Criteria for reducing unnecessary testing for herpes simplex virus, varicella-zoster virus, cytomegalovirus, and enterovirus in cerebrospinal fluid samples from adults.

Excessive utilization of laboratory diagnostic testing leads to increased health care costs. We evaluated criteria to reduce unnecessary nucleic acid amplification testing (NAAT) for viral pathogens in cerebrospinal fluid (CSF) samples from adults. This is a single-center split retrospective observational study with a screening cohort from 2008 to 2012 and a validation cohort from 2013. Adults with available results for herpes simplex virus 1/2 (HSV-1/2), varicella-zoster virus (VZV), cytomegalovirus (CMV), or enterovirus (EV) NAAT with CSF samples between 2008 and 2013 were included (n = 10,917). During this study, 1.3% (n = 140) of viral NAAT studies yielded positive results. The acceptance criteria of >10 nucleated cells/µl in the CSF of immunocompetent subjects would have reduced HSV-1/2, VZV, CMV, and EV testing by 63%, 50%, 44%, and 51%, respectively, from 2008 to 2012. When these criteria were applied to the 2013 validation data set, 54% of HSV-1/2, 57% of VZV, 35% of CMV, and 56% of EV tests would have been cancelled. No clinically significant positive tests would have been cancelled in 2013 with this approach. The introduction of a computerized order entry set was associated with increased test requests, suggesting that computerized order sets may contribute to unnecessary testing. Acceptance criteria of >10 nucleated cells/µl in the CSF of immunocompetent adults for viral CSF NAAT assays would increase clinical specificity and preserve sensitivity, resulting in significant cost savings. Implementation of these acceptance criteria led to a 46% reduction in testing during a limited follow-up period.

Clostridium difficile ribotype diversity at six health care institutions in the United States.

Capillary-based PCR ribotyping was used to quantify the presence/absence and relative abundance of 98 Clostridium difficile ribotypes from clinical cases of disease at health care institutions in six states of the United States. Regionally important ribotypes were identified, and institutions in close proximity did not necessarily share more ribotype diversity than institutions that were farther apart.

Impact of clinical symptoms on interpretation of diagnostic assays for Clostridium difficile infections.

Asymptomatic Clostridium difficile colonization is common in hospitalized patients. Existing C. difficile assay comparisons lack data on severity of diarrhea or patient outcomes, limiting the ability to interpret their results in regard to the diagnosis of C. difficile infection (CDI). The objective of this study was to measure how including patient presentation with the C. difficile assay result impacted assay performance to diagnose CDI. Stool specimens from 150 patients that met inclusion and exclusion criteria were selected. Nine methods to detect C. difficile in stool were evaluated. All patients were interviewed prospectively to assess diarrhea severity. We then assessed how different reference standards, with and without the inclusion of patient presentation, impact the sensitivity, specificity, and positive and negative predictive values of the assays to diagnose CDI. There were minimal changes in sensitivity; however, specificity was significantly lower for the assays Tox A/B II, C. diff Chek-60, BD GeneOhm Cdiff, Xpert C. difficile, and Illumigene C. difficile and for toxigenic culture (P was <0.01 for all except Tox A/B II from fresh stool, for which the P value was 0.016) when the reference standard was recovery of toxigenic C. difficile from stool plus the presence of clinically significant diarrhea compared to when the reference standard was having at least four assays positive while ignoring diarrhea severity. There were 15 patients whose assay result was reported as negative but subsequently found to be positive by at least four assays in the comparison. None suffered from any CDI-related adverse events. In conclusion, clinical presentation is important when interpreting C. difficile diagnostic assays.

Impact of previous antibiotic therapy on outcome of Gram-negative severe sepsis.

