEM and on fixed plasma concentrations for the other agents. In none of 19 patients MEM reached any PK/PD target. The actual MEM MICs were 256, 512, and 1024 mg/L in 1, 3, and 15 isolates, respectively. However, theoretically, the PK/PD target of T > 40% 1×MIC could have been achieved in 95%, 68%, 32% and 0% of the isolates for MIC equal to 8, 16, 32, and 64 mg/L, respectively. No synergisms were observed between MEM and coadministered agents. In conclusion, high-dose MEM failed to reach PK/PD targets in 19 patients with BSI due to KPC-Kp with very high MEM MICs. On a theoretical basis, our results suggest a possible usefulness of MEM against resistant blood isolates with MICs up to 32 mg/L.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Colistin; Critical Illness; Drug Synergism; Drug Therapy, Combination; Female; Gentamicins; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Minocycline; Thienamycins; Tigecycline

Topics: Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Bacterial; Escherichia coli; Humans; Microbial Sensitivity Tests; Republic of Korea

A carbapenemase-producing colistin-resistant Klebsiella oxytoca isolate was recovered from a blood culture of a female patient without previous report of risk factors to obtain multidrug-resistant Gram-negative bacilli. A combination of biochemical and molecular methods was used to identify the resistance mechanism of this isolate. Carbapenemase production was mediated by Verona integron-encoded metallo-β-lactamase (VIM)-2. Colistin resistance was not due to plasmid- borne mcr-1 gene, but we found an integration of IS5-like sequence in the mgrB gene of K. oxytoca. This gene is known to be an important regulator of the PhoPQ two-component system, and the disruption of this gene is most likely the cause of lipid A modification resulting in colistin resistance of our isolate. To the best of our knowledge this constitutes the first report of a carbapenemase-producing K. oxytoca with colistin resistance, a case that demonstrates the limited treatment options for infections with multidrug-resistant organisms.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Blood; Blood Culture; Carbapenems; Colistin; Drug Resistance, Bacterial; Female; Humans; Klebsiella Infections; Klebsiella oxytoca; Membrane Proteins; Mutagenesis, Insertional; Plasmids

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

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

The increasing prevalence of multidrug-resistant (MDR) nosocomial infections accounts for increased morbidity and mortality of such infections. Infections with MDR Gram-negative isolates are frequently treated with colistin. Based on recent pharmacokinetic studies, current colistin dosing regimens may result in a prolonged time to therapeutic concentrations, leading to suboptimal and delayed effective treatment. In addition, studies have demonstrated an association between an increased colistin dose and improved clinical outcomes. However, the specific dose at which these outcomes are observed is unknown and warrants further investigation. This retrospective study utilized classification and regression tree (CART) analysis to determine the dose of colistin most predictive of global cure at day 7 of therapy. Patients were assigned to high- and low-dose cohorts based on the CART-established breakpoint. The secondary outcomes included microbiologic outcomes, clinical cure, global cure, lengths of intensive care unit (ICU) and hospital stays, and 7- and 28-day mortalities. Additionally, safety outcomes focused on the incidence of nephrotoxicity associated with high-dose colistin therapy. The CART-established breakpoint for high-dose colistin was determined to be >4.4 mg/kg of body weight/day, based on ideal body weight. This study evaluated 127 patients; 45 (35%) received high-dose colistin, and 82 (65%) received low-dose colistin. High-dose colistin was associated with day 7 global cure (40% versus 19.5%; P = 0.013) in bivariate and multivariate analyses (odds ratio [OR] = 3.40; 95% confidence interval [CI], 1.37 to 8.45; P = 0.008). High-dose colistin therapy was also associated with day 7 clinical cure, microbiologic success, and mortality but not with the development of acute kidney injury. We concluded that high-dose colistin (>4.4 mg/kg/day) is independently associated with day 7 global cure.

Topics: Acute Kidney Injury; Aged; Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; Carbapenems; Colistin; Drug Administration Schedule; Drug Dosage Calculations; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Intensive Care Units; Length of Stay; Male; Microbial Sensitivity Tests; Middle Aged; Multivariate Analysis; Retrospective Studies; Survival Analysis; Treatment Outcome

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Male; Middle Aged; Practice Guidelines as Topic; Tertiary Care Centers

Topics: Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Ceftriaxone; Colistin; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Humans; Male; Middle Aged; Plasmids

In this study, we sought to evaluate the pharmacokinetics of colistin after intravenous administration of colistimethate sodium (CMS) in the critically ill neonates with Gram-negative bacterial infections. A single intravenous dose of CMS [approximately 150,000 IU/kg, equivalent to 5 mg/kg colistin base activity (CBA)] was administered to 7 critically ill neonates. Mean (±SD) maximum plasma colistin concentration and area under the time-concentration curve from 0 to infinity were 3.0 ± 0.7 µg/mL and 25.3 ± 10.4 µg·h/mL, respectively. Time to maximum concentration, half-life, apparent volume of distribution and clearance were 1.3 ± 0.9 hours, 9.0 ± 6.5 hours, 7.7 ± 9.3 L/kg and 0.6 ± 0.3 L/h/kg, respectively. After a dose regimen of 5 mg/kg CBA every 24 hours, the average concentration expected at steady state is 1.1 ± 0.4 µg/mL. In critically ill neonates, a single intravenous dose of 5 mg CBA/kg (approximately 150,000 IU/kg of CMS) resulted in suboptimal plasma concentrations of colistin. According to our pharmacokinetics data, the dosage of CMS currently used in critically ill neonates is insufficient.

Topics: Administration, Intravenous; Anti-Bacterial Agents; Bacteremia; Colistin; Critical Illness; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Pneumonia, Bacterial; Prospective Studies

Topics: Anti-Bacterial Agents; Bacteremia; Bacteriological Techniques; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Mass Screening; Plasmids

Acinetobacter baumannii strains, are opportunistic pathogens that cause severe nosocomial infections that are difficult to treat due to development of resistance to multiple antibiotics. As the antibiotic choices to be used in treatment are limited, combinations of a variety of antibiotics are used. The aims of this study were to identify the minimal inhibitory concentration (MIC) values of colistin and sulbactam against A.baumannii isolates and to determine the in vitro activity of colistin-sulbactam combination. A total of 50 A.baumannii strains isolated from different clinical specimens (32 tracheal aspirates, 10 blood, 6 urine and 2 wound samples) were included in the study. The identification of bacteria was performed by traditional methods and Vitek-2 (BioMerieux, France) automated system. Antibiotic susceptibilities were detected by Mueller-Hinton agar disk diffusion method and Vitek-2 automated system and the results were interpreted according to the CLSI standards. MIC values of colistin and sulbactam against A.baumannii strains and in vitro interactions of colistin-sulbactam combinations were determined with the E-test (BioMerieux, France). Fractional inhibitory concentration (FIC) index was used for the detection of efficacy of drug combinations. The presence of oxacillinase and metallo-beta-lactamase (MBL) genes that lead carbapenem resistance was investigated by polymerase chain reaction (PCR), and pulsed-field gel electrophoresis (PFGE) was performed for the determination of clonal relationship. In our study, all strains (100%) were detected as susceptible to colistin, 48 (96%) to trimethoprim/sulphamethoxazole and 18 to (36%) tigecyclin; however all of them were resistant to the other studied antibiotics, including sulbactam and carbapenem. When the colistin-sulbactam combination was assessed according to FIC index, all strains were found to have antagonistic effect. All of the carbapenem-resistant strains were positive for OXA-51 and OXA-23, and 3 (6%) were positive for OXA-24. Among MBLs, OXA-58, OXA-48, IPM, SPM, SIM, GIM, VIM and NDM-1 genes were not detected. In the evaluation of PFGE results it was found that the clonal distribution of the strains, except one, were all pulsotype A. In the assessment of in vitro efficacy of the colistin-sulbactam combination against A.baumannii strains with multidrug resistance, antagonistic effect was observed in all strains. In the resistance and clonal analysis it was determined that the strains bel

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; Bacteriuria; beta-Lactamases; Carbapenems; Colistin; Drug Combinations; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Humans; Microbial Sensitivity Tests; Polymerase Chain Reaction; Sulbactam; Trachea; Wound Infection

Stenotrophomonas maltophilia is an emerging multidrug-resistant (MDR) opportunistic pathogen for which new antibiotic options are urgently needed. We report our clinical experience treating a 19-year-old renal transplant recipient who developed prolonged bacteremia due to metallo-β-lactamase-producing S. maltophilia refractory to conventional treatment. The infection recurred despite a prolonged course of colistimethate sodium (colistin) but resolved with the use of a novel drug combination with clinical efficacy against the patient's S. maltophilia isolate.

