OBJECTIVES Quantify the prevalence, measure the severity, and describe treatment patterns in patients who present to medical clinics in Texas with community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) skin and soft-tissue infections (SSTI). METHODS Ten primary care clinics participated in this prospective, community-based study. Clinicians consented patients and collected clinical information, pictures, and wound swabs; data were processed centrally. MRSASelect™ was used for identification. Susceptibilities were determined via Etest®. RESULTS Overall, 73/119 (61%) patients presenting with SSTIs meeting eligibility requirements had CA-MRSA. Among these, 49% were male, 79% were Hispanic, and 30% had diabetes. Half (56%) of the lesions were ≥ 5 cm in diameter. Most patients had abscesses (82%) and many reported pain scores of ≥ 7/10 (67%). Many presented with erythema (85%) or drainage (56%). Most received incision and drainage (I&D) plus an antibiotic (64%). Antibiotic monotherapy was frequently prescribed: trimethoprim-sulfamethoxazole (TMP-SMX) (78%), clindamycin (4%), doxycycline (2%), and mupirocin (2%). The rest received TMP-SMX in combination with other antibiotics. TMP-SMX was frequently administered as one double-strength tablet twice daily. Isolates were 93% susceptible to clindamycin and 100% susceptible to TMP-SMX, doxycycline, vancomycin, and linezolid. CONCLUSIONS We report a predominance of CA-MRSA SSTIs, favorable antibiotic susceptibilities, and frequent use of TMP-SMX in primary care clinics.

BackgroundPrevious studies have established a correlation between vancomycin troughs and nephrotoxicity. However, data are currently lacking regarding the effect of guideline-recommended weight-based dosing on nephrotoxicity in methicillin-resistant Staphylococcus aureus bacteremia (MRSAB).MethodsAdults who were at least 18 years of age with methicillin-resistant Staphylococcus aureus bacteremia and received of empiric vancomycin therapy for at least 48 hours (01/07/2002 and 30/06/2008) were included in this multicenter, retrospective cohort study. The association between guideline-recommended, weight-based vancomycin dosing (at least 15 mg/kg/dose) and nephrotoxicity (increase in serum creatinine (SCr) by more than 0.5 mg/dl or at least a 50% increase from baseline on at least two consecutive laboratory tests) was evaluated. Potential independent associations were evaluated using a multivariable general linear mixed-effect model.ResultsOverall, 23% of patients developed nephrotoxicity. Thirty-four percent of the 337 patients who met study criteria received weight-based dosing. The cohort was composed of 69% males with a median age of 55 years. The most common sources of MRSAB included skin/soft tissue (32%), catheter-related bloodstream bacteremia (20%), pulmonary (18%). Eighty-six percent of patients received twice daily dosing. Similar rates of nephrotoxicity were observed regardless of the receipt of guideline-recommended dosing (22% vs. 24%, OR 0.91 [95% CI 0.53-1.56]). This finding was confirmed in the multivariable analysis (OR 1.52 [95% CI 0.75-3.08]). Independent predictors of nephrotoxicity were (OR, 95% CI) vancomycin duration of greater than 15 days (3.36, 1.79-6.34), weight over 100 kg (2.74, 1.27-5.91), Pitt bacteremia score of 4 or greater (2.73, 1.29-5.79), vancomycin trough higher than 20 mcg/ml (2.36, 1.07-5.20), and age over 52 years (2.10, 1.08-4.08).ConclusionsOver one out of five patients in this study developed nephrotoxicity while receiving vancomycin for MRSAB. The receipt of guideline-recommended, weight-based vancomycin was not an independent risk factor for the development of nephrotoxicity.

