Showing papers in "Clinical Infectious Diseases in 2004"

Nosocomial Bloodstream Infections in US Hospitals: Analysis of 24,179 Cases from a Prospective Nationwide Surveillance Study

Abstract: Background. Nosocomial bloodstream infections (BSIs) are important causes of morbidity and mortality in the United States. Methods. Data from a nationwide, concurrent surveillance study (Surveillance and Control of Pathogens of Epidemiological Importance [SCOPE]) were used to examine the secular trends in the epidemiology and microbiology of nosocomial BSIs. Results. Our study detected 24,179 cases of nosocomial BSI in 49 US hospitals over a 7-year period from March 1995 through September 2002 (60 cases per 10,000 hospital admissions). Eighty-seven percent of BSIs were monomicrobial. Gram-positive organisms caused 65% of these BSIs, gram-negative organisms caused 25%, and fungi caused 9.5%. The crude mortality rate was 27%. The most-common organisms causing BSIs were coagulasenegative staphylococci (CoNS) (31% of isolates), Staphylococcus aureus (20%), enterococci (9%), and Candida species (9%). The mean interval between admission and infection was 13 days for infection with Escherichia coli, 16 days for S. aureus, 22 days for Candida species and Klebsiella species, 23 days for enterococci, and 26 days for Acinetobacter species. CoNS, Pseudomonas species, Enterobacter species, Serratia species, and Acinetobacter species were more likely to cause infections in patients in intensive care units ( ). In neutropenic patients, infections P ! .001 with Candida species, enterococci, and viridans group streptococci were significantly more common. The proportion of S. aureus isolates with methicillin resistance increased from 22% in 1995 to 57% in 2001 ( , trend P ! .001 analysis). Vancomycin resistance was seen in 2% of Enterococcus faecalis isolates and in 60% of Enterococcus faecium isolates. Conclusion. In this study, one of the largest multicenter studies performed to date, we found that the proportion of nosocomial BSIs due to antibiotic-resistant organisms is increasing in US hospitals.

Practice Guidelines for the Management of Bacterial Meningitis

Abstract: Allan R. Tunkel, Barry J. Hartman, Sheldon L. Kaplan, Bruce A. Kaufman, Karen L. Roos, W. Michael Scheld, and Richard J. Whitley Drexel University College of Medicine, Philadelphia, Pennsylvania; Weill Cornell Medical Center, New York, New York; Baylor College of Medicine, Houston, Texas; Medical College of Wisconsin, Milwaukee; Indiana University School of Medicine, Indianapolis; University of Virginia School of Medicine, Charlottesville; and University of Alabama at Birmingham

Serum Procalcitonin and C-Reactive Protein Levels as Markers of Bacterial Infection: A Systematic Review and Meta-analysis

Abstract: A meta-analysis was performed to evaluate the accuracy of determination of procalcitonin (PCT) and C-reactive protein (CRP) levels for the diagnosis of bacterial infection. The analysis included published studies that evaluated these markers for the diagnosis of bacterial infections in hospitalized patients. PCT level was more sensitive (88% [95% confidence interval [CI], 80%-93%] vs. 75% [95% CI, 62%-84%]) and more specific (81% [95% CI, 67%-90%] vs. 67% [95% CI, 56%-77%]) than CRP level for differentiating bacterial from noninfective causes of inflammation. The Q value for PCT markers was higher (0.82 vs. 0.73). The sensitivity for differentiating bacterial from viral infections was also higher for PCT markers (92% [95% CI, 86%-95%] vs. 86% [95% CI, 65%-95%]); the specificities were comparable (73% [95% CI, 42%-91%] vs. 70% [95% CI, 19%-96%]). The Q value was higher for PCT markers (0.89 vs. 0.83). PCT markers also had a higher positive likelihood ratio and lower negative likelihood ratio than did CRP markers in both groups. On the basis of this analysis, the diagnostic accuracy of PCT markers was higher than that of CRP markers among patients hospitalized for suspected bacterial infections.

