Anusha Krishnadasan

Comparison of Staphylococcus aureus From Skin and Soft-Tissue Infections in US Emergency Department Patients, 2004 and 2008

BACKGROUND In the past decade, new methicillin-resistant Staphylococcus aureus (MRSA) strains have emerged as a predominant cause of community-associated skin and soft-tissue infections (SSTIs). Little information exists regarding trends in MRSA prevalence and molecular characteristics or regarding antimicrobial susceptibility profiles of S. aureus isolates. METHODS We enrolled adults with acute, purulent SSTIs presenting to a US network of 12 emergency departments during August 2008. Cultures and clinical information were collected. S. aureus isolates were characterized by antimicrobial susceptibility testing, pulsed-field gel electrophoresis, and toxin genes detection. The prevalence of S. aureus and MRSA and isolate genetic characteristics and susceptibilities were compared with those from a similar study conducted in August 2004. RESULTS The prevalence of MRSA was 59% among all SSTIs during both study periods; however, the prevalence by site varied less in 2008 (38%-84%), compared with 2004 (15%-74%). Pulsed-field type USA300 continued to account for almost all MRSA isolates (98%). Susceptibility to trimethoprim-sulfamethoxazole, clindamycin, and tetracycline among MRSA isolates remained greater than 90% in 2008. A higher proportion of MRSA infections were treated with an agent to which the infecting isolate was susceptible in vitro in 2008 (97%), compared with 2004 (57%). CONCLUSIONS Similar to 2004, MRSA remained the most common identifiable cause of purulent SSTIs among patients presenting to a network of US emergency departments in 2008. The infecting MRSA isolates continued to be predominantly pulsed-field type USA300 and susceptible to recommended non-β-lactam oral agents. Clinician prescribing practices have shifted from MRSA-inactive to MRSA-active empirical antimicrobial regimens.

Prevalence and Risk Factor Analysis of Trimethoprim-Sulfamethoxazole— and Fluoroquinolone-Resistant Escherichia coli Infection among Emergency Department Patients with Pyelonephritis

BACKGROUND High rates of resistance to trimethoprim-sulfamethoxazole (TMP-SMX) among uropathogenic Escherichia coli are recognized, and concerns exist about emerging fluoroquinolone resistance. METHODS Adults presenting to 11 US emergency departments with (1) flank pain and/or costovertebral tenderness, (2) temperature >38 degrees C, and (3) a presumptive diagnosis of pyelonephritis were enrolled; patients for whom 1 uropathogen grew on culture were analyzed. Epidemiologic and clinical data were collected at the time of care. The prevalence of E. coli in vitro antibiotic resistance and risk factors associated with TMP-SMX-resistant E. coli infection were determined. RESULTS Among 403 women with uncomplicated pyelonephritis caused by E. coli, the mean site rate of E. coli resistance to TMP-SMX was 24% (range, 13%-45%). Mean site rates of E. coli resistance to ciprofloxacin and levofloxacin were 1% and 3%, respectively. Only TMP-SMX exposure within 2 days before presentation and Hispanic ethnicity were associated with E. coli resistance to TMP-SMX (compared with resistance rates of approximately 20% among women lacking these risk factors); antibiotic exposure within 3-60 days before presentation, health care setting exposure within 30 days before presentation, history of urinary tract infections, and age >55 years were not associated with E. coli resistance to TMP-SMX. Among 207 patients with complicated pyelonephritis, mean site rates of E. coli resistance to ciprofloxacin and levofloxacin were 5% and 6%, respectively. CONCLUSIONS These results suggest that the prevalence of TMP-SMX-resistant infection among patients with uncomplicated pyelonephritis is > or =20% in many areas of the United States, and risk stratification cannot identify patients at low risk of infection. Rates of fluoroquinolone-resistant E. coli infection appear to be low among patients with uncomplicated pyelonephritis but higher among those with complicated infections. Fluoroquinolones should remain to be the preferred empirical treatment for women with uncomplicated pyelonephritis.

