Michael Malczynski

Increasing Incidence of Linezolid-Intermediate or -Resistant, Vancomycin-Resistant Enterococcus faecium Strains Parallels Increasing Linezolid Consumption

ABSTRACT Clinical enterococcal resistance to linezolid is defined by the presence of the G2576T mutation. We evaluated the incidence of genetically proven linezolid resistance among vancomycin-resistant Enterococcus faecium strains and linezolid consumption for a possible association. A relationship was found (r2 = 0.73, P = 0.03) and predicts increasing resistance with current trends of linezolid use.

Impact of Carbapenem Resistance and Receipt of Active Antimicrobial Therapy on Clinical Outcomes of Acinetobacter baumannii Bloodstream Infections

ABSTRACT Nosocomial Acinetobacter baumannii bloodstream infections occur with significant prevalence and mortality. The relationship between carbapenem resistance in A. baumannii and patient outcomes remains unclear. A retrospective cohort study was conducted on patients with A. baumannii bacteremia. Outcomes, controlling for confounders, were compared for carbapenem-nonresistant A. baumannii (CNRAB) and carbapenem-resistant A. baumannii (CRAB). The primary outcome studied was all-cause hospital mortality, and the secondary endpoints evaluated were time to mortality, time to negative cultures, and length of stay postinfection for survivors. A total of 79 patients, 37 infected with CRAB and 42 with CNRAB, were studied. Hospital mortality was greater in the CRAB group as determined based on bivariate analysis (P < 0.01); however, this effect was nullified when controlling for relevant confounders with logistic regression and a Cox proportional-hazards model (P = 0.71 and 0.75, respectively). Values for time to mortality and time to negative cultures did not differ between the groups. The median number of days of stay postinfection for survivors was greater for the CRAB group than the CNRAB group (14 versus 6.5; P < 0.01). Patients who received active antimicrobial therapy were less likely to die (93.5% versus 74.2%; P = 0.02), regardless of carbapenem susceptibility classifications, and this result was robust in the multivariate model (P = 0.02). Trends existed for improved outcomes in patients receiving an active beta-lactam, and patients fared worse if they had received a polymyxin as an active agent. Patients with CRAB bloodstream infections were more chronically ill and had more comorbidities. Inactive therapy was more important than carbapenem susceptibility with respect to outcomes, was a strong predictor of death, and is potentially modifiable.

Characterization of Genetic Diversity of Carbapenem-Resistant Acinetobacter baumannii Clinical Strains Collected from 2004 to 2007

ABSTRACT Genotypes of carbapenem-resistant Acinetobacter baumannii collected by the clinical microbiology laboratory of a university hospital in Chicago, IL, between 2004 and 2007 were analyzed by pulsed-field gel electrophoresis. A single genotype established predominance after being introduced in 2005. Analysis of carbapenemases by PCR revealed that imipenem resistance but not meropenem resistance was associated with the presence of blaOXA-23 and blaOXA-40 genes.

Correlations of Antibiotic Use and Carbapenem Resistance in Enterobacteriaceae

ABSTRACT Epidemiological studies have shown a link between carbapenem use and resistance; however, the clinical relationship between antibiotic consumption and the epidemiology of carbapenem-intermediate or -resistant Enterobacteriaceae (CIRE) remains unclear. This study sought to analyze temporal antibiotic consumption trends for relationships with incident CIRE. In total, 310,892 days of therapy and 55 deduplicated CIRE were analyzed. When conservative corrections were applied for multiple comparisons, carbapenem class use and piperacillin-tazobactam use retained significant positive and negative relationships with the incidence of CIRE, respectively.

Multidrug-resistant Pseudomonas aeruginosa cholangitis after endoscopic retrograde cholangiopancreatography: failure of routine endoscope cultures to prevent an outbreak.

BACKGROUND Nosocomial infections due to medical devices are of increasing concern to infection control practitioners. Attempts to prevent such infections have included surveillance cultures of endoscopes and bronchoscopes. In July 2002, the infectious disease consultation service was asked to see three patients with sepsis due to multidrug-resistant Pseudomonas aeruginosa after endoscopic retrograde cholangiopancreatography (ERCP). OBJECTIVE To describe an outbreak of multidrug-resistant P. aeruginosa sepsis after ERCP at an institution that performs routine surveillance cultures of endoscopes. DESIGN A traditional outbreak investigation supplemented by pulsed-field gel electrophoresis (PFGE) was undertaken, including a case-control analysis based on the hypothesis that all infected individuals had their ERCP performed with the same endoscope. SETTING A tertiary-care academic medical center. RESULTS The case-control analysis confirmed the hypothesis that undergoing ERCP with the implicated endoscope was associated with a culture positive for Pseudomonas (P = .01). The available strains were identical by PFGE. This outbreak occurred despite a negative surveillance culture of the implicated endoscope 1 month earlier. CONCLUSIONS Infectious morbidity can occur after endoscopy despite negative surveillance cultures. The practice of routine endoscope cultures does not prevent device-related infectious morbidity.

