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Bacterial clonal diagnostics as a tool for evidence-based empiric antibiotic selection.

ABSTRACT: Despite the known clonal distribution of antibiotic resistance in many bacteria, empiric (pre-culture) antibiotic selection still relies heavily on species-level cumulative antibiograms, resulting in overuse of broad-spectrum agents and excessive antibiotic/pathogen mismatch. Urinary tract infections (UTIs), which account for a large share of antibiotic use, are caused predominantly by Escherichia coli, a highly clonal pathogen. In an observational clinical cohort study of urgent care patients with suspected UTI, we assessed the potential for E. coli clonal-level antibiograms to improve empiric antibiotic selection. A novel PCR-based clonotyping assay was applied to fresh urine samples to rapidly detect E. coli and the urine strain's clonotype. Based on a database of clonotype-specific antibiograms, the acceptability of various antibiotics for empiric therapy was inferred using a 20%, 10%, and 30% allowed resistance threshold. The test's performance characteristics and possible effects on prescribing were assessed. The rapid test identified E. coli clonotypes directly in patients' urine within 25-35 minutes, with high specificity and sensitivity compared to culture. Antibiotic selection based on a clonotype-specific antibiogram could reduce the relative likelihood of antibiotic/pathogen mismatch by ? 60%. Compared to observed prescribing patterns, clonal diagnostics-guided antibiotic selection could safely double the use of trimethoprim/sulfamethoxazole and minimize fluoroquinolone use. In summary, a rapid clonotyping test showed promise for improving empiric antibiotic prescribing for E. coli UTI, including reversing preferential use of fluoroquinolones over trimethoprim/sulfamethoxazole. The clonal diagnostics approach merges epidemiologic surveillance, antimicrobial stewardship, and molecular diagnostics to bring evidence-based medicine directly to the point of care.

SUBMITTER: Tchesnokova V

PROVIDER: S-EPMC5369764 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Bacterial clonal diagnostics as a tool for evidence-based empiric antibiotic selection.

Tchesnokova Veronika V Avagyan Hovhannes H Rechkina Elena E Chan Diana D Muradova Mariya M Haile Helen Ghirmai HG Radey Matthew M Weissman Scott S Riddell Kim K Scholes Delia D Johnson James R JR Sokurenko Evgeni V EV

PloS one 20170328 3

Despite the known clonal distribution of antibiotic resistance in many bacteria, empiric (pre-culture) antibiotic selection still relies heavily on species-level cumulative antibiograms, resulting in overuse of broad-spectrum agents and excessive antibiotic/pathogen mismatch. Urinary tract infections (UTIs), which account for a large share of antibiotic use, are caused predominantly by Escherichia coli, a highly clonal pathogen. In an observational clinical cohort study of urgent care patients w ...[more]

PMID: 28350870

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Project description:Acutely swollen or painful joints are common complaints in the emergency department (ED). Septic arthritis in adults is a challenging diagnosis, but prompt differentiation of a bacterial etiology is crucial to minimize morbidity and mortality.The objective was to perform a systematic review describing the diagnostic characteristics of history, physical examination, and bedside laboratory tests for nongonococcal septic arthritis. A secondary objective was to quantify test and treatment thresholds using derived estimates of sensitivity and specificity, as well as best-evidence diagnostic and treatment risks and anticipated benefits from appropriate therapy.Two electronic search engines (PUBMED and EMBASE) were used in conjunction with a selected bibliography and scientific abstract hand search. Inclusion criteria included adult trials of patients presenting with monoarticular complaints if they reported sufficient detail to reconstruct partial or complete 2 × 2 contingency tables for experimental diagnostic test characteristics using an acceptable criterion standard. Evidence was rated by two investigators using the Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS). When more than one similarly designed trial existed for a diagnostic test, meta-analysis was conducted using a random effects model. Interval likelihood ratios (LRs) were computed when possible. To illustrate one method to quantify theoretical points in the probability of disease whereby clinicians might cease testing altogether and either withhold treatment (test threshold) or initiate definitive therapy in lieu of further diagnostics (treatment threshold), an interactive spreadsheet was designed and sample calculations were provided based on research estimates of diagnostic accuracy, diagnostic risk, and therapeutic risk/benefits.The prevalence of nongonococcal septic arthritis in ED patients with a single acutely painful joint is approximately 27% (95% confidence interval [CI] = 17% to 38%). With the exception of joint surgery (positive likelihood ratio [+LR] = 6.9) or skin infection overlying a prosthetic joint (+LR = 15.0), history, physical examination, and serum tests do not significantly alter posttest probability. Serum inflammatory markers such as white blood cell (WBC) counts, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) are not useful acutely. The interval LR for synovial white blood cell (sWBC) counts of 0 × 10(9)-25 × 10(9)/L was 0.33; for 25 × 10(9)-50 × 10(9)/L, 1.06; for 50 × 10(9)-100 × 10(9)/L, 3.59; and exceeding 100 × 10(9)/L, infinity. Synovial lactate may be useful to rule in or rule out the diagnosis of septic arthritis with a +LR ranging from 2.4 to infinity, and negative likelihood ratio (-LR) ranging from 0 to 0.46. Rapid polymerase chain reaction (PCR) of synovial fluid may identify the causative organism within 3 hours. Based on 56% sensitivity and 90% specificity for sWBC counts of >50 × 10(9)/L in conjunction with best-evidence estimates for diagnosis-related risk and treatment-related risk/benefit, the arthrocentesis test threshold is 5%, with a treatment threshold of 39%.Recent joint surgery or cellulitis overlying a prosthetic hip or knee were the only findings on history or physical examination that significantly alter the probability of nongonococcal septic arthritis. Extreme values of sWBC (>50 × 10(9)/L) can increase, but not decrease, the probability of septic arthritis. Future ED-based diagnostic trials are needed to evaluate the role of clinical gestalt and the efficacy of nontraditional synovial markers such as lactate.

Dataset Information

Bacterial clonal diagnostics as a tool for evidence-based empiric antibiotic selection.

Publications

Bacterial clonal diagnostics as a tool for evidence-based empiric antibiotic selection.

Similar Datasets

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