Prevalence of Methicillin-Resistant Staphylococcus aureus as an Etiology of Community-Acquired Pneumonia

BACKGROUND Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of skin infections. Recent case series describe severe community-acquired pneumonia (CAP) caused by MRSA, but the prevalence and risk factors are unknown. METHODS We prospectively enrolled adults hospitalized with CAP from 12 university-affiliated emergency departments during the winter-spring of 2006 and 2007. Clinical information and culture results were collected, and factors associated with MRSA were assessed. RESULTS Of 627 patients, 595 (95%) had respiratory (50%) and/or blood cultures (92%) performed. A pathogen was identified in 102 (17%); MRSA was identified in 14 (2.4%; range by site, 0%-5%) patients and in 5% of patients admitted to the intensive care unit. Two (14%) MRSA pneumonia patients died. All 9 MRSA isolates tested were pulsed-field type USA300. Features significantly associated with isolation of MRSA (as compared with any other or no pathogen) included patient history of MRSA; nursing home admission in the previous year; close contact in the previous month with someone with a skin infection; multiple infiltrates or cavities on chest radiograph; and comatose state, intubation, receipt of pressors, or death in the emergency department. CONCLUSIONS Methicillin-resistant Staphylococcus aureus remains an uncommon cause of CAP. Detection of MRSA was associated with more severe clinical presentation.

Trimethoprim–Sulfamethoxazole versus Placebo for Uncomplicated Skin Abscess

BACKGROUND U.S. emergency department visits for cutaneous abscess have increased with the emergence of methicillin-resistant Staphylococcus aureus (MRSA). The role of antibiotics for patients with a drained abscess is unclear. METHODS We conducted a randomized trial at five U.S. emergency departments to determine whether trimethoprim-sulfamethoxazole (at doses of 320 mg and 1600 mg, respectively, twice daily, for 7 days) would be superior to placebo in outpatients older than 12 years of age who had an uncomplicated abscess that was being treated with drainage. The primary outcome was clinical cure of the abscess, assessed 7 to 14 days after the end of the treatment period. RESULTS The median age of the participants was 35 years (range, 14 to 73); 45.3% of the participants had wound cultures that were positive for MRSA. In the modified intention-to-treat population, clinical cure of the abscess occurred in 507 of 630 participants (80.5%) in the trimethoprim-sulfamethoxazole group versus 454 of 617 participants (73.6%) in the placebo group (difference, 6.9 percentage points; 95% confidence interval [CI], 2.1 to 11.7; P=0.005). In the per-protocol population, clinical cure occurred in 487 of 524 participants (92.9%) in the trimethoprim-sulfamethoxazole group versus 457 of 533 participants (85.7%) in the placebo group (difference, 7.2 percentage points; 95% CI, 3.2 to 11.2; P<0.001). Trimethoprim-sulfamethoxazole was superior to placebo with respect to most secondary outcomes in the per-protocol population, resulting in lower rates of subsequent surgical drainage procedures (3.4% vs. 8.6%; difference, -5.2 percentage points; 95% CI, -8.2 to -2.2), skin infections at new sites (3.1% vs. 10.3%; difference, -7.2 percentage points; 95% CI, -10.4 to -4.1), and infections in household members (1.7% vs. 4.1%; difference, -2.4 percentage points; 95% CI, -4.6 to -0.2) 7 to 14 days after the treatment period. Trimethoprim-sulfamethoxazole was associated with slightly more gastrointestinal side effects (mostly mild) than placebo. At 7 to 14 days after the treatment period, invasive infections had developed in 2 of 524 participants (0.4%) in the trimethoprim-sulfamethoxazole group and in 2 of 533 participants (0.4%) in the placebo group; at 42 to 56 days after the treatment period, an invasive infection had developed in 1 participant (0.2%) in the trimethoprim-sulfamethoxazole group. CONCLUSIONS In settings in which MRSA was prevalent, trimethoprim-sulfamethoxazole treatment resulted in a higher cure rate among patients with a drained cutaneous abscess than placebo. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00729937.).