OBJECTIVE: To determine whether exposure to antimicrobial agents in the previous 90 days resulted in decreased bacterial susceptibility and increased hospital mortality in patients with severe sepsis or septic shock attributed to Gram-negative bacteremia. DESIGN: A retrospective cohort study of hospitalized patients (January 2002 to December 2007). SETTING: Barnes-Jewish Hospital, a 1200-bed urban teaching hospital. PATIENTS: Seven hundred fifty-four consecutive patients with Gram-negative bacteremia complicated by severe sepsis or septic shock. INTERVENTIONS: Data abstraction from computerized medical records. MEASUREMENTS AND MAIN RESULTS: Escherichia coli (30.8%), Klebsiella pneumoniae (23.2%), and Pseudomonas aeruginosa (17.6%) were the most common isolates from blood cultures. Three hundred ten patients (41.1%) had recent antibiotic exposure. Cefepime was the most common agent with previous exposure (50.0%) followed by ciprofloxacin (32.6%) and imipenem or meropenem (28.7%). Patients with prior antibiotic exposure had significantly higher rates of resistance to cefepime (29.0% vs. 7.0%), piperacillin/tazobactam (31.9% vs. 11.5%), carbapenems (20.0% vs. 2.5%), ciprofloxacin (39.7% vs. 17.6%), and gentamicin (26.1% vs. 7.9%) (p < .001 for all comparisons). Patients with recent antibiotic exposure had greater inappropriate initial antimicrobial therapy (45.4% vs. 21.2%; p < .001) and hospital mortality (51.3% vs. 34.0%; p < .001) compared with patients without recent antibiotic exposure. Multivariate logistic regression analysis demonstrated that recent antibiotic exposure was independently associated with hospital mortality (adjusted odds ratio, 1.70; 95% confidence interval, 1.41-2.06; p = .005). Other variables independently associated with hospital mortality included use of vasopressors, infection resulting from P. aeruginosa, inappropriate initial antimicrobial therapy, increasing Acute Physiology and Chronic Health Evaluation II scores, and the number of acquired organ failures. CONCLUSIONS: Recent antibiotic exposure is associated with increased hospital mortality in Gram-negative bacteremia complicated by severe sepsis or septic shock. Clinicians caring for patients with severe sepsis or septic shock should consider recent antibiotic exposure when formulating empiric antimicrobial regimens for suspected Gram-negative bacterial infection.

Stenotrophomonas maltophilia intestinal colonization in hospitalized oncology patients with diarrhea.

A 6-week surveillance study was performed to determine the prevalence of Stenotrophomonas maltophilia intestinal colonization among patients hospitalized in an oncology unit who developed diarrhea. Ninety-two stool samples obtained from 41 patients were cultured, and 4 patients (4 [9.5%] of 41 patients) had cultures that were positive for S. maltophilia. After controlling for duration of diarrhea, patients colonized with S. maltophilia had received a greater number of different types of antibiotics than noncolonized patients (5 vs. 3 different drugs; P=.04).

Discontinuation of reflex testing of stool samples for vancomycin-resistant enterococci resulted in increased prevalence.

Discontinuation of reflex testing of stool submitted for Clostridium difficile testing for vancomycin-resistant enterococci (VRE) led to an increase in the number of patients with healthcare-associated VRE bacteremia and bacteriuria (0.21 vs 0.36 cases per 1,000 patient-days; P<.01). Cost-benefit analysis showed reflex screening and isolation of VRE reduced hospital costs.

Acanthamoeba keratitis: the persistence of cases following a multistate outbreak.

PURPOSE: To describe the trend of Acanthamoeba keratitis case reports following an outbreak and the recall of a multipurpose contact lens disinfection solution. Acanthamoeba keratitis is a serious eye infection caused by the free-living amoeba Acanthamoeba that primarily affects contact lens users. METHODS: A convenience sample of 13 ophthalmology centers and laboratories in the USA, provided annual numbers of Acanthamoeba keratitis cases diagnosed between 1999-2009 and monthly numbers of cases diagnosed between 2007-2009. Data on ophthalmic preparations of anti-Acanthamoeba therapies were collected from a national compounding pharmacy. RESULTS: Data from sentinel site ophthalmology centers and laboratories revealed that the yearly number of cases gradually increased from 22 in 1999 to 43 in 2003, with a marked increase beginning in 2004 (93 cases) that continued through 2007 (170 cases; p < 0.0001). The outbreak identified from these sentinel sites resulted in the recall of a contact lens disinfecting solution. There was a statistically significant (p ≤ 0.0001) decrease in monthly cases reported from 28 cases in June 2007 (following the recall) to seven cases in June 2008, followed by an increase (p = 0.0004) in reported cases thereafter; cases have remained higher than pre-outbreak levels. A similar trend was seen in prescriptions for Acanthamoeba keratitis chemotherapy. Cases were significantly more likely to be reported during summer than during other seasons. CONCLUSION: The persistently elevated number of reported cases supports the need to understand the risk factors and environmental exposures associated with Acanthamoeba keratitis. Further prevention efforts are needed to reduce the number of cases occurring among contact lens wearers.

