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1.
J Clin Microbiol ; 57(2)2019 02.
Article in English | MEDLINE | ID: mdl-30282791

ABSTRACT

Limited methods for colistin MIC determination are available to clinical microbiology laboratories. The purpose of this study was to evaluate the accuracy of the colistin broth disk elution (CBDE) test compared to that of broth microdilution (BMD) for identifying colistin MICs. CBDE was compared to colistin BMD using a collection of Gram-negative bacilli tested at two U.S. microbiology laboratories. The isolates tested included 121 retrospective clinical isolates, 45 prospective clinical isolates, and 6 mcr-1-positive Escherichia coli isolates. CBDE was performed with four 10-ml cation-adjusted Mueller-Hinton broth tubes per isolate, to which 0, 1, 2, and 4 colistin 10-µg disks were added, generating final concentrations in the tubes of 0 (growth control), 1, 2, and 4 µg/ml, respectively. MICs were evaluated visually and interpreted using Clinical and Laboratory Standards Institute breakpoints. Site 2 also compared CBDE to the reference broth macrodilution (BMAD) method (n = 110 isolates). Overall, CBDE yielded a categorical agreement (CA) and essential agreement (EA) of 98% and 99%, respectively, compared to the results of colistin BMD. Very major errors occurred for mcr-1-producing strains, with MICs fluctuating from 2 to 4 µg/ml on repeat testing. The results for all other isolates were in CA with those of BMD. CBDE versus BMAD had an EA of 100% and a CA of 100%. Compared to currently used techniques, CBDE is an easy and practical method to perform colistin MIC testing. Some mcr-1-producing isolates yielded MICs of 2 µg/ml by CBDE and 4 µg/ml by BMD. As such, the results for isolates with colistin MICs of 2 µg/ml by CBDE should be confirmed by the reference BMD method, and isolates with MICs of ≥2 µg/ml should be evaluated for the presence of mcr genes.


Subject(s)
Anti-Bacterial Agents/pharmacology , Colistin/pharmacology , Gram-Negative Bacteria/drug effects , Microbial Sensitivity Tests/methods , Diagnostic Errors/statistics & numerical data , Gram-Negative Bacteria/isolation & purification , Gram-Negative Bacterial Infections/diagnosis , Gram-Negative Bacterial Infections/microbiology , Humans , Prospective Studies , Retrospective Studies , United States
2.
Clin Infect Dis ; 64(3): 257-264, 2017 Feb 01.
Article in English | MEDLINE | ID: mdl-28013264

ABSTRACT

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) are associated with considerable mortality. As mechanisms of carbapenem resistance are heterogeneous, it is unclear if mortality differs based on resistance mechanisms. We sought to determine whether CRE resistance mechanism determination is prognostically informative. METHODS: We conducted an observational study comparing 14-day mortality between patients with carbapenemase-producing (CP)-CRE compared with non-CP-CRE bacteremia. Clinical data were collected on all patients. A comprehensive DNA microarray-based assay was performed on all isolates to identify ß-lactamase-encoding genes. RESULTS: There were 83 unique episodes of monomicrobial CRE bacteremia during the study period: 37 (45%) CP-CRE and 46 (55%) non-CP-CRE. The majority of CP-CRE isolates were bla KPC (92%), followed by bla NDM (5%) and bla OXA-48-type (3%). CP-CRE isolates were more likely to have meropenem minimum inhibitory concentrations (MICs) ≥16 µg/mL, while non-CP-CRE isolates were more likely to have meropenem MICs ≤1 µg/mL (P value < .001). A total of 18 (22%) patients died within 14 days, including 12 (32%) in the CP-CRE group and 6 (13%) in the non-CP-CRE group. Adjusting for severity of illness on day 1 of bacteremia, underlying medical conditions, and differences in antibiotic treatment administered, the odds of dying within 14 days were more than 4 times greater for CP-CRE compared with non-CP-CRE bacteremic patients (adjusted odds ratio, 4.92; 95% confidence interval, 1.01-24.81). CONCLUSION: Our findings suggest that CP-CRE may be more virulent than non-CP-CRE and are associated with poorer outcomes. This underscores the added importance of delineating underlying resistance mechanisms of CRE to direct antibiotic treatment decisions.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacteremia/drug therapy , Bacteremia/mortality , Bacterial Proteins/metabolism , Carbapenems/therapeutic use , Enterobacteriaceae Infections/drug therapy , Enterobacteriaceae Infections/mortality , Enterobacteriaceae/enzymology , beta-Lactam Resistance , beta-Lactamases/metabolism , Adult , Aged , Anti-Bacterial Agents/pharmacology , Bacteremia/blood , Bacterial Proteins/genetics , Carbapenems/pharmacology , Cohort Studies , DNA, Bacterial/genetics , DNA, Bacterial/isolation & purification , Enterobacteriaceae/drug effects , Enterobacteriaceae/pathogenicity , Enterobacteriaceae Infections/blood , Female , Humans , Male , Meropenem , Middle Aged , Retrospective Studies , Thienamycins/pharmacology , Thienamycins/therapeutic use , Treatment Outcome , beta-Lactamases/genetics
3.
J Clin Microbiol ; 52(11): 4039-42, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25143571