Guidelines for Treatment of Candidiasis

Abstract: Peter G. Pappas, John H. Rex, Jack D. Sobel, Scott G. Filler, William E. Dismukes, Thomas J. Walsh, and John E. Edwards Division of Infectious Diseases, University of Alabama at Birmingham, Alabama; AstraZeneca Pharmaceuticals, Manchester, Great Britain; Wayne State University School of Medicine, Detroit, Michigan; Harbor–University of California-Los Angeles Medical Center, Torrance, California; and Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland

Diagnosis and Treatment of Diabetic Foot Infections

Abstract: Benjamin A. Lipsky, Anthony R. Berendt, H. Gunner Deery, John M. Embil, Warren S. Joseph, Adolf W. Karchmer, Jack L. LeFrock, Daniel P. Lew, Jon T. Mader, Carl Norden, and James S. Tan Medical Service, Veterans Affairs Puget Sound Health Care System, and Division of General Internal Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, Washington; Bone Infection Unit, Nuffield Orthopaedic Centre, Oxford, United Kingdom; Northern Michigan Infectious Diseases, Petoskey, Michigan; Section of Infectious Diseases, Department of Medicine, University of Manitoba, Winnipeg, Manitoba; Section of Podiatry, Department of Primary Care, Veterans Affairs Medical Center, Coatesville, Pennsylvania; Division of Infectious Diseases, Department of Medicine, Harvard Medical School, and Beth Israel Deaconess Medical Center, Boston, Massachusetts; Dimensional Dosing Systems, Sarasota, Florida; Department of Medicine, Service of Infectious Diseases, University of Geneva Hospitals, Geneva, Switzerland; Department of Internal Medicine, The Marine Biomedical Institute, and Department of Orthopaedics and Rehabilitation, University of Texas Medical Branch, Galveston, Texas; Department of Medicine, New Jersey School of Medicine and Dentistry, and Cooper Hospital, Camden, New Jersey; and Department of Internal Medicine, Summa Health System, and Northeastern Ohio Universities College of Medicine, Akron, Ohio

Granulomatous Infectious Diseases Associated with Tumor Necrosis Factor Antagonists

Abstract: The relationship between the use of tumor necrosis factor antagonists and onset of granulomatous infection was examined using data collected through the Adverse Event Reporting System of the US Food and Drug Administration for January 1998-September 2002. Granulomatous infections were reported at rates of approximately 239 per 100,000 patients who received infliximab and approximately 74 per 100,000 patients who received etanercept (P<.001). Tuberculosis was the most frequently reported disease, occurring in approximately 144 and approximately 35 per 100,000 infliximab-treated and etanercept-treated patients, respectively (P<.001). Candidiasis, coccidioidomycosis, histoplasmosis, listeriosis, nocardiosis, and infections due to nontuberculous mycobacteria were reported with significantly greater frequency among infliximab-treated patients. Seventy-two percent of these infection occurred < or =90 days after starting infliximab treatment, and 28% occurred after starting etanercept treatment (P<.001). These data indicate a risk of granulomatous infection that was 3.25-fold greater among patients who received infliximab than among those who received etanercept. The clustering of reports shortly after initiation of treatment with infliximab is consistent with reactivation of latent infection.

Clinical Relevance of Bacteriostatic versus Bactericidal Mechanisms of Action in the Treatment of Gram-Positive Bacterial Infections

Abstract: The distinction between bactericidal and bacteriostatic agents appears to be clear according to the in vitro definition, but this only applies under strict laboratory conditions and is inconsistent for a particular agent against all bacteria. The distinction is more arbitrary when agents are categorized in clinical situations. The supposed superiority of bactericidal agents over bacteriostatic agents is of little relevance when treating the vast majority of infections with gram-positive bacteria, particularly in patients with uncomplicated infections and noncompromised immune systems. Bacteriostatic agents (e.g., chloramphenicol, clindamycin, and linezolid) have been effectively used for treatment of endocarditis, meningitis, and osteomyelitis--indications that are often considered to require bactericidal activity. Although bacteriostatic/bactericidal data may provide valuable information on the potential action of antibacterial agents in vitro, it is necessary to combine this information with pharmacokinetic and pharmacodynamic data to provide more meaningful prediction of efficacy in vivo. The ultimate guide to treatment of any infection must be clinical outcome.