BackgroundNo studies have evaluated the effect of guideline-recommended weight-based dosing on in-hospital mortality of patients with methicillin-resistant Staphylococcus aureus bacteremia.MethodsThis was a multicenter, retrospective, cohort study of patients with methicillin-resistant Staphylococcus aureus bacteremia receiving at least 48 hours of empiric vancomycin therapy between 01/07/2002 and 30/06/2008. We compared in-hospital mortality for patients treated empirically with weight-based, guideline-recommended vancomycin doses (at least 15 mg/kg/dose) to those treated with less than 15 mg/kg/dose. We used a general linear mixed multivariable model analysis with variables identified a priori through a conceptual framework based on the literature.ResultsA total of 337 patients who were admitted to the three hospitals were included in the cohort. One-third of patients received vancomycin empirically at the guideline-recommended dose. Guideline-recommended dosing was not associated with in-hospital mortality in the univariable (16% vs. 13%, OR 1.26 [95%CI 0.67-2.39]) or multivariable (OR 0.71, 95%CI 0.33-1.55) analysis. Independent predictors of in-hospital mortality were ICU admission, Pitt bacteremia score of 4 or greater, age 53 years or greater, and nephrotoxicity.ConclusionsEmpiric use of weight-based, guideline-recommended empiric vancomycin dosing was not associated with reduced mortality in this multicenter study.

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What is known and objective Few studies have evaluated the effect of vancomycin dosing on the health outcomes in geriatric patients. Data are needed to determine if higher vancomycin dosing strategies are more effective in geriatric patients and/or lead to excessive rates of adverse events. Methods This study used a subset of patients ages ≥ 65 years from a multicenter, retrospective, cohort study of methicillin resistant Staphylococcus aureus (MRSA) bacteremia. Patients received ≥ 48 hours of empiric vancomycin between 07/01/2002 and 06/30/2008. We compared the incidence of nephrotoxicity and in-hospital mortality in patients who received guideline-recommended dosing (at least 15 mg/kg/dose) to patients who received lower dosing. Multivariable generalized mixed effects models were constructed to determine independent risk factors for nephrotoxicity and in-hospital mortality. Results and discussion Half of the cohort (46% of 92 patients) received guideline-recommended dosing. Empiric use of weight-based dosing did increase the percentage of patients achieving a vancomycin trough ≥ 15 mg/L (57% vs. 42%). Nephrotoxicity occurred in 32% of patients and 26% died during their hospitalization. Guideline-recommended dosing was not associated with significant changes in nephrotoxicity (OR 1.03; 95% CI 0.38–2.82) or in-hospital mortality (OR 1.01; 95% CI 0.40–2.54) in the multivariable analysis. What is new and conclusion In this study of geriatric patients, guideline-recommended dosing was not associated with significant changes in nephrotoxicity or mortality. Since 40% of the patients who received guideline-recommended dosing failed to achieve a target vancomycin trough of ≥ 15 mg/L, future studies should focus on dosing strategies to increase target attainment rate.

The annual incidence of skin and soft tissue infections (SSTIs) has nearly tripled in the US since the early 1990s. Many purulent SSTIs in the community setting are caused by methicillin-resistant Staphylococcus aureus (MRSA). Incision and drainage (I&D) are indicated for most purulent MRSA infections; however, the use of adjunctive antibacterials is controversial. The objective of this study was to systematically evaluate studies that have investigated whether or not antibacterials provide added benefit to I&D alone for purulent MRSA SSTIs. We included articles from MEDLINE and The Cochrane Library that fulfilled the following criteria: (i) original research; (ii) English language; (iii) compared I&D alone versus I&D plus antibacterials for purulent MRSA SSTIs; and (iv) compared patient outcomes. We also reviewed the references of these articles to identify other relevant studies. Studies that solely examined paediatric patients were excluded. To facilitate cross-study comparison, we systematically evaluated the following study characteristics: (i) study design; (ii) patient population; (iii) comparator groups; (iv) sample size; (v) outcome measures; (vi) outcome definitions; (vii) duration of follow-up; and (viii) measurement and adjustment of potential confounding variables. Eleven studies, spanning more than 30 years, met inclusion criteria. Two of these were conducted prior to the emergence of MRSA in the community; another evaluated cephalexin versus placebo for MRSA. None of these found added benefit of adjunctive antibacterials. Four studies compared health outcomes between patients who received 'active' or 'appropriate' therapy and those who received 'inactive' or 'inappropriate' therapy after I&D for purulent MRSA SSTIs. Two of these studies found 'active' or 'appropriate' therapy to be beneficial, while two others did not. Four studies compared health outcomes between patients who received anti-MRSA antibacterials plus I&D with those who received alternative antibacterials plus I&D for purulent MRSA SSTIs. Three of these reported improved outcomes with anti-MRSA antibacterials, while another reported mixed findings. Presently, the bulk of the available evidence suggests anti-MRSA antibacterials provide added benefit to I&D alone for purulent MRSA SSTIs; however, the current evidence is limited to small, case-control, observational studies.