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Aztreonam; Bacteremia; beta-Lactamases; Ceftazidime; Colistin; Drug Combinations; Drug Resistance, Multiple, Bacterial; Drug Substitution; Gene Expression; Gram-Negative Bacterial Infections; Humans; Kidney Transplantation; Male; Polycystic Kidney Diseases; Stenotrophomonas maltophilia; Young Adult

Emerging resistance to colistin in clinical Acinetobacter baumannii isolates is of growing concern. Since current treatment options for these strains are extremely limited, we investigated the in vitro activities of various antimicrobial combinations against colistin-resistant A. baumannii Nine clinical isolates (8 from bacteremia cases and 1 from a pneumonia case) of colistin-resistant A. baumannii were collected in Asan Medical Center, Seoul, South Korea, between January 2010 and December 2012. To screen for potential synergistic effects, multiple combinations of two antimicrobials among 12 commercially available agents were tested using the multiple-combination bactericidal test (MCBT). Checkerboard tests were performed to validate these results. Among the 9 colistin-resistant strains, 6 were pandrug resistant and 3 were extensively drug resistant. With MCBT, the most effective combinations were colistin-rifampin and colistin-teicoplanin; both combinations showed synergistic effect against 8 of 9 strains. Colistin-aztreonam, colistin-meropenem, and colistin-vancomycin combinations showed synergy against seven strains. Colistin was the most common constituent of antimicrobial combinations that were active against colistin-resistant A. baumannii Checkerboard tests were then conducted in colistin-based combinations. Notably, colistin-rifampin showed synergism against all nine strains (100%). Both colistin-vancomycin and colistin-teicoplanin showed either synergy or partial synergy. Colistin combined with another β-lactam agent (aztreonam, ceftazidime, or meropenem) showed a relatively moderate effect. Colistin combined with ampicillin-sulbactam, tigecycline, amikacin, azithromycin, or trimethoprim-sulfamethoxazole demonstrated limited synergism. Using MCBT and checkerboard tests, we found that only colistin-based combinations, particularly those with rifampin, glycopeptides, or β-lactams, may confer therapeutic benefits against colistin-resistant A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Aztreonam; Bacteremia; Ceftazidime; Colistin; Drug Combinations; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Meropenem; Microbial Sensitivity Tests; Pneumonia, Bacterial; Retrospective Studies; Rifampin; Teicoplanin; Thienamycins; Vancomycin

Topics: Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Pseudomonas aeruginosa; Pseudomonas Infections

Treatment failures of a carbapenem-colistin regimen among patients with bacteremia due to sequence type 258 (ST258), KPC-2-producing Klebsiella pneumoniae were significantly more likely if both agents were inactive in vitro, as defined by a colistin MIC of >2 μg/ml and the presence of either a major ompK36 porin mutation (guanine and alanine insertions at amino acids 134 and 135 [ins aa 134-135 GD], IS5 promoter insertion [P = 0.007]) or a doripenem MIC of >8 μg/ml (P = 0.01). Major ompK36 mutations among KPC-K. pneumoniae strains are important determinants of carbapenem-colistin responses in vitro and in vivo.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Doripenem; Drug Therapy, Combination; Female; Genotype; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Porins; Retrospective Studies

Multidrug-resistant Acinetobacter baumannii (MAB) is an important nosocomial pathogen.. To analyze the risk factors for acquiring MAB, and the clinical and microbiological characteristics of MAB bacteremia (MABB) in children.. Control-case study 2005-2008. Demographic and clinical data from all MABB and from non-multiresistant gram-negative bacteremias were recorded. Identification at species level, antimicrobial susceptibility tests, time-kill studies and clonally relationships were performed. Stata 8.0 was used for data analysis.. A total of 50 MABB and 100 controls were included. Ninety four percent of patients acquired MAB in ICU and the 88% had underlying diseases. All patients had invasive procedures previous to MABB. The median of hospitalization stay previous to MABB was different in cases than in controls (16 vs 7 days, p < 0.001). Five clones were detected among the MABB. Time-killing curves showed bactericidal activity of ampicillin/sulbactam plus gentamicin and polymixin B. Three patients with MAB died. In a multivariate analysis final predictors of MABB were: previous use of broad-spectrum antibiotics [OR: 7,0; IC 95% 1,93-25,0; p: 0,003] and mechanical ventilation [OR: 4,19; IC 95% 1,66-10,0; p: 0,002].. MABB were detected in patients with underlying conditions, invasive procedures and prolonged hospitalization. Predictors of MABB were mechanical previous use of broad-spectrum antibiotics and mechanical ventilation.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Bacteremia; Case-Control Studies; Catheterization, Central Venous; Child; Child, Preschool; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Infant; Intensive Care Units, Pediatric; Length of Stay; Male; Microbial Sensitivity Tests; Respiration, Artificial; Retrospective Studies; Risk Factors

The clinical characteristics of patients with colistin-resistant Acinetobacter baumannii bacteraemia have been documented, but those of patients with bacteraemia caused by other Acinetobacter species remain unknown. Previous exposure to colistin has been shown to be associated with the emergence of colistin resistance, but may be not the only predisposing factor. In the current study, we highlight the risk and outcome of patients without previous exposure to colistin who acquired colistin-resistant Acinetobacter nosocomialis (ColRAN) bacteraemia. This 11-year single-centre retrospective study analysed 58 patients with ColRAN bacteraemia and 213 patients with colistin-susceptible A. nosocomialis (ColSAN) bacteraemia. Antimicrobial susceptibilities were determined with an agar dilution method. The clonal relationship of ColRAN isolates was determined with pulsed-field gel electrophoresis. A conjugation mating-out assay was conducted to delineate the potential transfer of colistin resistance genes. Multivariable analysis was performed to evaluate the risk factors for ColRAN bacteraemia. Chronic obstructive pulmonary disease (COPD) was independently associated with ColRAN bacteraemia (OR 3.04; 95% CI 1.45-6.37; p 0.003). Patients with ColRAN bacteraemia had higher APACHE II scores, but the two groups showed no significant differences in 14-day mortality (10.3% vs. 10.3%) or 28-day mortality (15.5% vs. 15.0%). ColRAN isolates had greater resistance than ColSAN isolates to all antimicrobial agents except for ciprofloxacin (0% vs. 6.6%). There were 16 different ColRAN pulsotypes, and two major clones were found. Colistin resistance did not transfer to colistin-susceptible A. baumannii or A. nosocomialis. These results show that COPD is an independent risk factor for acquisition of ColRAN bacteraemia. The mortality rates were similar between patients with ColRAN and ColSAN bacteraemia.

Topics: Acinetobacter; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Colistin; Conjugation, Genetic; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Gene Transfer, Horizontal; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Molecular Typing; Retrospective Studies; Risk Factors; Survival Analysis; Treatment Outcome; Young Adult

A 56-year-old woman with systemic lupus erythematosus had bacteremia due to multidrug-resistant Pseudomonas aeruginosa (MDRP). She was initially treated with imipenem-cilastatin, tobramycin, and aztreonam; however, MDRP was still detected intermittently in her plasma. Multidrug-susceptibility tests demonstrated that MDRP was susceptible only to colistin. Therefore, in addition to these antibiotics, the administration of intravenous colistin methanesulfonate, a prodrug formula of colistin, was started at a daily dose of 2.5 mg/kg (as colistin base activity). The initial dose setting was based on the patient's renal function (baseline creatinine clearance=32.7 mL/min). After initiating colistin, the patient's C-reactive protein levels gradually decreased. Blood cultures showed no evidence of MDRP on days 8, 14, and 22 after colistin initiation. However, the patient's renal function went from bad to worse owing to septic shock induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. A few days later, the trough plasma levels of colistin were 7.88 mg/L, which appeared to be higher than expected. After decreasing the colistin dose, the patient's renal function gradually improved. On the final day of colistin treatment, the plasma levels decreased to 0.60 mg/L. MDRP could not be detected in blood culture after colistin treatment. Therefore, we successfully treated a case of bloodstream infection due to MDRP by therapeutic drug monitoring (TDM) of colistin. It is suggested that the monitoring of blood colistin levels by liquid chromatography-tandem mass spectrometry can contribute to safer, more effective antimicrobial therapy of MDRP because TDM facilitates quick decisions on dose adjustments.

Topics: Anti-Bacterial Agents; Bacteremia; Colistin; Drug Monitoring; Drug Resistance, Multiple, Bacterial; Female; Humans; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Treatment Outcome

We describe a large hospital outbreak (93 bloodstream infections) of colistin-resistant Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae isolates which was mirrored by increased colistin consumption. The outbreak was mostly traced to the clonal expansion of an mgrB deletion mutant of an ST512 strain that produced KPC-3.

Topics: Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Colistin; Cross Infection; Disease Outbreaks; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Genotype; Humans; Klebsiella Infections; Klebsiella pneumoniae; Molecular Typing; Sequence Deletion

The increasing prevalence of colistin resistance (ColR) Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (Kp) is a matter of concern because of its unfavourable impact on mortality of KPC-Kp bloodstream infections (BSI) and the shortage of alternative therapeutic options. A matched case-control-control analysis was conducted. The primary study end point was to assess risk factors for ColR KPC-Kp BSI. The secondary end point was to describe mortality and clinical characteristics of these infections. To assess risk factors for ColR, 142 patients with ColR KPC-Kp BSI were compared to two controls groups: 284 controls without infections caused by KPC-Kp (control group A) and 284 controls with colistin-susceptible (ColS) KPC-Kp BSI (control group B). In the first multivariate analysis (cases vs. group A), previous colistin therapy, previous KPC-Kp colonization, ≥3 previous hospitalizations, Charlson score ≥3 and neutropenia were found to be associated with the development of ColR KPC-Kp BSI. In the second multivariate analysis (cases vs. group B), only previous colistin therapy, previous KPC-Kp colonization and Charlson score ≥3 were associated with ColR. Overall, ColR among KPC-Kp blood isolates increased more than threefold during the 4.5-year study period, and 30-day mortality of ColR KPC-Kp BSI was as high as 51%. Strict rules for the use of colistin are mandatory to staunch the dissemination of ColR in KPC-Kp-endemic hospitals.

Topics: Aged; Bacteremia; Case-Control Studies; Colistin; Drug Resistance, Multiple, Bacterial; Female; Hospitalization; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Risk Factors

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

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

New antibiotic options are urgently needed for the treatment of carbapenem-resistant Enterobacteriaceae infections. We report a 64-year-old female with prolonged hospitalization following an intestinal transplant who developed refractory bacteremia due to a serine carbapenemase-producing pandrug-resistant isolate of Klebsiella pneumoniae. After failing multiple antimicrobial regimens, the patient was successfully treated.