Trends in Antimicrobial Drug Development: Implications for the Future

Abstract: The need for new antimicrobial agents is greater than ever because of the emergence of multidrug resistance in common pathogens, the rapid emergence of new infections, and the potential for use of multidrug-resistant agents in bioweapons. Paradoxically, some pharmaceutical companies have indicated that they are curtailing anti-infective research programs. We evaluated the United States Food and Drug Administration (FDA) databases of approved drugs and the research and development programs of the world's largest pharmaceutical and biotechnology companies to document trends in the development of new antimicrobial agents. FDA approval of new antibacterial agents decreased by 56% over the past 20 years (1998-2002 vs. 1983-1987). Projecting future development, new antibacterial agents constitute 6 of 506 drugs disclosed in the developmental programs of the largest pharmaceutical and biotechnology companies. Despite the critical need for new antimicrobial agents, the development of these agents is declining. Solutions encouraging and facilitating the development of new antimicrobial agents are needed.

Antimicrobial Prophylaxis for Surgery: An Advisory Statement from the National Surgical Infection Prevention Project

Abstract: In January 2003, leadership of the Medicare National Surgical Infection Prevention Project hosted the Surgical Infection Prevention Guideline Writers Workgroup (SIPGWW) meeting. The objectives were to review areas of agreement among the most-recently published guidelines for surgical antimicrobial prophylaxis, to address inconsistencies, and to discuss issues not currently addressed. The participants included authors from most of the groups that have published North American guidelines for antimicrobial prophylaxis, as well as authors from several specialty colleges. Nominal group process was used to draft a consensus paper that was widely circulated for comment. The consensus positions of SIPGWW include that infusion of the first antimicrobial dose should begin within 60 min before surgical incision and that prophylactic antimicrobials should be discontinued within 24 h after the end of surgery. This advisory statement provides an overview of other issues related to antimicrobial prophylaxis, including specific suggestions regarding antimicrobial selection.

FoodNet Estimate of the Burden of Illness Caused by Nontyphoidal Salmonella Infections in the United States

Abstract: To determine the burden of Salmonella infections in the United States, Foodborne Diseases Active Surveillance Network (FoodNet) investigators conducted population-based active surveillance for culture-confirmed Salmonella infections during 1996‐1999 at FoodNet laboratories. In addition, all clinical microbiology FoodNet laboratories were surveyed to determine their practices for isolating Salmonella. Telephone interviews were also conducted among residents of the FoodNet sites to determine the proportion of persons with diarrheal illness who sought medical care and the proportion who submitted stool specimens for bacterial culture. Using our model, we estimated that there were 1.4 million nontyphoidal Salmonella infections in the United States, resulting in 168,000 physician office visits per year during 1996‐1999. Including both culture-confirmed infections and those not confirmed by culture, we estimated that Salmonella infections resulted in 15,000 hospitalizations and 400 deaths annually. These estimates indicate that salmonellosis presents a major ongoing burden to public health.

Micafungin versus Fluconazole for Prophylaxis against Invasive Fungal Infections during Neutropenia in Patients Undergoing Hematopoietic Stem Cell Transplantation

Abstract: 5 for the National Institute of Allergy and Infectious Diseases Mycoses Study Group a We hypothesized that chemoprophylaxis with the echinocandin micafungin would be an effective agent for antifungal prophylaxis during neutropenia in patients undergoing hematopoietic stem cell transplantation (HSCT). We therefore conducted a randomized, double-blind, multi-institutional, comparative phase III trial, involving 882 adult and pediatric patients, of 50 mg of micafungin (1 mg/kg for patients weighing !50 kg) and 400 mg of fluconazole (8 mg/kg for patients weighing !50 kg) administered once per day. Success was defined as the absence of suspected, proven, or probable invasive fungal infection (IFI) through the end of therapy and as the absence of proven or probable IFI through the end of the 4-week period after treatment. The overall efficacy of micafungin was superior to that of fluconazole as antifungal prophylaxis during the neutropenic phase after HSCT (80.0% in the micafungin arm vs. 73.5% in the fluconazole arm (difference, 6.5%); 95% confidence interval, 0.9%-12%; ). This randomized trial demonstrates the efficacy of an P p .03