ABSTRACT

Five chromogenic agars, evaluated using 400 stool specimens, were found to be superior in sensitivity (range, 89.9 to 93.9%) to bile esculin azide agar with vancomycin (BEAV) agar (84.8%) for detecting vancomycin-resistant enterococci (VRE), and the results were available 24 to 48 h sooner. The time to detection, need for supplemental testing, color distinction, and breakthrough of non-VRE organisms vary among the chromogenic media tested and may factor into the decision to use a particular medium.


Subject(s)
Chromogenic Compounds/metabolism , Culture Media/chemistry , Feces/microbiology , Gram-Positive Bacterial Infections/diagnosis , Gram-Positive Bacterial Infections/microbiology , Vancomycin-Resistant Enterococci/growth & development , Vancomycin-Resistant Enterococci/isolation & purification , Humans , Sensitivity and Specificity , Time Factors , Vancomycin-Resistant Enterococci/metabolism
4.
Clin Infect Dis ; 57(6): 781-8, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23759352

ABSTRACT

BACKGROUND: AmpC ß-lactamase-producing organisms are associated with significant morbidity and mortality. Induction of resistance to third-generation cephalosporins after exposure to these agents complicates treatment options and carbapenems are considered optimal therapy. The role of cefepime, however, remains unclear. Our objective was to compare clinical outcomes for patients receiving cefepime compared with meropenem for invasive infections caused by organisms expressing AmpC ß-lactamases. METHODS: Hospitalized patients with blood, bronchoalveolar lavage, or intra-abdominal fluid cultures growing Enterobacter spp, Serratia spp, or Citrobacter spp were evaluated using the cefotetan-boronic acid disk test and the cefotetan-cloxacillin Etest to identify organisms with AmpC ß-lactamase production from February 2010 to January 2011. In patients with organisms hyperproducing AmpC ß-lactamases (positive by both methods), clinical outcomes for patients receiving cefepime or meropenem therapy were compared. To minimize the possibility of treatment selection bias, 1:1 nearest neighbor propensity score matching was performed prior to regression analysis. RESULTS: Of 399 patients meeting eligibility criteria, 96 (24%) had confirmed infections with AmpC ß-lactamase-producing organisms. Propensity score matching of patients infected with AmpC ß-lactamase-positive organisms treated with cefepime or meropenem yielded 32 well-balanced patient pairs with no difference in 30-day mortality (odds ratio, 0.63; 95% confidence interval [CI], .23-2.11; P = .36) or length of hospital stay after infection (relative risk, 0.96; 95% CI, .79-1.26; P = .56) between the 2 groups. CONCLUSIONS: Cefepime may be a reasonable option for the treatment of invasive infections due to AmpC ß-lactamase-producing organisms, particularly when adequate source control is achieved.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacterial Proteins/biosynthesis , Cephalosporins/therapeutic use , Enterobacteriaceae Infections/drug therapy , Enterobacteriaceae/enzymology , beta-Lactamases/biosynthesis , Adult , Cefepime , Cohort Studies , Enterobacteriaceae/drug effects , Enterobacteriaceae/isolation & purification , Enterobacteriaceae Infections/microbiology , Hospitalization , Humans , Meropenem , Microbial Sensitivity Tests , Middle Aged , Propensity Score , Thienamycins/therapeutic use , beta-Lactam Resistance
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