Quantifying the clinical virulence of Klebsiella pneumoniae producing carbapenemase Klebsiella pneumoniae with a Galleria mellonella model and a pilot study to translate to patient outcomes

BackgroundPrevious studies may have overestimated morbidity and mortality due to Klebsiella pneumoniae producing carbapenemase (KPC) Klebsiella pneumoniae infections because of difficulties in modeling patient comorbidities. This pilot study sought to evaluate KPC virulence by combining clinical and Galleria mellonella models in patients with K. pneumoniae blood stream infections (BSIs).MethodsG. mellonella were inoculated using KPC(+) and KPC(−) isolates from these patients. Extent and rapidity of insect mortality was analyzed. Patients were stratified by KPC BSI status. Clinical outcomes of mortality and length of stay post-infection for survivors (LOS) were analyzed. Median virulence scores calculated from the insect studies were imputed in the clinical model.ResultsThe in-vivo model revealed greater mortality in KPC(−) isolates (p < 0.001). Fifteen patients with KPC(+) BSI were matched with 60 patients with KPC(−) BSI. Hospital mortality was greater in the KPC(+) group versus the KPC(−) group (OR 3.79, 95% CI 1.00 - 14.34). LOS was longer in the KPC(+) group (p < 0.01). Conversely the virulence score attenuated the association between KPC(+) status and mortality and LOS in the final translational models.ConclusionsKPC(+) status was associated with decreased virulence in GM. Opposite findings were observed in patients. This pilot study demonstrates that measured virulence from GM may differ from human estimates of virulence.

Comparison of Testing Methods for Detection of Decreased Linezolid Susceptibility Due to G2576T Mutation of the 23S rRNA Gene in Enterococcus faecium and Enterococcus faecalis

ABSTRACT E-test, Vitek 2, MicroScan, agar dilution, and disk diffusion were compared for detection of decreased linezolid susceptibility due to 23S rRNA gene G2576T mutation among 32 clinical Enterococcus strains initially reported as intermediate or resistant by E-test alone or Vitek 2 confirmed by E-test. Agar and broth dilution methods were in concordance with PCR detection of the mutation, and disk diffusion was somewhat less sensitive but equally specific.

Predictability of Doripenem Susceptibility in Acinetobacter baumannii Isolates Based on Other Carbapenem Susceptibilities and blaOXA Gene Status

Study Objective. To better define the utility of surrogate markers for doripenem susceptibility relative to gold standard microbiology tests.

Unacceptably High Error Rates in Vitek 2 Testing of Cefepime Susceptibility in Extended-Spectrum-β-Lactamase-Producing Escherichia coli

ABSTRACT While a lack of concordance is known between gold standard MIC determinations and Vitek 2, the magnitude of the discrepancy and its impact on treatment decisions for extended-spectrum-β-lactamase (ESBL)-producing Escherichia coli are not. Clinical isolates of ESBL-producing E. coli were collected from blood, tissue, and body fluid samples from January 2003 to July 2009. Resistance genotypes were identified by PCR. Primary analyses evaluated the discordance between Vitek 2 and gold standard methods using cefepime susceptibility breakpoint cutoff values of 8, 4, and 2 μg/ml. The discrepancies in MICs between the methods were classified per convention as very major, major, and minor errors. Sensitivity, specificity, and positive and negative predictive values for susceptibility classifications were calculated. A total of 304 isolates were identified; 59% (179) of the isolates carried blaCTX-M, 47% (143) carried blaTEM, and 4% (12) carried blaSHV. At a breakpoint MIC of 8 μg/ml, Vitek 2 produced a categorical agreement of 66.8% and exhibited very major, major, and minor error rates of 23% (20/87 isolates), 5.1% (8/157 isolates), and 24% (73/304), respectively. The sensitivity, specificity, and positive and negative predictive values for a susceptibility breakpoint of 8 μg/ml were 94.9%, 61.2%, 72.3%, and 91.8%, respectively. The sensitivity, specificity, and positive and negative predictive values for a susceptibility breakpoint of 2 μg/ml were 83.8%, 65.3%, 41%, and 93.3%, respectively. Vitek 2 results in unacceptably high error rates for cefepime compared to those of agar dilution for ESBL-producing E. coli. Clinicians should be wary of making treatment decisions on the basis of Vitek 2 susceptibility results for ESBL-producing E. coli.

Differences in Clinical Outcomes in Patients with Vancomycin-Resistant Enterococci According to Linezolid Susceptibility

Study Objective. To evaluate the differences in clinical outcomes in patients with linezolid‐intermediate or ‐resistant vancomycin‐resistant enterococci (LIRVRE) isolates, as defined by the presence of the G2576T mutation, compared with patients who had linezolid‐susceptible VRE (LSVRE) isolates in order to further discern the clinical relevance of linezolid resistance associated with this mutation.