The Safety and Efficacy of Daptomycin for the Treatment of Complicated Skin and Skin-Structure Infections

Abstract: Daptomycin is the first available agent from a new class of antibiotics, the cyclic lipopeptides, that has activity against a broad range of gram-positive pathogens, including organisms that are resistant to methicillin, vancomycin, and other currently available agents. Daptomycin (4 mg/kg intravenously [iv] every 24 h for 7-14 days) was compared with conventional antibiotics (penicillinase-resistant penicillins [4-12 g iv per day] or vancomycin [1 g iv every 12 h]) in 2 randomized, international trials involving 1092 patients with complicated skin and skin-structure infections. Among 902 clinically evaluable patients, clinical success rates were 83.4% and 84.2% for the daptomycin- and comparator-treated groups, respectively (95% confidence interval, -4.0 to 5.6). Among patients successfully treated with iv daptomycin, 63% required only 4-7 days of therapy, compared with 33% of comparator-treated patients (P<.0001). The frequency and distribution of adverse events were similar among both treatment groups. Overall, the safety and efficacy of daptomycin were comparable with conventional therapy.

Contamination, Disinfection, and Cross-Colonization: Are Hospital Surfaces Reservoirs for Nosocomial Infection?

Abstract: Despite documentation that the inanimate hospital environment (e.g., surfaces and medical equipment) becomes contaminated with nosocomial pathogens, the data that suggest that contaminated fomites lead to nosocomial infections do so indirectly. Pathogens for which there is more-compelling evidence of survival in environmental reservoirs include Clostridium difficile, vancomycin-resistant enterococci, and methicillin-resistant Staphylococcus aureus, and pathogens for which there is evidence of probable survival in environmental reservoirs include norovirus, influenza virus, severe acute respiratory syndrome-associated coronavirus, and Candida species. Strategies to reduce the rates of nosocomial infection with these pathogens should conform to established guidelines, with an emphasis on thorough environmental cleaning and use of Environmental Protection Agency-approved detergent-disinfectants.

Efficacy and Safety of Caspofungin for Treatment of Invasive Aspergillosis in Patients Refractory to or Intolerant of Conventional Antifungal Therapy

Abstract: Background Invasive aspergillosis (IA) is an important cause of morbidity and mortality among immunocompromised patients. Echinocandins are novel antifungal molecules with in vitro and in vivo activity against Aspergillus species. Methods We investigated the efficacy and safety of caspofungin in the treatment of IA. Ninety patients with IA who were refractory to or intolerant of amphotericin B, lipid formulations of amphotericin B, or triazoles were enrolled to receive caspofungin. Results Efficacy was assessed for 83 patients who had infection consistent with definitions of IA and who received >or=1 dose of study drug. Common underlying conditions included hematologic malignancy (48% of patients), allogeneic blood and marrow transplantation (25% of patients), and solid-organ transplantation (11% of patients). Seventy-one patients (86%) were refractory to and 12 patients (14%) were intolerant of previous therapy. A favorable response to caspofungin therapy was observed in 37 (45%) of 83 patients, including 32 (50%) of 64 with pulmonary aspergillosis and 3 (23%) of 13 with disseminated aspergillosis. Two patients discontinued caspofungin therapy because of drug-related adverse events. Drug-related nephrotoxicity and hepatotoxicity occurred infrequently. Conclusion Caspofungin demonstrated usefulness in the salvage treatment of IA.