To the Editor: We thank Khawcharoenporn for his comments regarding our recent study involving patients with CA-MRSA skin and soft tissue infections (SSTIs). 1 This study includes a subgroup analysis of patients who received incision and drainage (I&D) alone versus I&D plus antibiotics (94% received trimethoprim-sulfamethoxazole or clindamycin). Retrospective, observational studies like ours are potentially subject to selection bias; however, a comparison of baseline characteristics revealed no significant differences in age, sex, Hispanic ethnicity, insurance status, diabetes, hypertension, hyperlipidemia, coronary artery disease, obesity, depression, HIV, hepatitis C, tobacco use, alcohol use, intravenous drug use, history of skin infection, or baseline pain score for patients who received I&D alone or I&D plus antibiotics. Nevertheless, unmeasured variables, including disease severity, could partially account for the outcomes differences we observed between these 2 groups. We could not determine disease severity retrospectively because of a lack of information regarding lesion characteristics like size, depth, and number. Novel severity scoring systems, such as the one developed by Khawcharoenporn and Tice 2 for cellulitis, potentially are useful for patient care and in clinical research. The challenge in applying such rules is that the requisite information (eg, white blood cell count) may not be part of the routine work-up for outpatients with SSTIs. Furthermore, there is a clear need to develop and validate such a rule among a cohort of patients with skin abscesses because these are a common type of CA-MRSA infection. 3 Khawcharoenporn also refers to a randomized, controlled trial by Rajendran et al. 4 This study is frequently cited as evidence that antibiotics are unnecessary in uncomplicated SSTIs. The study was actually a double-placebo trial because neither placebo nor cephalexin has activity against MRSA. Success rates were similar and high in both groups; therefore, the authors concluded that this study provides "strong evidence that antibiotics may be unnecessary after surgical drainage of uncomplicated skin and soft tissue abscesses caused by community strains of MRSA." We applaud the strong study design; however, the conclusion overstates the findings, given that MRSA is responsible for 60% of community-associated SSTIs and neither of the study arms included antibiotics with activity against CA-MRSA. 5

Background We have conducted previous studies in all hospitalized patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia to determine safety and effectiveness of guideline-recommended, weight-based dosing of vancomycin. In these studies, we observed that severely ill patients (Pitt bacteremia score ≥ 4 or ICU patients) were at an increased risk of mortality and/or nephrotoxicity. Therefore, we conducted a subanalysis of the effect of guideline-recommended vancomycin dosing on in-hospital mortality and nephrotoxicity in intensive care unit (ICU) patients with MRSA bacteremia. Methods This multicenter, retrospective, cohort study was conducted in a subset of ICU patients from a previous MRSA bacteremia study. Patients were ≥18 years old and received ≥48 hours of empiric vancomycin from 07/01/2002 to 06/30/2008. We compared the incidence of nephrotoxicity and in-hospital mortality in patients that received guideline-recommended dosing (at least 15 mg/kg/dose) to patients that received non-guideline-recommended dosing of vancomycin. Multivariable generalized linear mixed-effects models were constructed to determine independent risk factors for in-hospital mortality and nephrotoxicity. Results Guideline-recommended dosing was received by 34% of patients (n=137). Nephrotoxicity occurred in 35% of patients receiving guideline-recommended dosing and 39% receiving non-guideline-recommended dosing (p=0.67). In-hospital mortality rate was 24% among patients who received guideline-recommended dosing compared with 31% for non-guideline-recommended dosing (p=0.40). Guideline-recommended dosing was not associated with nephrotoxicity (OR 1.10; 95% CI 0.43–2.79) or in-hospital mortality (OR 0.54; 95% CI 0.22–1.36) in the multivariable analysis. Conclusions Guideline-recommended dosing of vancomycin in ICU patients with MRSA bacteremia is not significantly associated with nephrotoxicity or in-hospital mortality. However, the 7% absolute difference for in-hospital mortality suggests larger studies are needed.