Topics: Anti-Bacterial Agents; Antiviral Agents; Azabicyclo Compounds; Bacteremia; Bacterial Proteins; beta-Lactamases; Carbapenems; Ceftazidime; Colectomy; Colistin; Drug Combinations; Drug Resistance, Multiple, Bacterial; Female; Ganciclovir; Humans; Immunosuppressive Agents; Intestine, Small; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Middle Aged; Minocycline; Thienamycins; Tigecycline; Trimethoprim, Sulfamethoxazole Drug Combination; Valganciclovir

Acinetobacter baumannii is an important hospital-acquired pathogen in healthcare facilities that frequently causes bacteraemia and ventilator-associated pneumonia in intensive care units. Acinetobacter baumannii can be isolated from various sites in the hospital environment like medical equipment, bed linen, medical personnel and indwelling catheters. It is difficult to treat A. baumannii infections because of their highly resistant antimicrobial profiles. The purpose of this study was to determine the prevalence of β-lactamase genes in multidrug-resistant (MDR) clinical A. baumannii isolates using Multiplex-PCR (M-PCR) assays.. One hundred MDR A. baumannii isolates were collected from the diagnostic division of the Department of Medical Microbiology after routine analysis of the submitted specimens. All collected isolates were identified and tested for susceptibility using the VITEK 2® system (bioMérieux, France). Six isolates were excluded from this study because the isolates were incorrectly identified as A. baumannii with the VITEK 2® system (bioMérieux, France). Molecular tests, namely M-PCR assays, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) were performed. MLST analyses were performed on representative isolates from the four major pulsotypes (≥5 isolates with 80 % similarity) and selective isolates from each minor pulsotype.. All the A. baumannii isolates showed 100 % resistance to ampicillin, amoxicillin, cefuroxime, cefuroximine axetil, cefoxitin, cefotaxime and nitrofurantoin. Seven percent of the isolates were resistant to amikacin. Two percent of the isolates were classified as having intermediate susceptibility to tigecycline. A. baumannii isolates showed an antibiotic resistance profile of 67 % and higher to antibiotics, such as ceftazidime, cefepime, imipenem, meropenem, gentamicin, ciprofloxacin and trimethoprim/sulfamethoxazole. None of the isolates were resistant to colistin. The M-PCR assays showed that 99 % of the isolates contained the OXA-51 gene and 77 % contained the OXA-23 gene. None of the isolates contained the GES, GIM, IMP, KPC, NDM, OXA-24, OXA-58, PER, SIM, SPM, VEB and VIM genes. Representative A. baumannii isolates were grouped into five existing sequence types (ST): ST106, ST258, ST339, ST502, ST758 and ST848. Isolates belonging to the pan-European clonal lineages I and II (EUI and EUII) were identified.. The high prevalence of MDR A. baumannii isolates has a severe impact on available treatment choices and this in return impacts on treatment outcomes in the studied healthcare facilities. The most dominant ST among the collected isolates was ST758, member of the EUI group. The presence of the OXA-23 gene was not restricted to a specific ST. Continuous research and surveillance is necessary to monitor the circulating β-lactamase genes in clinical settings to guide infection control policies in order to try and curb the spread of this bacterium.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; beta-Lactamases; Child; Child, Preschool; Colistin; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Humans; Infant; Infant, Newborn; Intensive Care Units; Middle Aged; Multilocus Sequence Typing; Multiplex Polymerase Chain Reaction; South Africa; Young Adult

Carbapenem resistance among the Enterobacteriaceae is a serious healthcare challenge. bla IMI is a carbapenemase gene mediating resistance to carbapenems but has not been commonly found. A bla IMI-carrying Enterobacter cloacae, which was also resistant to colistin, is reported here.. E. cloacae strain WCHECl-1060 was recovered from a blood sample of a leukemia patient, who was not previously exposed to colistin. Strain WCHECl-1060 belongs to a new sequence type, ST410, and was resistant to carbapenems and colistin but was susceptible to third-generation cephalosporins. A new allelic variant of bla IMI-1, which has two silent mutations compared to the original bla IMI-1 variant, was found in strain WCHECl-1060. Conjugation and transformation experiments failed to transfer bla IMI-1, suggesting a likely chromosome origin.. To our knowledge, this is the first report of an IMI-1 carbapenemase-producing colistin-resistant E. cloacae in China. Microbiological laboratories should be aware of the unusual carbapenem-resistant but third-generation cephalosporin-susceptible profiles of these IMI-producing isolates. The trend of colistin resistance among the Enterobacteriaceae should be also monitored.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Carbapenems; China; Colistin; Conjugation, Genetic; DNA, Bacterial; Drug Resistance, Bacterial; Enterobacter cloacae; Enterobacteriaceae Infections; Humans; Leukemia; Male; Molecular Sequence Data; Molecular Typing; Sequence Analysis, DNA

Infections caused by carbapenem-resistant bacteria constitute a major challenge for current medical practice.. To describe treatment and outcome of carbapenem-resistant Gram-negative bacilli (GNB) blood-stream infection (BSI) caused by these organisms at a tertiary care hospital in Mumbai.. Carbapenem-resistant isolates from blood cultures were collected from January 2013 to April 2013. Identification and antimicrobial susceptibility testing were performed using Vitek 2 analyzer (Biomerieux Ltd.). Carbapenemase production was detected by modified Hodge's test (MHT). Patient's medical history, treatment and co-morbid conditions were noted. Outcomes of BSIs were evaluated.. Forty-two isolates of carbapenem-resistant GNB isolated from BSIs were Enterobacteriaceae spp. (19), Acinetobacter baumannii (15), and Pseudomonas aeruginosa (8). Colistin had maximum in vitro activity with 97% against Enterobacteriaceae, 100% against Acinetobacter, and 100% activity against Pseudomonas aeruginosa isolates. Positivity of MHT was 92.9%. Outcome of colistin mono and combination therapy was comparable with 83% and 79%, respectively. Outcome of colistin and carbapenem combination therapy was found to be 100 percent.. High incidences of bacteremia by carbapenem-resistant GNB including Enterobacteriaceae is a worrisome trend. Treatment options are compromised and only available option is colistin which has its own limitation. Colistin monotherapy may be non-inferior compared to combination therapy for treating BSIs caused by isolates with minimum inhibitory concentration (MIC) for colistin as ≤0.5 mg/l. Combined use of the colistin and carbapenem may provide good therapeutic options for BSI caused by carbapenem-resistant GNB and warrants further investigations.

Topics: Acinetobacter baumannii; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; Carbapenems; Child; Child, Preschool; Colistin; Enterobacteriaceae; Female; Gram-Negative Bacterial Infections; Humans; India; Infant; Male; Microbial Sensitivity Tests; Middle Aged; Pseudomonas aeruginosa; Tertiary Care Centers; Treatment Outcome; Young Adult

Colistin resistance remains rare among clinical isolates of Acinetobacter species. We noted the emergence of colistin-resistant bloodstream isolates of the Acinetobacter genomic species (GS) 13BJ/14TU from patients at a university hospital between 2003 and 2011. We report here, for the first time, the microbiological and molecular characteristics of these isolates, with clinical features of Acinetobacter GS 13BJ/14TU bacteremia. All 11 available patient isolates were correctly identified as Acinetobacter GS 13BJ/14TU using partial rpoB gene sequencing but were misidentified using the phenotypic methods Vitek 2 (mostly as Acinetobacter baumannii), MicroScan (mostly as A. baumannii/Acinetobacter haemolyticus), and the API 20 NE system (all as A. haemolyticus). Most isolates were susceptible to commonly used antibiotics, including carbapenems, but all were resistant to colistin, for which it is unknown whether the resistance is acquired or intrinsic. However, the fact that none of the patients had a history of colistin therapy strongly suggests that Acinetobacter GS 13BJ/14TU is innately resistant to colistin. The phylogenetic tree of multilocus sequence typing (MLST) showed that all 11 isolates formed a separate cluster from other Acinetobacter species and yielded five sequence types. However, pulsed-field gel electrophoresis (PFGE) revealed 11 distinct patterns, suggesting that the bacteremia had occurred sporadically. Four patients showed persistent bacteremia (6 to 17 days), and all 11 patients had excellent outcomes with cleared bacteremia, suggesting that patients with Acinetobacter GS 13BJ/14TU-associated bacteremia show a favorable outcome. These results emphasize the importance of precise species identification, especially regarding colistin resistance in Acinetobacter species. In addition, MLST offers another approach to the identification of Acinetobacter GS 13BJ/14TU, whereas PFGE is useful for genotyping for this species.

Topics: Acinetobacter; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Bacterial Typing Techniques; Child; Colistin; DNA-Directed RNA Polymerases; DNA, Bacterial; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Genotype; Hospitals, University; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Molecular Sequence Data; Multilocus Sequence Typing

The purpose of this investigation was to compare the efficacy of colistin-based therapies in extremely drug-resistant Acinetobacter spp. bloodstream infections (XDR-ABSI). A retrospective study was conducted in 27 tertiary-care centers from January 2009 to August 2012. The primary end-point was 14-day survival, and the secondary end-points were clinical and microbiological outcomes. Thirty-six and 214 patients [102 (47.7%): colistin-carbapenem (CC), 69 (32.2%): colistin-sulbactam (CS), and 43 (20.1%: tigecycline): colistin with other agent (CO)] received colistin monotherapy and colistin-based combinations, respectively. Rates of complete response/cure and 14-day survival were relatively higher, and microbiological eradication was significantly higher in the combination group. Also, the in-hospital mortality rate was significantly lower in the combination group. No significant difference was found in the clinical (p = 0.97) and microbiological (p = 0.92) outcomes and 14-day survival rates (p = 0.79) between the three combination groups. Neither the timing of initial effective treatment nor the presence of any concomitant infection was significant between the three groups (p > 0.05) and also for 14-day survival (p > 0.05). Higher Pitt bacteremia score (PBS), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Charlson comorbidity index (CCI), and prolonged hospital and intensive care unit (ICU) stay before XDR-ABSI were significant risk factors for 14-day mortality (p = 0.02, p = 0.0001, p = 0.0001, p = 0.02, and p = 0.01, respectively). In the multivariable analysis, PBS, age, and duration of ICU stay were independent risk factors for 14-day mortality (p < 0.0001, p < 0.0001, and p = 0.001, respectively). Colistin-based combination therapy resulted in significantly higher microbiological eradication rates, relatively higher cure and 14-day survival rates, and lower in-hospital mortality compared to colistin monotherapy. CC, CS, and CO combinations for XDR-ABSI did not reveal significant differences with respect to 14-day survival and clinical or microbiological outcome before and after propensity score matching (PSM). PBS, age, and length of ICU stay were independent risk factors for 14-day mortality.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Bacteremia; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Length of Stay; Male; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Risk Factors; Sulbactam; Treatment Outcome