Combination Antifungal Therapy for Invasive Aspergillosis

Abstract: Background. Aspergillosis therapy with amphotericin, azoles, or echinocandins is associated with substantial mortality, ranging from 30% to 80%, depending on the stage of infection and the host's underlying disease. The results of in vitro studies and animal models suggest that combination therapy with azoles and echinocandins may have additive activity against Aspergillus species. Methods. We evaluated the outcomes of patients with aspergillosis who experienced failure of initial therapy with amphotericin B formulations and received either voriconazole (n = 31) or a combination of voriconazole and caspofungin (n = 16) for salvage therapy. Results. The combination of voriconazole and caspofungin was associated with improved 3-month survival rate, compared with voriconazole alone (hazard ratio [HR], 0.42; 95% confidence interval [Cl], 0.17-1.1; P = .048). In multivariable models, salvage therapy with the combination of voriconazole and caspofungin was associated with reduced mortality, compared with therapy with voriconazole (HR, 0.28; 95% Cl, 0.28-0.92; P = .011), independent of other prognostic variables (e.g., receipt of transplant and type of conditioning therapy). The probability of death due to aspergillosis was lowest in patients who received the combination regimen. Conclusions. Randomized trials are warranted to determine whether this combination should be used as primary therapy for aspergillosis.

Risk Factors for Sporadic Campylobacter Infection in the United States: A Case-Control Study in FoodNet Sites

Abstract: Campylobacter is a common cause of gastroenteritis in the United States. We conducted a population-based case-control study to determine risk factors for sporadic Campylobacter infection. During a 12-month study, we enrolled 1316 patients with culture-confirmed Campylobacter infections from 7 states, collecting demographic, clinical, and exposure data using a standardized questionnaire. We interviewed 1 matched control subject for each case patient. Thirteen percent of patients had traveled abroad. In multivariate analysis of persons who had not traveled, the largest population attributable fraction (PAF) of 24% was related to consumption of chicken prepared at a restaurant. The PAF for consumption of nonpoultry meat that was prepared at a restaurant was also large (21%); smaller proportions of illness were associated with other food and nonfood exposures. Efforts to reduce contamination of poultry with Campylobacter should benefit public health. Restaurants should improve food-handling practices, ensure adequate cooking of meat and poultry, and consider purchasing poultry that has been treated to reduce Campylobacter contamination.

β-D-glucan as a diagnostic adjunct for invasive fungal infections: Validation, cutoff development, and performance in patients with acute myelogenous leukemia and myelodysplastic syndrome

Abstract: The Glucatell (1-->3)- beta-D-glucan (BG) detection assay (Associates of Cape Cod) was studied as a diagnostic adjunct for invasive fungal infections (IFIs). On the basis of findings from a preliminary study of 30 candidemic subjects and 30 healthy adults, a serum BG level of >or=60 pg/mL was chosen as the cutoff. Testing was performed with serial serum samples obtained from 283 subjects with acute myeloid leukemia or myelodysplastic syndrome who were receiving antifungal prophylaxis. At least 1 serum sample was positive for BG at a median of 10 days before the clinical diagnosis in 100% of subjects with a proven or probable IFI. IFIs included candidiasis, fusariosis, trichosporonosis, and aspergillosis. Absence of a positive BG finding had a 100% negative predictive value, and the specificity of the test was 90% for a single positive test result and >or=96% for >or=2 sequential positive results. The Glucatell serum BG detection assay is highly sensitive and specific as a diagnostic adjunct for IFI.

Methicillin-Resistant Staphylococcus aureus (MRSA) Nares Colonization at Hospital Admission and Its Effect on Subsequent MRSA Infection

