Background. The occurrence of community-associated infections due to extended-spectrum β-lactamase (ESBL)-producing Escherichia coli has been recognized as a major clinical problem in Europe and other regions. Methods. We conducted a prospective observational study to examine the occurrence of community-associated infections due to ESBL-producing E. coli at centers in the United States. Five academic and community hospitals and their affiliated clinics participated in this study in 2009 and 2010. Sites of acquisition of the organisms (community-associated or healthcare-associated), risk factors, and clinical outcome were investigated. Screening for the global epidemic sequence type (ST) 131 and determination of the ESBL types was conducted by polymerase chain reaction and sequencing. Results. Of the 291 patients infected or colonized with ESBL-producing E. coli as outpatients or within 48 hours of hospitalization, 107 (36.8%) had community-associated infection (81.5% of which represented urinary tract infection), while the remainder had healthcare-associated infection. Independent risk factors for healthcare-associated infection over community-associated infection were the presence of cardiovascular disease, chronic renal failure, dementia, solid organ malignancy, and hospitalization within the previous 12 months. Of the community-associated infections, 54.2% were caused by the globally epidemic ST131 strain, and 91.3% of the isolates produced CTX-M-type ESBL. Conclusions. A substantial portion of community-onset, ESBL-producing E. coli infections now occur among patients without discernible healthcare-associated risk factors in the United States. This epidemiologic shift has implications for the empiric management of community-associated infection when involvement of E. coli is suspected.

The Clinical and Laboratory Standards Institute (CLSI) Subcommittee on Antimicrobial Susceptibility Testing (AST SC) is a volunteer-led, multidisciplinary consensus body that develops and publishes standards and guidelines (among other products) for antimicrobial susceptibility testing (AST) methods and results interpretation in the United States and internationally. The Subcommittee (SC) meets face-to-face twice yearly, and its working groups (WGs) are active throughout the year via teleconferences. All meetings are open to the public. Participants include clinical microbiologists, infectious disease (ID) pharmacists, and infectious disease physicians representing the health care professions, government, and industry. Individuals who work for a company with a primary financial dependency on drug sales cannot serve as voting members, and well-defined conflict of interest polices are in place. In addition to developing and updating susceptibility breakpoints, the SC develops and validates new testing methods, provides guidance on how results should be interpreted and applied, sets quality control ranges, and educates users through seminars, symposia, and webinars. Based on its work, the SC publishes print and electronic standards and guidelines, including an annual update, the Performance Standards for Antimicrobial Susceptibility Testing (M100). This commentary will describe the background, organization, functions, and operational processes of the AST SC.

No abstract

The increasing incidence of a variety of infections due to Staphylococcus aureus--and, especially, the expanding role of community-associated methicillin-resistant S. aureus (MRSA)--has led to emphasis on the need for safe and effective agents to treat both systemic and localized staphylococcal infections. Unlike most previously noted strains of health care-associated MRSA, community-acquired MRSA isolates are often susceptible to several non- beta -lactam drug classes, although they are usually not susceptible to macrolides. Several newer antimicrobial agents and a few older agents are available for treatment of systemic staphylococcal infections, but use may be limited by the relatively high cost of these agents or the need for parenteral administration. Inexpensive oral agents for treatment of localized, community-acquired MRSA infection include clindamycin, trimethoprim-sulfamethoxazole, and newer tetracyclines. Clindamycin has been used successfully to treat pneumonia and soft-tissue and musculoskeletal infections due to MRSA in adults and children. However, concern over the possibility of emergence of clindamycin resistance during therapy has discouraged some clinicians from prescribing that agent. Simple laboratory testing (e.g., the erythromycin-clindamycin "D-zone" test) can separate strains that have the genetic potential (i.e., the presence of erm genes) to become resistant during therapy from strains that are fully susceptible to clindamycin.

BackgroundThe use of antibiotics is the single most important driver in antibiotic resistance. Nevertheless, antibiotic overuse remains common. Decline in antibiotic prescribing in the United States coincided with the launch of national educational campaigns in the 1990s and other interventions, including the introduction of routine infant immunizations with the pneumococcal conjugate vaccine (PCV-7); however, it is unknown if these trends have been sustained through recent measurements.MethodsWe performed an analysis of nationally representative data from the Medical Expenditure Panel Surveys from 2000 to 2010. Trends in population-based prescribing were examined for overall antibiotics, broad-spectrum antibiotics, antibiotics for acute respiratory tract infections (ARTIs) and antibiotics prescribed during ARTI visits. Rates were reported for three age groups: children and adolescents (<18 years), adults (18 to 64 years), and older adults (≥65 years).ResultsAn estimated 1.4 billion antibiotics were dispensed over the study period. Overall antibiotic prescribing decreased 18% (risk ratio (RR) 0.82, 95% confidence interval (95% CI) 0.72 to 0.94) among children and adolescents, remained unchanged for adults, and increased 30% (1.30, 1.14 to 1.49) among older adults. Rates of broad-spectrum antibiotic prescriptions doubled from 2000 to 2010 (2.11, 1.81 to 2.47). Proportions of broad-spectrum antibiotic prescribing increased across all age groups: 79% (1.79, 1.52 to 2.11) for children and adolescents, 143% (2.43, 2.07 to 2.86) for adults and 68% (1.68, 1.45 to 1.94) for older adults. ARTI antibiotic prescribing decreased 57% (0.43, 0.35 to 0.52) among children and adolescents and 38% (0.62, 0.48 to 0.80) among adults; however, it remained unchanged among older adults. While the number of ARTI visits declined by 19%, patients with ARTI visits were more likely to receive an antibiotic (73% versus 64%; P <0.001) in 2010 than in 2000.ConclusionsAntibiotic use has decreased among children and adolescents, but has increased for older adults. Broad-spectrum antibiotic prescribing continues to be on the rise. Public policy initiatives to promote the judicious use of antibiotics should continue and programs targeting older adults should be developed.