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Cefepime; Cephalosporins; Ciprofloxacin; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Immunocompromised Host; Meropenem; Pseudomonas aeruginosa; Pseudomonas Infections; Thienamycins; Tobramycin; Treatment Failure

Combination therapy is recommended for the treatment of KPC-producing Klebsiella pneumoniae (KPC-Kp), but the optimal regimen for colistin-resistant strains is unknown. We compared the synergistic activity and post-antibiotic effect (PAE) of colistin in combination with other antimicrobials against colistin-susceptible and -resistant KPC-Kp bloodstream isolates.. The genotypes of nine colistin-susceptible and eight colistin-resistant KPC-Kp bloodstream isolates were analysed using PCR and amplicon sequencing. Combinations of colistin, meropenem, tigecycline, rifampicin and teicoplanin were then screened using the Etest, a chequerboard assay and time-kill studies. Synergistic combinations were also analysed with respect to the PAE in time-kill curves and the PAE at clinically achievable concentrations.. Insertional inactivation of the PhoQ/PhoB two-component regulatory system by mgrB-IS5 was identified in 6/8 (75%) colistin-resistant KPC-Kp. Colistin/rifampicin combinations resulted in no interactions [fractional inhibitory concentration (FIC) indices 1.5-2] for colistin-susceptible strains, but were uniformly synergistic (FIC indices 0.1-0.4) against colistin-resistant KPC-Kp. Time-kill kinetic analysis, at clinically achievable fixed concentrations of rifampicin and colistin, confirmed synergy and produced persistent growth inhibition (3 h) of colistin-resistant KPC-Kp strains exposed to colistin/rifampicin or colistin/rifampicin/tigecycline combinations.. Combinations of colistin plus rifampicin, and less frequently tigecycline, exhibited synergistic activity in vitro against colistin-resistant KPC-Kp strains.

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Colistin; DNA, Bacterial; Drug Resistance, Bacterial; Drug Synergism; Genotype; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Minocycline; Polymerase Chain Reaction; Rifampin; Sequence Analysis, DNA; Tigecycline

Blood stream infections (BSIs) due to carbapenem-resistant Enterobacteriaceae (CRE) are associated with high hospital mortality rates and present a tremendous challenge to clinicians. The optimal treatment remains undefined. We aimed to investigate the risk factors for mortality and the correlation between different treatment modalities and outcomes.. The clinical characteristics and treatment outcomes of a cohort of 36 patients with BSIs due to CRE were investigated and a retrospective nested case-control study of surviving and non-surviving patients was conducted.. Fifty percent of the cases were male and the mean patient age was 54.9 ± 15.8 years. Klebsiella pneumoniae was the etiological agent in 26 cases (72.2%), Escherichia coli in eight (22.2%), and Enterobacter aerogenes in two (5.5%). All strains were phenotypically positive for carbapenemase activity and all except two (one E. coli and one K. pneumoniae) yielded both blaOXA-48 carbapenemases and blaCTX-M-type extended-spectrum beta-lactamases (ESBLs) in PCR products. The 14-day, 28-day, and all-cause in-hospital mortality rates were 41.6%, 50%, and 58.3%, respectively. The median time to death was 8 days (range 2-52 days). No significant differences were observed between survivors and non-survivors in terms of baseline characteristics, comorbid conditions, etiologies, or sources of bacteremia, however hematological malignancies (p=0.015) and prolonged neutropenia (p=0.044) were more common in non-survivors. Microbiological eradication and clinical response within 7 days were two major determinants of 28-day attributable mortality (p=0.001 and p=0.001, adjusted r(2)=0.845). Colistin-based dual combinations, and preferably triple combinations, were associated with significantly better outcomes when compared to non-colistin-based regimens (p<0.001). Time to active treatment had a significant effect on the course of infection (p=0.014).. Earlier active treatment with colistin based regimens and microbiological and clinical response within 7 days are major predictors of survival in cases of BSIs due to CRE. Rectal screening offers the advantage of earlier recognition and prompt empirical treatment.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Carbapenems; Case-Control Studies; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Female; Hospital Mortality; Humans; Klebsiella pneumoniae; Male; Middle Aged; Retrospective Studies; Risk Factors; Treatment Outcome

We evaluated three commercial colistin susceptibility testing methods using 213 bloodstream Acinetobacter isolates identified by gene sequencing. Compared to the agar dilution reference method, excellent categorical agreements (both 99.1%) were observed using Vitek 2 and Etest, compared to 87.3% (95.7% for Acinetobacter baumannii and 80.7% for non-baumannii Acinetobacter isolates) using MicroScan.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; Colistin; Hospitals, University; Humans; Microbial Sensitivity Tests; Republic of Korea

Topics: Aged; Anti-Bacterial Agents; Bacteremia; beta-Lactams; Carbapenems; Colistin; Doripenem; Drug Resistance, Bacterial; Drug Therapy, Combination; Ertapenem; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Pneumonia, Ventilator-Associated; Treatment Outcome

Selective decontamination of the digestive tract (SDD) selectively eradicates aerobic Gram-negative bacteria (AGNB) by the enteral administration of oral nonabsorbable antimicrobial agents, i.e., colistin and tobramycin. We retrospectively investigated the impact of SDD, applied for 5 years as part of an infection control program for the control of an outbreak with extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae in an intensive care unit (ICU), on resistance among AGNB. Colistin MICs were determined on stored ESBL-producing K. pneumoniae isolates using the Etest. The occurrence of both tobramycin resistance among pathogens intrinsically resistant to colistin (CIR) and bacteremia caused by ESBL-producing K. pneumoniae and CIR were investigated. Of the 134 retested ESBL-producing K. pneumoniae isolates, 28 were isolated before SDD was started, and all had MICs of <1.5 mg/liter. For the remaining 106 isolated after starting SDD, MICs ranged between 0.5 and 24 mg/liter. Tobramycin-resistant CIR isolates were found sporadically before the introduction of SDD, but their prevalence increased immediately afterward. Segmented regression analysis showed a highly significant relationship between SDD and resistance to tobramycin. Five patients were identified with bacteremia caused by ESBL-producing K. pneumoniae before SDD and 9 patients thereafter. No bacteremia caused by CIR was found before SDD, but its occurrence increased to 26 after the introduction of SDD. In conclusion, colistin resistance among ESBL-producing K. pneumoniae isolates emerged rapidly after SDD. In addition, both the occurrence and the proportion of tobramycin resistance among CIR increased under the use of SDD. SDD should not be applied in outbreak settings when resistant bacteria are prevalent.

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Colistin; Cross Infection; Decontamination; Disease Outbreaks; Drug Resistance, Bacterial; Gastrointestinal Tract; Humans; Infection Control; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Retrospective Studies; Tobramycin

Colistin is increasingly used as the last-resort treatment option against infections caused by multidrug-resistant (MDR) Gram-negative pathogens, but its nephrotoxicity is of concern, especially in severely ill patients. The aim of this study was to analyze the toxicity of colistin therapy in adults and children with hematological malignancies (HM) and hematopoietic stem cell transplantation (HSCT) recipients.. Data on HSCT recipients and HM patients, treated with intravenous colistin (2.5-5 mg/kg/day in children and 3-6 million international units (IU) in adults, adjusted to renal function) during the period 2008-2011 in our center, were retrospectively collected and analyzed. Nephrotoxicity was defined according to the RIFLE criteria (Risk, Injury, Failure, Loss, and End-stage kidney disease).. Twenty-nine children and adults received 38 courses of intravenous colistin (2.5-5 mg/kg/day in children and 3-6 × 10(6) IU in adults, adjusted to renal function) [allogeneic HSCT (22 courses) and HM (16 courses)] for 3-28 days (median 10 days) for empirical therapy for nosocomial clinical sepsis (28) or local infection (6), and bacteremia with MDR Gram-negative rods (4). Nephrotoxicity was observed at the end of 4 (10.5%) courses. In 32 (84%) courses, nephrotoxic medications were concomitantly administered. Two patients had convulsions, probably unrelated to colistin. Seven patients (18%) died while on colistin therapy. No death was attributed to an adverse effect of colistin.. Treatment with intravenous colistin, with dosage adjusted to renal function, was relatively safe for HM/HSCT patients, even with concomitantly administered nephrotoxic medications. Concern about nephrotoxicity should not justify a delay in initiating empirical colistin treatment in situations where infection with MDR Gram-negative rods is likely.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacteremia; Child; Child, Preschool; Colistin; Female; Gram-Negative Bacterial Infections; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Infant; Male; Middle Aged; Retrospective Studies; Treatment Outcome

Pseudomonas aeruginosa and Acinetobcter spp. are important nosocomial pathogens and carbapenem resistance is an emerging threat. Therapeutic options for infections with these isolates include colistin. This study was conducted to determine the prevalence of carbapenem resistance in P. aeruginosa and Acinetobacter spp. bloodstream isolates, phenotypically characterize the resistance mechanisms and evaluate the in vitro activity of colistin.. Consecutive 145 (95 P.aeruginosa and 50 Acinetobacter spp.) non-repeat isolates were included. Antibiotic susceptibility testing was performed per CLSI guidelines. MIC for carbapenems and colistin was performed using Etest. Isolates showing reduced susceptibility or resistance to the carbapenems were tested for metallo-β-lactamase (MBL) production using imipenem-EDTA combined disk and MBL Etest.. Carbapenem resistance was observed in 40% P. aeruginosa and 66.0% Acinetobacter spp. Carbapenem-resistant (CA-R) isolates were significantly (p <0.05) more frequently resistant to the other antibiotics than carbapenem-susceptible isolates. Approximately half of the CA-R strains were multidrug-resistant, and 3.1-5.5% were resistant to all antibiotics tested. MBL was found in 76.3% and 69.7% of the P. aeruginosa and Acinetobacter spp., respectively. Colistin resistance was observed in three (6.0%) Acinetobacter isolates and eight (8.4%) P. aeruginosa. MIC50 for carbapenems were two to four times higher for MBL-positive compared to MBL-negative isolates, but no difference was seen in MIC for colistin.. Carbapenem resistance was observed to be mediated by MBL in a considerable number of isolates. Colistin is an alternative for infections caused by CA-R isolates; however, MIC testing should be performed whenever clinical use of colistin is considered.