Abstract: Background. Asymptomatic colonization with methicillin-resistant Staphylococcus aureus (MRSA) has been described as a risk factor for subsequent MRSA infection. MRSA is an important nosocomial pathogen but has currently been reported in patients without typical risk factors for nosocomial acquisition. This study was designed to evaluate the impact of asymptomatic nares MRSA colonization on the development of subsequent MRSA infection. The incidence of MRSA infection was examined in patients with and patients without MRSA or methicillin-susceptible S. aureus (MSSA) colonization at admission to the hospital and in those who developed colonization during hospitalization. Methods. Patients admitted to 5 representative hospital units were prospectively evaluated. Nares samples were obtained for culture at admission and during hospitalization. Laboratory culture results were monitored to identify all MRSA infections that occurred during the study period and 1 year thereafter. Results. Of the 758 patients who had cultures of nares samples performed at admission, 3.4% were colonized with MRSA, and 21% were colonized with MSSA. A total of 19% of patients with MRSA colonization at admission and 25% who acquired MRSA colonization during hospitalization developed infection with MRSA, compared with 1.5% and 2.0% of patients colonized with MSSA ( ) and uncolonized ( ), respectively, at admission. P ! .01 P ! .01 MRSA colonization at admission increased the risk of subsequent MRSA infection, compared with MSSA colonization (relative risk [RR], 13; 95% confidence interval [CI], 2.7‐64) or no staphylococcal colonization (RR, 9.5; 95% CI, 3.6‐25) at admission. Acquisition of MRSA colonization also increased the risk for subsequent MRSA infection, compared with no acquisition (RR, 12; 95% CI, 4.0‐38). Conclusion. MRSA colonization of nares, either present at admission to the hospital or acquired during hospitalization, increases the risk for MRSA infection. Identifying MRSA colonization at admission could target a high-risk population that may benefit from interventions to decrease the risk for subsequent MRSA infection.

Primary Care Guidelines for the Management of Persons Infected with Human Immunodeficiency Virus: 2009 Update by the HIV Medicine Association of the Infectious Diseases Society of America

Abstract: Evidence-based guidelines for the management of persons infected with human immunodeficiency virus (HIV) were prepared by an expert panel of the HIV Medicine Association of the Infectious Diseases Society of America. These updated guidelines replace those published in 2004. The guidelines are intended for use by health care providers who care for HIV-infected patients or patients who may be at risk for acquiring HIV infection. Since 2004, new antiretroviral drugs and classes have become available, and the prognosis of persons with HIV infection continues to improve. However, with fewer complications and increased survival, HIVinfected persons are increasingly developing common health problems that also affect the general population. Some of these conditions may be related to HIV infection itself and its treatment. HIV-infected persons should be managed and monitored for all relevant age- and gender-specific health problems. New information based on publications from the period 2003‐2008 has been incorporated into this document.

Antibiotic Therapy for Klebsiella pneumoniae Bacteremia: Implications of Production of Extended-Spectrum β-Lactamases

Abstract: The prevalence of extended-spectrum b-lactamase (ESBL) production by Klebsiella pneumonia approaches 50% in some countries, with particularly high rates in eastern Europe and Latin America. No randomized trials have ever been performed on treatment of bacteremia due to ESBL-producing organisms; existing data comes only from retrospective, single-institution studies. In a prospective study of 455 consecutive episodes of Klebsiella pneumoniae bacteremia in 12 hospitals in 7 countries, 85 episodes were due to an ESBL–producing organism. Failure to use an antibiotic active against ESBL-producing K. pneumoniae was associated with extremely high mortality. Use of a carbapenem (primarily imipenem) was associated with a significantly lower 14-day mortality than was use of other antibiotics active in vitro. Multivariate analysis including other predictors of mortality showed that use of a carbapenem during the 5-day period after onset of bacteremia due to an ESBL-producing organism was independently associated with lower mortality. Antibiotic choice is particularly important in seriously ill patients with infections due to ESBL-producing K. pneumoniae.

Pyogenic Liver Abscess: Recent Trends in Etiology and Mortality

Abstract: Background Pyogenic liver abscess, a potentially life-threatening disease, has undergone significant changes in epidemiology, management, and mortality over the past several decades. Methods We reviewed the data for patients admitted to Bellevue Hospital and New York University Downtown Hospital (New York, New York) over a 10-year period. Results Of 79 cases reviewed, 43% occurred in patients with underlying biliary disease. The most common symptoms were fever, chills, and right upper quadrant pain or tenderness. The most common laboratory abnormalities were an elevated white blood cell count (in 68% of cases), temperature >or=38.1 degrees C (90%), a low albumin level (70.2%), and an elevated alkaline phosphatase level (67%). Seventy percent of the abscesses were in the right lobe, and 77% were solitary. Klebsiella pneumoniae was identified in 41% of cases in which a pathogen was recovered. Eighteen (50%) of 36 Asian patients had K. pneumoniae isolated, in contrast to 6 (27.3%) of 22 non-Asian patients (not statistically significant). Fifty-six percent of cases involved treatment with percutaneous drainage. Although prior reports noted mortality of 11%-31%, we observed only 2 deaths (mortality, 2.5%). Conclusions The data suggest that K. pneumoniae has become the predominant etiology of pyogenic liver abscess and that mortality from this disease has decreased substantially.