Resistance to empiric antimicrobial treatment predicts outcome in severe sepsis associated with Gram-negative bacteremia.

BACKGROUND: Gram-negative bacteria are an important cause of severe sepsis. Recent studies have demonstrated reduced susceptibility of Gram-negative bacteria to currently available antimicrobial agents. METHODS: We performed a retrospective cohort study of patients with severe sepsis who were bacteremic with Pseudomonas aeruginosa, Acinetobacter species, or Enterobacteriaceae from 2002 to 2007. Patients were identified by the hospital informatics database and pertinent clinical data (demographics, baseline severity of illness, source of bacteremia, and therapy) were retrieved from electronic medical records. All patients were treated with antimicrobial agents within 12 hours of having blood cultures drawn that were subsequently positive for bacterial pathogens. The primary outcome was hospital mortality. RESULTS: A total of 535 patients with severe sepsis and Gram-negative bacteremia were identified. Hospital mortality was 43.6%, and 82 (15.3%) patients were treated with an antimicrobial regimen to which the causative pathogen was resistant. Patients infected with a resistant pathogen had significantly greater risk of hospital mortality (63.4% vs 40.0%; P < 0.001). In a multivariate analysis, infection with a pathogen that was resistant to the empiric antibiotic regimen, increasing APACHE II scores, infection with Pseudomonas aeruginosa, healthcare-associated hospital-onset infection, mechanical ventilation, and use of vasopressors were independently associated with hospital mortality. CONCLUSIONS: In severe sepsis attributed to Gram-negative bacteremia, initial treatment with an antibiotic regimen to which the causative pathogen is resistant was associated with increased hospital mortality. This finding suggests that rapid determination of bacterial susceptibility could influence treatment choices in patients with severe sepsis potentially improving their clinical outcomes.

Identification of a pseudo-outbreak of Clostridium difficile infection (CDI) and the effect of repeated testing, sensitivity, and specificity on perceived prevalence of CDI.

OBJECTIVE: To describe a pseudo-outbreak of Clostridium difficile infection (CDI) caused by a faulty toxin assay lot and to determine the effect of sensitivity, specificity, and repeated testing for C. difficile on perceived CDI burden, positive predictive value, and false-positive results. DESIGN: Outbreak investigation and criterion standard. PATIENTS: Patients hospitalized at a tertiary care hospital who had at least 1 toxin assay for detection of C. difficile performed during the period from July 1, 2004, through June 30, 2006. METHODS: The run control chart method and the chi(2) test were used to compare CDI rates and the proportion of positive test results before, during, and after the pseudo-outbreak. The effect of repeated testing was evaluated by using 3 hypothetical models with a sample of 10,000 patients and various assay sensitivity and specificity estimates. RESULTS: In November of 2005, the CDI rate at the hospital increased from 1.5 to 2.6 cases per 1,000 patient-days (P < .01), and the proportion of positive test results increased from 13.6% to 22.1% (P < .01). An investigation revealed a pseudo-outbreak caused by a faulty toxin assay lot. A decrease of only 1.2% in the specificity of the toxin assay would result in a 32% increase in perceived incidence of CDI at this institution. When calculated by use of the manufacturer's stated specificity and sensitivity and this institution's testing practices, the positive predictive value of the test decreased from 80.6% to 4.1% for patients who received 3 tests. CONCLUSION: Specificity is as important as sensitivity when testing for CDI. False-positive CDI cases can drain hospital resources and adversely affect patients. Repeated testing for C. difficile should be performed with caution.