Topics: Acinetobacter; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Carbapenems; Colistin; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections

Polymyxins have recently again become important because of multidrug-resistant (MDR) gram-negative pathogens. The aim of this study was to evaluate the clinical and microbiological efficacy and toxicity of different dosages of colistin in patients infected with MDR microorganisms that were sensitive only to colistin. The study was conducted in the 1,200-bed Ankara Numune Training and Research Hospital. Patients with normal renal function who received colistin for 48 h or more were retrospectively evaluated. Clinical response was defined as resolution of fever and clinical and laboratory findings. Microbiological response was defined as bacteriological eradication from the infection site. Nephrotoxicity was defined as at least two consecutive serum creatinine measurements with an increase of 0.5 mg/dl from baseline at least 24 h apart after 2 or more days of colistin therapy. Twenty-four patients were included in the study: total clinical response was obtained in 17 of 24 (70.8 %) patients and microbiological response in 15 of 24 (62.5 %) patients. Patients were grouped according to colistin dosage of 3 × 1 million units (MU) versus 3 × 2 MU. Clinical response rates were 69.2 % and 72.7 %, respectively (p = 0.65). Microbiological response rate was similar (p = 0.62). Nephrotoxicity was revealed in 1 of 13 patients (7.7 %) for the 3 × 1 MU group and 2 of 11 patients (18.2 %) in the 3 × 2 MU group (p = 0.57). The nephrotoxicity rate was greater with higher dosages of colistin, but the difference was not statistically significant. Renal function of patients receiving higher dosages of colistin should be more closely monitored.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Pneumonia, Bacterial; Treatment Outcome; Urinary Tract Infections; Young Adult

This study investigates the clinical and epidemiological features of Chryseobacterium indologenes infections and antimicrobial susceptibilities of C indologenes.. With 215 C indologenes isolates between January 1, 2004 and September 30, 2011, at a medical center, we analyzed the relationship between the prevalence of C indologenes infections and total prescription of colistin and tigecycline, clinical manifestation, antibiotic susceptibility, and outcomes.. Colistin and tigecycline were introduced into clinical use at this medical center since August 2006. The increasing numbers of patients with C indologenes pneumonia and bacteremia correlated to increased consumption of colistin (p = 0.018) or tigecycline (p = 0.049). Among patients with bacteremia and pneumonia, the in-hospital mortality rate was 63.6% and 35.2% (p = 0.015), respectively. Administration of appropriate antibiotics showed significant benefit in 14-day survival in patients with C indologenes bloodstream infection (p = 0.040). In bacteremic patients, old cardiovascular accident (p = 0.036) and cancer (p = 0.014) were the most common comorbidity. The most common co-infection pathogen in patients with C indologenes pneumonia was Acinetobacter baumannii (36/91, 39.6%), followed by Pseudomonas aeruginosa (23/91, 25.3%), carbapenem-resistant A baumannii (22/91, 24.2%), and Klebseilla pneumoniae (13/91, 14.3%). Antimicrobial susceptibility testing of the 215 isolates showed that trimethoprim-sulfamethoxazole was the most active agent (susceptibility rate: 87.4%), followed by cefoperazone-sulbactam (48.0%).. The present study showed a trend of increasing prevalence of C indologenes infection after introduction of colistin and tigecycline usage. The bacteremia group had higher mortality rate than the pneumonia group. Increasing resistance to piperacillin-tazobactam, ceftazidime, cefepime, and newer fluoroquinolone were noticed in our analysis. Trimethoprim-sulfamethoxazole was a potential antimicrobial agent in vitro for C indologenes. To avoid collateral damage, we emphasize the importance of antibiotic stewardship program.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Chryseobacterium; Colistin; Drug Prescriptions; Drug Resistance, Bacterial; Female; Flavobacteriaceae Infections; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Bacterial; Prevalence; Survival Analysis; Tigecycline

Colistin is increasingly used for the treatment of multidrug-resistant gram-negative infections. However, colistin dosing varies greatly and the optimal regimen is unknown. The purpose of this study was to determine if colistin dosing correlates with patient outcomes.. This retrospective study included patients with gram-negative bacteremia treated with intravenous colistin for at least 72 hours. The primary objective was to determine if colistin dose (mg of colistin base activity/kg/day) independently predicts day-7 microbiological success. Secondary objectives included evaluation for an association between colistin dose and 7-day mortality, 28-day mortality, and the development of acute kidney insufficiency (AKI).. Seventy-six patients were included in the analysis, with 52 patients (68%) achieving 7-day microbiological success. The median colistin dose was significantly higher in patients who achieved microbiological success (2.9 vs 1.5 mg/kg/day; P = .011). After adjusting for baseline severity of illness and concomitant tigecyline use, higher colistin dose independently correlated with microbiological success (adjusted odds ratio per 1 mg/kg/day = 1.74; 95% confidence interval, 1.11-2.71; P = .015). The median colistin dose was also significantly higher among survivors at day 7 (2.7 vs 1.5 mg/kg/day; P = .007). However, no difference was observed in colistin dose when comparing survivors and nonsurvivors at day 28. A significantly higher colistin dose was given to patients who developed AKI during therapy (3.8 vs 1.6 mg/kg/day; P < .001).. Higher colistin dose independently predicted microbiological success, which may partially explain the similar association with 7-day mortality. However, higher colistin doses may also precipitate worsening renal function.

Topics: Anti-Bacterial Agents; Bacteremia; Colistin; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Injections, Intravenous; Male; Middle Aged; Retrospective Studies; Treatment Outcome

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

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

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Bacterial; Drug Synergism; France; Humans; Microbial Sensitivity Tests; Sulbactam

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

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

Extremely drug-resistant (XDR; i.e. resistant to all antibiotics except colistin or tigecycline) Acinetobacter baumannii has emerged as one of the most common and highly antibiotic-resistant causes of infection. Diabetes is a risk factor for acquisition of and worse outcomes from A. baumannii infection. We sought to develop diabetic mouse models of A. baumannii bacteraemia and pneumonia and validate these models by comparing the efficacy of antibiotic treatment in these models with the established neutropenic mouse models.. Diabetic or neutropenic mice were infected via intravenous inoculation or inhalation in an aerosol chamber with an XDR A. baumannii. Treatment with colistin started 24 h after infection and continued daily for 7 days. Survival served as the primary endpoint while tissue bacterial burden and histopathological examination served as secondary endpoints.. Lethal infection was achieved for the neutropenic and diabetic mice when infected intravenously or via inhalation. Neutropenic mice were more susceptible to infection than diabetic mice in the pneumonia model and equally susceptible in the bacteraemia model. Both models of bacteraemia were sensitive enough to detect virulence differences among different clinical strains of A. baumannii. In the pneumonia model, colistin treatment was effective in improving survival, reducing lung bacterial burden and histologically resolving the infection compared with placebo only in diabetic mice.. We developed novel models of A. baumannii bacteraemia and pneumonia in diabetic mice. These models can be used to study mechanisms of infection, develop immunotherapeutic strategies and evaluate drug efficacies against highly lethal A. baumannii infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacteremia; Bacterial Load; Colistin; Diabetes Complications; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Histocytochemistry; Humans; Mice; Mice, Inbred BALB C; Mice, Inbred ICR; Pneumonia, Bacterial; Survival Analysis; Treatment Outcome

In view of reports of colistin-induced neurotoxicity in infected patients, the aim of this study was to assess whether the integrity of the blood-brain barrier (BBB) and the brain uptake of colistin are altered in the presence of systemic Pseudomonas aeruginosa infection. Bacteremia was confirmed 8 h after intramuscular administration of P. aeruginosa ATCC 27853 to Swiss Outbred mice, at which time a single subcutaneous dose of colistin sulfate (40 mg/kg of body weight) or an intravenous dose of [(14)C]sucrose (2 μCi) was administered. Despite a substantial elevation in plasma levels of the proinflammatory cytokines tumor necrosis factor alpha, interleukin-1β, and interleukin-6 during bacterial infection, the brain uptake of colistin was similar between infected and noninfected mice with AUC(brain)/AUC(plasma) (where AUC(brain) is the area under the brain concentration-time curve and AUC(plasma) is the area under the plasma concentration-time curve) ratios of 0.023 and 0.024, respectively. Similarly, the brain-to-plasma ratios of [(14)C]sucrose were no different between infected and noninfected mice, consistent with a lack of effect of bacteremia on BBB integrity. To further correlate any relationship between BBB disruption and plasma levels of proinflammatory cytokines, BBB integrity, colistin brain uptake, and plasma proinflammatory cytokines were measured following the administration of Salmonella enterica lipopolysaccharide (LPS), an agent known to induce BBB disruption. Despite LPS inducing a 4-fold increase in colistin brain uptake and a significant (P < 0.05) 1.2-fold increase in [(14)C]sucrose BBB penetration, plasma cytokine levels were lower with LPS treatment relative to those obtained with bacterial infection with P. aeruginosa. This study demonstrates that the brain uptake of colistin is not increased in mice during P. aeruginosa-induced systemic bacteremia despite a significant increase in plasma levels of three proinflammatory cytokines.