Treatment Outcomes for Serious Infections Caused by Methicillin-Resistant Staphylococcus aureus with Reduced Vancomycin Susceptibility

Abstract: Although infections caused by methicillin-resistant Staphylococcus aureus with reduced vancomycin susceptibility (SA-RVS) have been reported from a number of countries, including Australia, the optimal therapy is unknown. We reviewed the clinical features, therapy, and outcome of 25 patients with serious infections due to SA-RVS in Australia and New Zealand. Eight patients had endocarditis, 9 had bacteremia associated with deep-seated infection, 6 had osteomyelitis or septic arthritis, and 2 had empyema. All patients had received vancomycin before the isolation of SA-RVS, and glycopeptide treatment had failed for 19 patients (76%). Twenty-one patients subsequently received active treatment, which was effective for 16 patients (76%). Eighteen patients received linezolid, which was effective in 14 (78%), including 4 patients with endocarditis. Twelve patients received a combination of rifampicin and fusidic acid. Surgical intervention was required for 15 patients (60%). Antibiotic therapy, especially linezolid with or without rifampicin and fusidic acid, in conjunction with surgical debulking is effective therapy for the majority of patients with serious infections (including endocarditis) caused by SA-RVS.

Practice Guidelines for Outpatient Parenteral Antimicrobial Therapy

Abstract: These guidelines were formulated to assist physicians and other health care professionals with various aspects of the administration of outpatient parenteral antimicrobial therapy (OPAT). Although there are many reassuring retrospective studies on the efficacy and safety of OPAT, few prospective studies have been conducted to compare the risks and outcomes for patients who receive treatment as outpatients rather than as inpatients. Because truly evidence-based studies are lacking, the present guidelines are formulated from the collective experience of the committee members and advisors from related organizations.

Laboratory Diagnosis of Urinary Tract Infections in Adult Patients

Abstract: Urinary tract infections (UTIs) are among the most common bacterial infections and account for a significant part of the workload in clinical microbiology laboratories. Enteric bacteria (in particular, Escherichia coli) remain the most frequent cause of UTIs, although the distribution of pathogens that cause UTIs is changing. More important is the increase in resistance to some antimicrobial agents, particularly the resistance to trimethoprim-sulfamethoxazole seen in E. coli. Physicians distinguish UTIs from other diseases that have similar clinical presentations with use of a small number of tests, none of which, if used individually, have adequate sensitivity and specificity. Among the diagnostic tests, urinalysis is useful mainly for excluding bacteriuria. Urine culture may not be necessary as part of the evaluation of outpatients with uncomplicated UTIs, but it is necessary for outpatients who have recurrent UTIs, experience treatment failures, or have complicated UTIs, as well as for inpatients who develop UTIs.

Emergence of Carbapenem-Resistant Klebsiella Species Possessing the Class A Carbapenem-Hydrolyzing KPC-2 and Inhibitor-Resistant TEM-30 β-Lactamases in New York City

Abstract: Nineteen isolates of carbapenem-resistant Klebsiella species were recovered from 7 hospitals in New York City. Most K. pneumoniae belonged to a single ribotype. Nucleotide sequencing identified KPC-2, a carbapenem-hydrolyzing beta -lactamase. In 3 strains, TEM-30, an inhibitor-resistant beta -lactamase, was detected. Carbapenem-resistant Klebsiella species possessing KPC-2 are endemic in New York City. This study documents the identification of an inhibitor-resistant TEM beta -lactamase in the United States.