Estimated Effects of Hydrazine Exposure on Cancer Incidence and Mortality in Aerospace Workers

Background: Animal studies suggest that hydrazine is a lung carcinogen, but human studies have been rare, rather small, and limited to cancer mortality. Methods: We examined cancer mortality and incidence in a cohort of aerospace workers with varying exposure to hydrazine contained in rocket fuels—extending previous mortality follow-up from 1994 to 2001 and investigating cancer incidence for the period 1988–2000 using population-registry data. We newly estimated hydrazine effects adjusting for occupational exposures to other carcinogens assessed through a job-exposure matrix. Rate-ratio estimates were derived from Cox proportional hazards and random-effects models using time-dependent exposure measures for hydrazine adjusting for trichloroethylene, polycyclic aromatic hydrocarbons, benzene, and mineral oil exposures. Results: Exposure to hydrazine was positively associated with lung cancer incidence (estimated rate ratio for high vs low exposure with 20-year lag = 2.5; 95% confidence interval = 1.3–4.9) and with colorectal cancer incidence (2.2; 1.0–4.6). Dose–response associations were observed for both outcomes; similar associations were found for lung cancer mortality but not for colorectal cancer mortality. Effect estimates for cancers of the pancreas, blood and lymph system, and kidneys were based on small numbers rendering our analyses uninformative, and patterns considering exposure levels and lags were inconsistent. Use of random-effect models did not change our results. Conclusions: The findings reported here are consistent with our previous results for lung cancer mortality; our new results suggest that exposure to hydrazine increases the risk of incident lung cancers. We also found, for the first time, an increased risk of colon cancers. Results for other cancer sites are inconclusive.

Staphylococcus aureus Colonization and Strain Type at Various Body Sites among Patients with a Closed Abscess and Uninfected Controls at U.S. Emergency Departments

ABSTRACT Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is a prevalent cause of skin and soft tissue infections (SSTI), but the association between CA-MRSA colonization and infection remains uncertain. We studied the carriage frequency at several body sites and the diversity of S. aureus strains from patients with and without SSTI. Specimens from the nares, throat, rectum, and groin of case subjects with a closed skin abscess (i.e., without drainage) and matched control subjects without a skin infection (n = 147 each) presenting to 10 U.S. emergency departments were cultured using broth enrichment; wound specimens were cultured from abscess cases. Methicillin resistance testing and spa typing were performed for all S. aureus isolates. S. aureus was found in 85/147 (57.8%) of abscesses; 49 isolates were MRSA, and 36 were methicillin-susceptible S. aureus (MSSA). MRSA colonization was more common among cases (59/147; 40.1%) than among controls (27/147; 18.4%) overall (P < 0.001) and at each body site; no differences were observed for MSSA. S. aureus-infected subjects were usually (75/85) colonized with the infecting strain; among MRSA-infected subjects, this was most common in the groin. The CC8 lineage accounted for most of both infecting and colonizing isolates, although more than 16 distinct strains were identified. Nearly all MRSA infections were inferred to be USA300. There was more diversity among colonizing than infecting isolates and among those isolated from controls versus cases. CC8 S. aureus is a common colonizer of persons with and without skin infections. Detection of S. aureus colonization, and especially MRSA, may be enhanced by extranasal site culture.

Introduction of Rapid Methicillin-Resistant Staphylococcus aureus Polymerase Chain Reaction Testing and Antibiotic Selection Among Hospitalized Patients With Purulent Skin Infections

Introduction of a rapid methicillin-resistant Staphylococcus aureus (MRSA) polymerase chain reaction assay, with physician education and pharmacist guidance, did not significantly reduce excessive empiric prescription of MRSA-active antibiotics despite the tests accuracy and potential to substantially reduce inappropriate antibiotic use.