Topics: Animals; Bacteremia; Blood-Brain Barrier; Brain; Colistin; Cytokines; Lipopolysaccharides; Male; Mice; Pseudomonas aeruginosa; Pseudomonas Infections

Infections caused by extensive drug-resistant Acinetobacter baumannii (XDR-AB) have been increasingly observed and are associated with a high mortality rate. We present our experience using aerosolized colistin for the treatment of ventilator-associated pneumonia (VAP) due to XDR-AB in neonates.. The clinical data of neonates who received aerosolized 4 mg per kg of colistin base twice daily as an adjunctive therapy for VAP caused by XDR-AB between July 2008 and September 2009 were retrospectively reviewed. The outcomes were compared with the neonates with VAP from XDR-AB in October 2006-September 2007 who did not receive aerosolized colistin.. During the study period, eight neonates (three preterm and five term neonates) with VAP caused by XDR-AB received aerosolized colistin. All isolated pathogens from the tracheobronchial specimens of the eight patients were XDR-AB susceptible to colistin only. Six patients received aerosolized colistin without concomitant intravenous colistin. All children were cured with eradication of XDR-AB from respiratory secretions. Seven patients survived and were discharged from the hospital, and one died from bacterial sepsis unrelated to the VAP episode. There were no clinical or laboratory adverse events related to aerosolized colistin. Compared to the seven neonates in the earlier period, the neonates who received aerosolized colistin had higher birth weight and gestational age, and lower mortality rate (13% vs. 71%, P=0.04).. Aerosolized colistin may be a useful adjunctive therapy in VAP due to XDR-AB. The use of aerosolized colistin in neonates should be investigated in a larger controlled study.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Administration, Inhalation; Aerosols; Anti-Bacterial Agents; Bacteremia; Birth Weight; Colistin; Drug Resistance, Bacterial; Female; Gestational Age; Humans; Infant, Newborn; Male; Pneumonia, Ventilator-Associated; Retrospective Studies; Thailand; Treatment Outcome

Nosocomial infection due to multidrug-resistant Gram-negative pathogens in intensive care units is a challenge for clinicians and microbiologists, and has led to resurgence of parenteral colistin use in the last decade. Safety and efficacy data regarding intravenous colistin (colistimethate) use in neonates is sparse. We present our experience of efficacy and safety of colistimethate in the treatment of sepsis in critically sick term and preterm neonates.. The records of the neonates who received colistimethate in a neonatal intensive care unit of a tertiary care center from January 2009 to December 2009 were reviewed.. Eighteen critically sick neonates (10 term and 8 preterm) received 21 courses of colistimethate (dose ranging from 50,000 to 75,000 IU/kg/d) for treatment of pneumonia, blood stream infections, meningitis, and empyema thoracis. The isolated pathogens in decreasing order of frequency were Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonos aeruginosa, and Enterobacter. Mean duration of colistimethate was 13.1 days/course (range: 5-21 days). At least one other antibiotic was coadministered in all courses. A favorable clinical outcome occurred in 16 of 21 (76%) courses, 5 patients died due to severe sepsis with multiple organ dysfunction. Microbiologic clearance was documented in 17 courses. Increase in serum creatinine by > 0.5 mg/dL above baseline in 2 babies was associated with the presence of multiple organ dysfunction syndrome in both and coadministration of netilmicin in one.. Colistimethate intravenous administration appears to be safe and efficacious for multidrug-resistant Gram-negative infections in neonates, including preterm and extremely low birth weight neonates.

Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Bacteremia; Colistin; Critical Care; Cross Infection; Drug Resistance, Multiple, Bacterial; Enterobacter; Female; Gram-Negative Bacterial Infections; Humans; Infant, Newborn; Infusions, Intravenous; Klebsiella pneumoniae; Male; Pseudomonas aeruginosa; Treatment Outcome

Despite the identification of Acinetobacter baumannii isolates that demonstrate susceptibility to only colistin, this antimicrobial agent was not available in Korea until 2006. The present study examined the outcomes of patients with multidrug resistant (MDR) Acinetobacter species bloodstream infection and who were treated with or without colistin as part of their regimen. The colistin group was given colistin as part of therapy once colistin became available in 2006. The non-colistin group was derived from the patients who were treated with other antimicrobial regimens before 2006. Mortality within 30 days of the onset of bacteremia occurred for 11 of 31 patients in the colistin group and for 15 of 39 patients in the non-colistin group (35.5% vs 38.5%, respectively, P = 0.80). Renal dysfunction developed in 50.0% of the 20 evaluable patients in the colistin group, but in 28.6% of the 35 evaluable patients in the non-colistin group (P = 0.11). On multivariate analysis, only an Acute Physiological and Chronic Health Evaluation II score ≥ 21 was associated with mortality at 30 days. This result suggests that administering colistin, although it is the sole microbiologically appropriate agent, does not influence the 30 day mortality of patients with a MDR Acinetobacter spp. bloodstream infection.

Topics: Acinetobacter; Acinetobacter Infections; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; APACHE; Bacteremia; Child; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Middle Aged; Republic of Korea; Retrospective Studies; Risk; Treatment Outcome

Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) is an emerging multidrug-resistant nosocomial pathogen. This is a retrospective chart review describing the outcomes and treatment of 60 cases of CR-Kp bloodstream infections. All CR-Kp isolated from blood cultures were identified retrospectively from the microbiology laboratory from January 2007 to May 2009. Clinical information was collected from the electronic medical record. Patients with 14-day hospital mortality were compared to those who survived 14 days. The all-cause in-hospital and 14-day mortality for all 60 CR-Kp bloodstream infections were 58.3% and 41.7%, respectively. In this collection, 98% of tested isolates were susceptible in vitro to tigecycline compared to 86% to colistimethate, 45% to amikacin, and 22% to gentamicin. Nine patients died before cultures were finalized and received no therapy active against CR-Kp. In the remaining 51 patients, those who survived to day 14 (n = 35) were compared to nonsurvivors at day 14 (n=16). These patients were characterized by both chronic disease and acute illness. The 90-day readmission rate for hospital survivors was 72%. Time to active therapy was not significantly different between survivors and nonsurvivors, and hospital mortality was also similar regardless of therapy chosen. Pitt bacteremia score was the only significant factor associated with mortality in Cox regression analysis. In summary, CR-Kp bloodstream infections occur in patients who are chronically and acutely ill. They are associated with high 14-day mortality and poor outcomes regardless of tigecycline or other treatment regimens selected.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Minocycline; Prognosis; Retrospective Studies; Tigecycline; Treatment Outcome

To determine whether the susceptibilities and the trends of nonsusceptibility of imipenem, meropenem, sulbactam, and colistin differed among Acinetobacter baumannii, Acinetobacter genomic species 3 (AGS 3), and Acinetobacter genomic species 13TU (AGS 13TU) over 11 years.. A total of 1,039 nonduplicate blood isolates of A baumannii complex from bacteremic patients between 1997 and 2007 were collected at Taipei Veterans General Hospital and were identified to the species level using a multiplex polymerase chain reaction method and sequence analysis of 16S-23S intergenic spacer. The minimal inhibitory concentrations of antibiotics were determined by the agar dilution method.. The nonsusceptibility rates of carbepenems and sulbactam were highest in A baumannii, which also showed a trend toward increasing rate of carbapenems nonsusceptibility over the 11-year period of the study. AGS 13TU had the highest nonsusceptible rate to colistin, comparably increasing trend of carbapenem nonsusceptiblity as that of A baumannii, and is the only species with increasing sulbactam nonsusceptibility. AGS 3 had the lowest rate of nonsusceptibility to all four antimicrobial agents.. Although A baumannii had the highest nonsusceptibility rate to imipenem, meropenem, and sulbactam over the years, the higher rate of colistin nonsusceptibility and the emergence of nonsusceptibility of carbapenems and sulbactam in AGS 13TU suggested that this species might cause a great problem in the near future.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; beta-Lactams; Cluster Analysis; Colistin; Drug Resistance, Bacterial; Enzyme Inhibitors; Genotype; Hospitals, Veterans; Humans; Microbial Sensitivity Tests; Multiplex Polymerase Chain Reaction; Sequence Analysis, DNA; Sulbactam; Taiwan

Topics: Bacteremia; beta-Lactamases; Calciphylaxis; Coinfection; Colistin; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Middle Aged; Minocycline; Tigecycline

In vitro activities of colistin and other drugs were tested against 221 Klebsiella pneumoniae isolates that were collected between 2006 and 2007 in nine tertiary care South Korean hospitals from patients with bacteremia. The clonality of colistin-resistant K. pneumoniae (CRKP) isolates was assessed by multilocus sequence typing (MLST). We found that 15 isolates (6.8%) were resistant to colistin. MLST showed that CRKP isolates were nonclonal, with colistin resistance in K. pneumoniae occurring independently and not by clonal spreading.

Topics: Anti-Bacterial Agents; Bacteremia; Colistin; Cross Infection; Drug Resistance, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Population Surveillance; Republic of Korea

Both bacteremia and biliary cast syndrome are serious post-transplant complications in liver transplant recipients. In the setting of increasing drug resistance in the current era, management of infections caused by multidrug-resistant (MDR) bacteria has proven challenging. We present a case of a liver transplant recipient who developed biliary cast syndrome and intractable MDR Pseudomonas bacteremia that failed to resolve with conventional antimicrobial therapy and which was finally controlled by a novel combination regimen of colistimethate, doripenem, and tobramycin. Future studies validating the clinical efficacy of this combination strategy are warranted.

Topics: Anti-Bacterial Agents; Bacteremia; Bile Duct Diseases; Carbapenems; Colistin; Doripenem; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Liver Transplantation; Male; Microbial Sensitivity Tests; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Tobramycin; Treatment Outcome

The spread of antimicrobial resistance among members of the Enterobacteriaceae is a significant clinical threat. We report the treatment of pan-resistant Klebsiella pneumoniae bacteraemia with combination tigecycline and colistin in a 49-year-old male and review available therapeutic options. Despite a poor prognosis, the patient recovered, but remains colonized with the pan-resistant isolate.

