Use of Novel Antibiograms to Determine the Need for Earlier Susceptibility Testing and Administration for New ß-Lactam/ß-Lactamase Inhibitors in the United States.

Antimicrobial resistance is a global public health threat, and gram-negative bacteria, such as Enterobacterales and Pseudomonas aeruginosa, are particularly problematic with difficult-to-treat resistance phenotypes. To reduce morbidity and mortality, a reduction in the time to effective antimicrobial therapy (TTET) is needed, especially among critically ill patients. The antibiogram is an effective clinical tool that can provide accurate antimicrobial susceptibility information and facilitate early antimicrobial optimization, decrease TTET, and improve outcomes such as mortality, hospital length of stay, and costs. Guidance is lacking on how to validate the susceptibility to new antibacterial agents. Commonly used traditional and combination antibiograms may not adequately assist clinicians in making treatment decisions. Challenges with the current susceptibility testing of new ß-lactam/ß-lactamase inhibitor combinations persist, impacting the appropriate antibacterial choice and patient outcomes. Novel antibiograms such as syndromic antibiograms that incorporate resistant gram-negative phenotypes and/or minimum inhibitory concentration distributions may assist in determining the need for earlier susceptibility testing or help define an earlier optimal use of the new ß-lactam/ß-lactamase inhibitors. The purpose of this review is to emphasize novel antibiogram approaches that are capable of improving the time to susceptibility testing and administration for new ß-lactam/ß-lactamase inhibitors so that they are earlier in a patient's treatment course.

Antimicrobial stewardship and antibiograms: importance of moving beyond traditional antibiograms.

The rapid evolution of resistance, particularly among Gram-negative bacteria, requires appropriate identification of patients at risk followed by administration of appropriate empiric antibiotic therapy. A primary tenet of antimicrobial stewardship programs (ASPs) is the establishment of empiric antibiotic recommendations for commonly encountered infections. An important tool in providing empiric antibiotic therapy recommendations is the use of an antibiogram. While the majority of institutions use a traditional antibiogram, ASPs have an opportunity to enhance antibiogram data. The authors provide the rationale for why ASPs should implement alternative antibiograms, and the importance of incorporating an antibiogram into clinical decision support systems with the goal of providing effective empiric antibiotic therapy.

Comparison of method-specific vancomycin minimum inhibitory concentration values and their predictability for treatment outcome of meticillin-resistant Staphylococcus aureus (MRSA) infections.

The objectives of this study were to examine the predictive value of method-specific vancomycin (VAN) minimum inhibitory concentration (MIC) results on treatment outcomes of meticillin-resistant Staphylococcus aureus (MRSA) infections. VAN MIC values for MRSA strains were determined using Etest, VITEK-1, MicroScan (MScan) and broth microdilution (BMD), with additional screening for heterogeneous glycopeptide-intermediate S. aureus (hGISA) phenotype. Patients' charts were reviewed for outcome correlation. Performance characteristics of method-specific VAN MICs in predicting outcome were compared. Most (76%) of the 92 strains tested caused pneumonia or bacteraemia. The majority of strains tested (>70%) had a VAN MIC >1mg/L by Etest or MScan compared with 41% by Vitek and 7% by BMD. Agreement between test methods for high versus low MICs (>1mg/L vs. < or = 1mg/L) ranged from 36% to 71%. High versus low VAN MICs by Etest differentiated response of invasive strains to VAN. Performance characteristics (sensitivity/specificity/positive predictive value/negative predictive value) were: Etest, 55/81/89/38%; and Vitek, 56/62/81/32/%, respectively. Eight strains (9%) demonstrated a hGISA phenotype; more yielded high MICs by Etest, MScan and Vitek than BMD (87%, 87% and 75% vs. 50%). In conclusion, VAN MIC testing methods produce highly variable results. The Etest method appears to be relatively more reliable in predicting treatment response and yielded higher MICs for strains with a hGISA phenotype.

High-dose vancomycin therapy for methicillin-resistant Staphylococcus aureus infections: efficacy and toxicity.

BACKGROUND: Vancomycin hydrochloride treatment failure for infections caused by susceptible methicillin-resistant Staphylococcus aureus (MRSA) strains with high minimum inhibitory concentration (MIC) has prompted recent guidelines to recommend a higher vancomycin target trough of 15 to 20 microg/mL. METHODS: A prospective cohort study of adult patients infected with MRSA was performed to determine the distribution of vancomycin MIC and treatment outcomes with vancomycin doses targeting an unbound trough of at least 4 times the MIC. The microbiology laboratory computer records were used to identify all patients from whom MRSA was isolated from August 1, 2004, through June 30, 2005. Primary outcome measures were clinical response, mortality, and nephrotoxicity. Patients were placed into subgroups based on target trough attainment and high vs low vancomycin MIC (>/=2 vs <2 microg/mL) for efficacy and high vs low trough (>/=15 vs <15 microg/mL) for nephrotoxicity analyses. RESULTS: Of the 95 patients in the study, 51 (54%) were infected with high-MIC strains and had pneumonia (77%) and/or bacteremia. An initial response rate of 74% was achieved if the target trough was attained irrespective of MIC. However, despite achieving the target trough, the high-MIC group had lower end-of-treatment responses (24/39 [62%] vs 34/40 [85%]; P = .02) and higher infection-related mortality (11/51 [24%] vs 4/44 [10%]; P=.16) compared with the low-MIC group. High MIC (P = .03) and Acute Physiology and Chronic Health Evaluation II score (P = .009) were independent predictors of poor response in multivariate analysis. Nephrotoxicity occurred only in the high-trough group (11/63 [12%]), significantly predicted by concomitant therapy with other nephrotoxic agents. CONCLUSIONS: High prevalence of clinical MRSA strains with elevated vancomycin MIC (2 microg/mL) requires aggressive empirical vancomycin dosing to achieve a trough greater than 15 microg/mL. Combination or alternative therapy should be considered for invasive infections caused by these strains.