Extended-spectrum beta-lactamases (ESBLs) are extremely broad spectrum beta-lactamase enzymes found in a variety of Enterobacteriaceae. Most strains producing these beta-lactamases are Klebsiella pneumoniae, other Klebsiella species (i.e., K. oxytoca), and Escherichia coli. When producing these enzymes, organisms become highly effective at inactivating various beta-lactam antibiotics. In addition, ESBL-producing bacteria are frequently resistant to many classes of antibiotics, resulting in difficult-to-treat infections. Other problems due to ESBL-producing bacteria are difficulty in detecting the presence of ESBLs, limited treatment options, and deleterious impact on clinical outcomes. Clinicians should be familiar with the clinical significance of these enzymes and potential strategies for dealing with this growing problem.

Subsequent to the publication of our article, it was recognized that some details of our PCR and sequencing procedures were not thoroughly described. Page 4016, column 1: Lines 17-30 should read as follows. "Amplicons to be sequenced (high-fidelity PCRs) were prepared using Triple Master Taq polymerase (Eppendorf, Westbury, NY) according to the manufacturer's instructions. The high-fidelity PCRs consisted of a final concentration of 2.5 units of Taq polymerase, 5 l of the template DNA, 200 nM of each primer, 200 M dNTP, 1ϫ buffer with magnesium, and distilled water to achieve a final volume of 50 l. Screening PCRs (nonsequenced) were prepared with Taq polymerase from Invitrogen (Carlsbad, CA) using component concentrations recommended by the manufacturer for the basic PCR protocol. Reactions were run in an MJ mini thermocycler (Bio-Rad Laboratories, Hercules, CA), using a basic cycling program of 94°C for 2 min (first cycle only), 94°C for 15 s, the primer-specific annealing temperature (see references from Table 1) for 30 s, 72°C for 30 s (30 cycles), and 72°C for 3 min. The primers are shown in Table 1 and were synthesized at the Advanced Nucleic Acids Core Facility at the University of Texas Health Science Center at San Antonio. The primers for CTX-M group 3 were redesigned (CTX-M8.WSAgroupIII.F and CTX-M8.WSAgroupIII.R; annealing temperature, 65°C) using sequences from GenBank (accession numbers X92506, AF189721, X92507, and AF252622)." Page 4016, column 2: Lines 4-13 should read as follows. "The predicted PCR product was a 540-bp intragenic fragment of bla OXA-1. PCRs were performed in a DNA thermal cycler (Eppendorf) and prepared as described above using Triple Master Taq polymerase (Eppendorf). Thirty-five cycles were performed for each reaction using the following temperature profile: 94°C for 1 min, 57°C for 1 min, and 72°C for 1 min. All PCR products from the isolates were sequenced. The sequence of the bla OXA-30 gene was deposited under Genbank accession number AF255921.

We report a case of Candida glabrata invasive candidiasis that developed reduced susceptibility to caspofungin during prolonged therapy. Pre-and posttreatment isolates were confirmed to be isogenic, and sequencing of hot spots known to confer echinocandin resistance revealed an F659V substitution within the FKS2 region of the glucan synthase complex.The echinocandins have become first-line therapy in many centers for the treatment of invasive candidiasis due to their proven efficacy, the infrequency of side effects, and the favorable drug interaction profile (12,16,20,23). However, reduced susceptibility to these agents has been reported in patients receiving therapy for invasive candidiasis and is primarily due to mutations within highly conserved regions of FKS1 and FKS2, genes encoding subunits of the glucan synthase enzyme complex (8, 9, 21). We report a case of invasive candidiasis caused by Candida glabrata that developed reduced susceptibility to caspofungin during a prolonged course of therapy with this agent.A 41-year-old previous orthotopic liver recipient, who had no previous antifungal exposure, developed C. glabrata candidemia 8 months after transplantation. Intravenous caspofungin (70-mg load, followed by 50 mg daily) was initiated, and the fungemia cleared within 24 h. Yet cultures of multiple sites remained positive: bronchoalveolar lavage cultures, thought to represent colonization, were positive on days 23 and 52 of therapy; peritoneal fluid and an abdominal wall abscess were positive on day 40; and blood cultures returned positive on day 53. Dialysis dependence, hepatic dysfunction, and drug interaction concerns precluded alternative antifungal agents. The patient died on day 61 of caspofungin therapy after the development of multiorgan failure. Broth microdilution testing performed according to CLSI (formerly NCCLS) standard M27-A2 methodology (17) demonstrated reduced caspofungin susceptibility (MICs of 2 and 8 g/ml at 24 and 48 h, respectively) for C. glabrata isolate 7755 recovered from the peritoneal fluid on day 40 compared to isolate 7754 (MIC of 0.25 g/ml) recovered from the blood prior to antifungal therapy.Random amplification of polymorphic DNA using previously described methods and primers (AP50-1, OPA-18, and OPE-18) (1, 2) strongly suggested strain isogenicity for isolates 7754 and 7755 recovered from this patient. Band patterns were identical for these two isolates with each of the three primers used, while differences in band intensity and location were observed compared to the unrelated isolate 0562 with primers OPA-18 and AP50-1 (Fig.