Topics: Animals; Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia, Bacterial; Tigecycline

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Blood; Chryseobacterium; Colistin; Flavobacteriaceae Infections; Humans; Infant; Infant, Newborn; Minocycline; Taiwan; Tigecycline; Young Adult

Meropenem (MEM; 2 g/8 hr; minimum inhibitory concentration [MIC] = 256 mg/L) plus sulbactam (SUL; 1 g/8 hr; MIC = 128 mg/L) (two-drug-therapy period), and subsequent additional intravenous colistin (COL; 2.5 mg/kg/12 hr) and intraventricular (COL, 5 mg/day; MIC = 1 mg/L) (three-drug-therapy period) were sequentially used in a patient with postneurosurgery bacteremic meningitis due to a multidrug-resistant Acinetobacter baumannii (MDRAB) isolate (AB(1)). We detected 4- to 32-fold increases in peak or trough cerebrospinal fluid bactericidal titer and serum bactericidal titer in three-drug-therapy period when comparing to those in two-drug-therapy period. The time-kill study with MEM, SUL, and COL alone or varied combinations (all at 1 x MIC) against AB(1) and another genetically nonrelated MDRAB isolate (AB(134) [MICs of MEM = 64 mg/L, SUL = 16 mg/L, and COL = 1 mg/L]) was performed. The two-drug combinations (MEM + SUL, MEM + COL, and SUL + COL) each elicited different inhibitory effect on AB(1) and AB(134) at 6 hr. Bacterial regrowth at 24 hr was observed in the experiments in which the MDRAB isolate was inhibited earlier by COL alone (AB(1) and AB(134)), by MEM plus SUL (AB(1)), and by MEM plus COL (AB(134)), but not in SUL plus COL, and MEM + SUL + COL. Combined use of COL with MEM and/or SUL may provide good therapeutic options, even though MEM and SUL are in vitro resistance to the MDRAB.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Male; Meningitis, Bacterial; Meropenem; Microbial Sensitivity Tests; Neurosurgical Procedures; Postoperative Complications; Sulbactam; Thienamycins; Time Factors

Multidrug-resistant Pseudomonas aeruginosa, especially metallo-beta-lactamase (MBL)-producing P. aeruginosa, is an important pathogen in nosocomial infection and emergence of this pathogen has revived interest in polymyxin B (PMB) and colistin (COL). In this study, we evaluated the efficacies of PMB, COL and other antipseudomonal agents against IMP-type MBL-producing P. aeruginosa both in vitro and in vivo. A total of 75 isolates of bla(IMP)-positive P. aeruginosa obtained from clinical specimens (94.6% of isolates demonstrated resistance to beta-lactam, fluoroquinolone and aminoglycoside agents) were evaluated in the in vitro study. More than 90% of the examined isolates were susceptible to PMB (minimum inhibitory concentration for 50/90% of the isolates (MIC(50)/MIC(90)) 4/4 mg/L), although COL was less potent (MIC(50)/MIC(90) 8/16 mg/L). Cyclophosphamide-treated mice were intraperitoneally inoculated with bla(IMP)-positive P. aeruginosa. Treatment with PMB, but not COL, imipenem/cilastatin or aztreonam, significantly improved the survival rate and decreased the number of bacteria in the blood in a dose-dependent manner. Our results indicate that, among the agents studied, PMB is the most effective agent against bla(IMP)-positive P. aeruginosa.

Topics: Animals; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Colistin; Colony Count, Microbial; Drug Resistance, Bacterial; Male; Mice; Microbial Sensitivity Tests; Polymyxin B; Pseudomonas aeruginosa; Pseudomonas Infections; Reverse Transcriptase Polymerase Chain Reaction; Survival Analysis

We report the use of tigecycline, firstly with colistin and finally alone, in a patient with a persistent breakthrough bacteremia due to a Klebsiella pneumoniae isolate harboring a metallo-beta-lactamase (VIM-1) and an extended-spectrum beta-lactamase (SHV-12). Time-kill studies demonstrated that the combination of both compounds was synergistic along the first 12 h, suppressing the regrowth observed after 3 to 6 h when colistin was tested alone.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Colistin; Drug Synergism; Drug Therapy, Combination; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Microbial Viability; Minocycline; Tigecycline

Infections due to multidrug-resistant (MDR) Gram-negative pathogens in the ICU have prompted the use of colistin, an antibiotic forgotten for decades. The aim of this retrospective observational study was to record and present the emergence of colistin-resistant Klebsiella pneumoniae (CRKB) in a Greek ICU.. In a new university tertiary hospital, the first patients admitted in the ICU were already colonized or infected with MDR pathogens, and this led to frequent colistin use as part of empirical or microbiologically documented therapy. Colistin resistance was defined as MIC >4 mg/L by the Etest method. All CRKB isolated in surveillance cultures or clinical specimens in the ICU during the period 2004-5 were recorded along with patients' characteristics.. Eighteen CRKB were isolated from 13 patients over a 16 month period, representing either colonizing or infective isolates. Patients' mean age was 70 years, with a mean APACHE II score at admission of 22. They all had a long hospitalization (median 69 days) and a long administration of colistin (median 27 days). Colistin-resistant isolates were implicated as pathogens in two bacteraemias, a ventilator-associated pneumonia and two soft tissue infections. Repetitive extragenic palindromic PCR identified six distinct clones, and horizontal transmission was also documented.. Selective pressure due to extensive or inadequate colistin use may lead to the emergence of colistin resistance among K. pneumoniae isolates, jeopardizing treatment options in the ICU, potentially increasing morbidity and mortality of critically ill patients and necessitating prudent use of colistin.

Topics: Aged; Anti-Bacterial Agents; APACHE; Bacteremia; Colistin; Drug Resistance, Bacterial; Drug Utilization; Female; Genes, Bacterial; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Male; Multigene Family; Reverse Transcriptase Polymerase Chain Reaction

In this study, we explored risk factors associated with bacteraemia caused by colistin-susceptible/carbapenem-resistant (Co(S)/Ca(R)) Acinetobacter baumannii. A retrospective cohort study of hospitalised patients with A. baumannii bacteraemia was performed at a tertiary care hospital over a 44-month period. Thirty-nine patients with bacteraemia due to A. baumannii (35 Intensive Care Unit and 4 ward patients) were included in the analysis. Twenty-five patients (64%) had bacteraemia due to Co(S)/Ca(R)A. baumannii and 14 patients (36%) had bacteraemia due to colistin-susceptible/carbapenem-susceptible A. baumannii. Mortality was 56% (14/25) and 35.7% (5/14) for patients in the two groups, respectively (P=0.22). Bivariate analysis showed that prior exposure to fluoroquinolones (P=0.01) and antipseudomonal penicillins (P=0.004) as well as a higher number of antibiotics in use on the day of bacteraemia (P=0.02) were associated with isolation of a Co(S)/Ca(R) strain among patients with A. baumannii bacteraemia. Multivariate analysis using a backward logistic regression model showed that only exposure to fluoroquinolones was associated with development of Co(S)/Ca(R)A. baumannii bacteraemia (odds ratio=11.6; 95% confidence interval 2.4-55.9; P=0.02). The appearance of Co(S)/Ca(R)A. baumannii infections represents a major threat to critically ill hospitalised patients. Exposure to fluoroquinolones is an independent risk factor for development of Co(S)/Ca(R)A. baumannii bacteraemia.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; Blood; Carbapenems; Cohort Studies; Colistin; Female; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Penicillins; Quinolones; Retrospective Studies; Risk Factors

Topics: Acinetobacter baumannii; Acinetobacter calcoaceticus; Aged; Anti-Bacterial Agents; Bacteremia; Calcaneus; Colistin; Humans; Male; Microbial Sensitivity Tests; Osteomyelitis

Topics: Anti-Bacterial Agents; Bacteremia; Ciprofloxacin; Colistin; Drug Resistance, Bacterial; Gram-Negative Anaerobic Bacteria; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; Neoplasms

Nosocomial infections due to MDR P. aeruginosa are an increasing problem. Therapeutical options are few. We describe two haematological patients with severe neutropenia and systemic infection due to MDR P. aeruginosa treated successfully with colistin plus ceftazidime. Severe adverse events were not described.

Topics: Acute Disease; Adrenal Cortex Hormones; Aged; Anemia, Refractory, with Excess of Blasts; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Bacteremia; Ceftazidime; Colistin; Colitis; Disease Susceptibility; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Fatal Outcome; Female; Humans; Infusions, Intravenous; Leukemia, Myeloid; Lymphoma, Non-Hodgkin; Male; Middle Aged; Neoplasms, Second Primary; Peritonitis; Postoperative Complications; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pseudomonas Infections; Radiation Injuries; Spinal Neoplasms; Typhlitis

The intravenous use of polymyxins has been considered to be associated with considerable nephrotoxicity and neurotoxicity. For this reason, the systemic administration of polymyxins had been abandoned for about 20 years in most areas of the world. However, the problem of infections due to multidrug-resistant (MDR) Gram-negative bacteria such us Pseudomonas aeruginosa and Acinetobacter baumanniii has led to the re-use of polymyxins. Our objective was to study the toxicity of prolonged intravenous administration of colistin (polymyxin E).. An observational study of a retrospective cohort at "Henry Dunant" Hospital, a 450-bed tertiary care center in Athens, Greece, was undertaken.Patients who received intravenous colistin for more than 4 weeks for the treatment of multidrug resistant Gram-negative infections were included in the study. Serum creatinine, blood urea, liver function tests, symptoms and signs of neurotoxicity were the main outcomes studied.. We analyzed data for 19 courses of prolonged intravenous colistin [mean duration of administration (+/- SD) 43.4 (+/- 14.6) days, mean daily dosage (+/- SD) 4.4 (+/- 2.1) million IU, mean cumulative dosage (+/- SD) 190.4 (+/- 91.0) million IU] in 17 patients. The median creatinine value increased by 0.25 mg/dl during the treatment compared to the baseline (p < 0.001) but returned close to the baseline at the end of treatment (higher by 0.1 mg/dl, p = 0.67). No apnea or other evidence of neuromuscular blockade was noted in any of these patients who received prolonged treatment with colistin.. No serious toxicity was observed in this group of patients who received prolonged intravenous colistin. Colistin should be considered as a therapeutic option in patients with infections due to multidrug resistant Gram-negative bacteria.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacteremia; Bacterial Infections; Biliary Tract; Cohort Studies; Colistin; Creatinine; Female; Humans; Infusion Pumps; Kidney; Liver; Liver Function Tests; Male; Middle Aged; Nervous System; Neuromuscular Junction; Pneumonia; Retrospective Studies; Time Factors; Urea