Decision Instrument for the Isolation of Pneumonia Patients With Suspected Pulmonary Tuberculosis Admitted Through US Emergency Departments

STUDY OBJECTIVE Many patients with pneumonia are admitted to respiratory isolation for possible tuberculosis (TB), but most do not have active TB. We created a decision instrument to predict which pneumonia patients do not need admission to a TB isolation bed. METHODS The design was a prospective case series conducted in 11 university-affiliated, urban, US emergency departments (EDs) (EMERGEncy ID NET). Participants were patients admitted to the hospital through the ED with a diagnosis of pneumonia or suspected TB. The main outcome measure was derivation and validation of a sensitive decision instrument to identify patients not having TB (and not requiring isolation) according to clinical data and chest radiographs. RESULTS Of 5,079 pneumonia patients, 224 (4.4%) had pulmonary TB according to sputum cultures or tissue staining. The instrument derived to predict which patients did not have pulmonary TB included no TB history or previous positive tuberculin skin test result, nonimmigrant, not homeless, not recently incarcerated, no recent weight loss, and no apical infiltrate or cavitary lesion on plain chest radiograph. When tested on the validation subgroup, the decision instrument exhibited a negative predictive value of 99.7% (95% confidence interval [CI] 99.1% to 99.9%), and a sensitivity of 96.4% (95% CI 91.1% to 99.0%). CONCLUSION A decision instrument can accurately predict which patients with pneumonia do not require admission to TB isolation rooms.

Fluoroquinolone-Resistant and Extended-Spectrum beta-Lactamase Producing Escherichia coli Infections in Patients with Pyelonephritis, United States

Prevalence of fluoroquinolone resistance now exceeds treatment guideline thresholds for alternative antimicrobial drug strategies.

Factors Associated with Decision to Hospitalize Emergency Department Patients with Skin and Soft Tissue Infection

Introduction Emergency department (ED) hospitalizations for skin and soft tissue infection (SSTI) have increased, while concern for costs has grown and outpatient parenteral antibiotic options have expanded. To identify opportunities to reduce admissions, we explored factors that influence the decision to hospitalize an ED patient with a SSTI. Methods We conducted a prospective study of adults presenting to 12 U.S. EDs with a SSTI in which physicians were surveyed as to reason(s) for admission, and clinical characteristics were correlated with disposition. We employed chi-square binary recursive partitioning to assess independent predictors of admission. Serious adverse events were recorded. Results Among 619 patients, median age was 38.7 years. The median duration of symptoms was 4.0 days, 96 (15.5%) had a history of fever, and 46 (7.5%) had failed treatment. Median maximal length of erythema was 4.0cm (IQR, 2.0–7.0). Upon presentation, 39 (6.3%) had temperature >38°C, 81 (13.1%) tachycardia, 35 (5.7%), tachypnea, and 5 (0.8%) hypotension; at the time of the ED disposition decision, these findings were present in 9 (1.5%), 11 (1.8%), 7 (1.1%), and 3 (0.5%) patients, respectively. Ninety-four patients (15.2%) were admitted, 3 (0.5%) to the intensive care unit (ICU). Common reasons for admission were need for intravenous antibiotics in 80 (85.1%; the only reason in 41.5%), surgery in 23 (24.5%), and underlying disease in 11 (11.7%). Hospitalization was significantly associated with the following factors in decreasing order of importance: history of fever (present in 43.6% of those admitted, and 10.5% discharged; maximal length of erythema >10cm (43.6%, 11.3%); history of failed treatment (16.1%, 6.0%); any co-morbidity (61.7%, 27.2%); and age >65 years (5.4%, 1.3%). Two patients required amputation and none had ICU transfer or died. Conclusion ED SSTI patients with fever, larger lesions, and co-morbidities tend to be hospitalized, almost all to non-critical areas and rarely do they suffer serious complications. The most common reason for admission is administration of intravenous antibiotics, which is frequently the only reason for hospitalization. With the increasing outpatient intravenous antibiotic therapy options, these results suggest that many hospitalized patients with SSTI could be managed safely and effectively as outpatients.