Continuous intravenous colistin (2,000,000 units per 24 h) was administered in a 41-y-old patient with Acinetobacter baumannii bacteraemia, which led to the cure of the infection. The isolated microorganism was a multi-resistant strain (it was sensitive only to colistin). In addition, the patient had developed allergic reactions to previously administered antimicrobial agents of several classes during his hospitalization. Continuous intravenous infusion of colistin proved to be a salvage regimen, which led to cure of a bacteraemia due to a multi-resistant isolate, without showing any allergic cross-reactivity with other antibiotics.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Bacteremia; Colistin; Diagnosis, Differential; Drug Resistance, Bacterial; Humans; Infusions, Intravenous; Male

We suggest a novel approach to enhancing antimicrobial drug action by utilizing engineered peptide conjugates. Our most potent conjugates, [fMLF]PMBN and [fMLF]PMEN, are nonapeptides derived from polymyxin B's (PMB's) cyclic moiety (Thr-Dab-cyclo[Dab-Dab-d-Phe-Leu-Dab-Dab-Thr], where Dab is 2,4-diaminobutyric acid) and polymyxin E's (PME's) cyclic moiety (Thr-Dab-cyclo[Dab-Dab-d-Leu-Leu-Dab-Dab-Thr]), respectively, attached to a linear tail comprised of formyl-Met-Leu-Phe (fMLF). The cyclic part binds to gram-negative lipopolysaccharides, rendering the bacterial outer membrane permeable to hydrophobic antibiotics. The tail confers chemotactic and opsonic activities upon the conjugates. These two activities appear to be the basis for the conjugates' antibacterial activities. The conjugates are 8 to 10 times less toxic than the parent PMB or PME antibiotics. Fourteen of 18 mice lethally challenged with erythromycin-resistant Klebsiella pneumoniae survived following intraperitoneal administration of erythromycin and [fMLF]PMBN, whereas erythromycin or the peptide conjugate alone had no effect. Moreover, the clearance of Klebsiella from blood was markedly enhanced by intravenous injection of the [fMLF]PMEN peptide conjugate compared to the clearance of the organism from the mice treated with buffer alone as a control and was similar to that achieved by the PME antibiotic. Blood clearance was also significantly enhanced by administration of PMEN either alone or in a mixture with fMLF, although the effect was less than that produced by the peptide conjugate. Since resistance to polymyxins, the parent molecules of the synthetic cyclic peptides, is rare, the emergence of bacteria resistant to the antimicrobial properties of the peptide conjugates may be precluded as well.

Topics: Animals; Anti-Bacterial Agents; Bacteremia; Blood; Cell Membrane Permeability; Chemotaxis; Colistin; Drug Resistance, Bacterial; Erythromycin; Gram-Negative Bacteria; Humans; Klebsiella Infections; Klebsiella pneumoniae; Macrophages, Peritoneal; Mice; Microbial Sensitivity Tests; Opsonin Proteins; Peptides; Polymyxin B

MSI-78 is a 22 amino acid amphipathic peptide with potent antimicrobial activity against Gram-positive and Gram-negative organisms, including antibiotic-resistant strains. In this study, we assessed the in vitro activity of MSI-78 alone and in combination with eight clinically used antimicrobial agents against several strains of Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli isolated from blood of neutropenic febrile patients. Antimicrobial activity of MSI-78 was measured by minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), time-kill studies and checkerboard titration method. The Gram-negative isolates were susceptible to the peptide at concentrations in the range 0.50-16 mg/L, while staphylococci showed lower susceptibility. MSI-78 demonstrated a higher antimicrobial activity than colistin against Gram-negative organisms. The checkerboard titration method demonstrated synergy when the peptide was combined with beta-lactams. These results provide evidence for the potential use of MSI-78 in the management of severe infections in neutropenic patients.

Topics: Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Bacteremia; Bacteria; beta-Lactams; Colistin; Colony Count, Microbial; Drug Therapy, Combination; Escherichia coli; Humans; Microbial Sensitivity Tests; Neutropenia; Pseudomonas aeruginosa; Staphylococcus aureus; Staphylococcus epidermidis

The in-vivo activity of colistin was evaluated in an experimental rabbit model of Acinetobacter baumannii endocarditis with a strain susceptible to colistin and intermediate to imipenem. Compared to a control group, colistin was effective (p < 0.05) in bacterial clearance from blood and in the sterilisation of blood cultures, but was not effective in clearing A. baumannii from vegetations. Thus, although colistin may be effective in treating bacteraemia caused by susceptible strains of A. baumannii, it may not be a suitable treatment for endocarditis, perhaps because of poor penetration into vegetations and a low C(max)/MIC ratio in tissue.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacteremia; Colistin; Colony Count, Microbial; Disease Models, Animal; Endocarditis, Bacterial; Heart Valves; Humans; Microbial Sensitivity Tests; Rabbits; Treatment Outcome

The emergence of infections caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter spp. has necessitated the search for alternative parenteral agents such as the polymyxins. The National Committee for Clinical Laboratory Standards (NCCLS) documents do not currently provide interpretative criteria for the testing of the polymyxins, colistin and polymyxin B. Therefore, an evaluation of the antimicrobial activity of colistin and polymyxin B was initiated using 200 bloodstream infection pathogens collected through the SENTRY Antimicrobial Surveillance Program. All susceptibility tests were performed according to the NCCLS recommendations. Polymyxin B and colistin displayed a nearly identical spectrum of activity, exhibiting excellent potency against P. aeruginosa (MIC(90), 2 microg/ml) and Acinetobacter sp. (MIC(90), 2 microg/ml). In contrast, they showed limited activity against some other nonfermentative bacilli such as Burkholderia cepacia (MIC(90), >/=128 microg/ml). Excellent correlation was achieved between broth microdilution and agar dilution tests (r = 0.96 to 0.98); 94.3% of the results were +/-1 log(2) dilution between the methods used for both compounds. At a resistance breakpoint of >/=4 microg/ml for both agents, unacceptable false-susceptible or very major errors were noted for colistin (5%) and polymyxin B (6%). Modified zone criteria for colistin (/=14 mm) and polymyxin B (/=14 mm) were suggested, but some degree of error persisted (>/=3.5%). It is recommended that all susceptible disk diffusion results be confirmed by MIC tests using the preferred reference NCCLS method. The quality control (QC) ranges listed in the product package insert require an adjusted range by approximately 3 mm for both NCCLS gram-negative quality control strains. This evaluation of in vitro susceptibility test methods for the polymyxin class drugs confirmed continued serious testing error with the disk diffusion method, the possible need for breakpoint adjustments, and the recalculation of disk diffusion QC ranges. Clinical laboratories should exclusively use MIC methods to assist the therapeutic application of colistin or polymyxin B until disk diffusion test modifications are sanctioned and published by the NCCLS.

Topics: Anti-Bacterial Agents; Bacteremia; Colistin; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; Microbiology; Polymyxin B; Quality Control

To evaluate the effect of total bowel decontamination (TD) and selective bowel decontamination (SD) in a non-protective environment clinical and laboratory data of children treated for acute leukaemia between 1983 and 1991 were analysed retrospectively. From 1983 until 1989 34 patients [18 acute non-lymphoblastic leukaemia (ANLL) patients, 16 acute lymphoblastic leukaemia (ALL) patients] received TD and 31 patients (8 ANLL patients, 23 ALL patients) received SD from 1987 until 1991. TD consisted of colistin sulphate, neomycin, cephaloridine and amphotericin B orally as well as Orabase and sterilized food, while the patients were nursed in a single room. SD consisted of oral colistin sulphate, neomycin and amphotericin B. Those patients with ANLL were nursed in a single room; patients with ALL were nursed in a single room during remission induction therapy only. All patients except those with ANLL receiving TD received Pneumocystis carinii pneumonia prophylaxis with cotrimoxazole. Because the two groups were heterogeneous for diagnosis and chemotherapy the occurrence of fever (central body temperature at least 38.5 degrees C) and major infections (septicaemia of infections of the deep tissues or organs) were registered during periods of neutropenia (neutrophilic granulocytes < or = 500/mm3 for at least 8 days). Patients on TD had 55 periods of neutropenia, patients on SD 80. Patients on TD had 89.1 periods of fever/100 periods of neutropenia whereas patients on SD had 56.3. Also patients on TD had 27.3 major infections/100 periods of neutropenia whereas patients on SD had 11.3. Major infections predominantly consisted of septicaemia caused by gram-positive bacteria. We conclude that, in this study, TD in a non-protective environment does not offer better protection against major infections that SD in patients with ALL or ANLL.

Topics: Adolescent; Amphotericin B; Anti-Bacterial Agents; Bacteremia; Bacterial Infections; Carboxymethylcellulose Sodium; Cephaloridine; Cephalosporins; Child; Child, Preschool; Colistin; Drug Therapy, Combination; Food Handling; Gram-Negative Bacterial Infections; Humans; Infant; Intestines; Leukemia, Myeloid, Acute; Neomycin; Neutropenia; Pneumonia, Pneumocystis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies; Sterilization; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Abortion, Septic; Bacteremia; Chloramphenicol; Cholangitis; Colistin; Escherichia coli Infections; Gastroenteritis; Hydrocortisone; Kanamycin; Polymyxins; Prognosis; Sepsis; Shock, Septic; Streptomycin; Urinary Tract Infections

Topics: Aging; Angiotensins; Bacteremia; Bacteroides; Chloramphenicol; Colistin; Drug Therapy; Enterobacter aerogenes; Escherichia coli Infections; Humans; Iatrogenic Disease; Kanamycin; Metaraminol; Polymyxins; Postoperative Complications; Proteus; Pseudomonas Infections; Sepsis; Sex; Streptomycin; Sympatholytics; Tetracycline; Urinary Tract Infections