Rickettsia parkeri: A newly recognized cause of spotted fever rickettsiosis in the United States

Abstract: Ticks, including many that bite humans, are hosts to several obligate intracellular bacteria in the spotted fever group (SFG) of the genus Rickettsia. Only Rickettsia rickettsii, the agent of Rocky Mountain spotted fever, has been definitively associated with disease in humans in the United States. Herein we describe disease in a human caused by Rickettsia parkeri, an SFG rickettsia first identified >60 years ago in Gulf Coast ticks (Amblyomma maculatum) collected from the southern United States. Confirmation of the infection was accomplished using serological testing, immunohistochemical staining, cell culture isolation, and molecular methods. Application of specific laboratory assays to clinical specimens obtained from patients with febrile, eschar-associated illnesses following a tick bite may identify additional cases of R. parkeri rickettsiosis and possibly other novel SFG rickettsioses in the United States.

Natural History of Community-Acquired Methicillin-Resistant Staphylococcus aureus Colonization and Infection in Soldiers

Abstract: Background. Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging pathogen for which the prevalence, risk factors, and natural history are incompletely understood. Methods. In this prospective observational study, we evaluated 812 US Army soldiers to determine the prevalence of and risk factors for CA-MRSA colonization and the changes in colonization rate over time, as well as to determine the clinical significance of CA-MRSA colonization. Demographic data and swab samples from the nares for S. aureus cultures were obtained from participants at the start of their training and 8-10 weeks later. Over this time period, participants were observed prospectively to monitor for soft-tissue infections. S. aureus isolates were characterized by in vitro examination of antibiotic susceptibilities, mecA confirmation, pulsed-field gel electrophoresis, and Panton-Valentine leukocidin (PVL) gene testing. Results. At the initial sampling, 24 of the participants (3%) were colonized with CA-MRSA, 9 of whom (38%) developed soft-tissue infections during the study period. In contrast, 229 participants (28%) were colonized with methicillin-susceptible S. aureus (MSSA), 8 (3%) of whom developed clinical infections during the same period (relative risk, 10.7; 95% confidence interval, 4.6-25.2; P<.001). At follow-up culture, the CA-MRSA colonization rate dropped to 1.6% without eradication efforts. Previous antibiotic use was a risk factor for CA-MRSA colonization at the initial sampling (P =.03). PVL genes were detected in 66% of 45 recovered CA-MRSA isolates, including all 9 clinical isolates available for analysis. Of subjects hospitalized, 5 of 6 had PVL-positive CA-MRSA infections. Conclusions. CA-MRSA colonization with PVL-positive strains was associated with a significant risk of soft-tissue infection, suggesting that CA-MRSA may be more virulent than MSSA. Previous antibiotic use may play a role in CA-MRSA colonization.

“Collateral Damage” from Cephalosporin or Quinolone Antibiotic Therapy

Abstract: “Collateral damage” is a term used to refer to ecological adverse effects of antibiotic therapy; namely, the selection of drug-resistant organisms and the unwanted development of colonization or infection with multidrug-resistant organisms. The risk of such damage can be assessed for different antibiotic classes by a variety of epidemiologic studies. Cephalosporin use has been linked to subsequent infection with vancomycin-resistant enterococci, extended-spectrum b-lactamase–producing Klebsiella pneumoniae, b-lactam–resistant Acinetobacter species, and Clostridium difficile. Quinolone use has been linked to infection with methicillin-resistant Staphylococcus aureus and with increasing quinolone resistance in gram-negative bacilli, such as Pseudomonas aeruginosa. Neither third-generation cephalosporins nor quinolones appear suitable for sustained use in hospitals as “workhorse” antibiotic therapy. Traditionally, studies of antimicrobial therapy have assessed clinical and bacteriological efficacy in the treatment of infection. This is intuitive and is clearly the most appropriate way to study the effectiveness of antibiotics. However, treatment of serious communityacquired and hospital-acquired infections with antibiotics that may be associated with “collateral damage”— that is, the selection of antibiotic-resistant organisms or Clostridium difficile and the unwanted development of colonization or infection with such organisms—also needs to be evaluated. Although such collateral damage has pertinence to the outpatient treatment of community-acquired pneumonia (CAP), here I concentrate on the effects of inpatient treatment with antibiotics commonly used for pneumonia and on the 2 antibiotic classes most commonly linked to collateral damage— cephalosporins and quinolones.

Laboratory diagnosis of urinary tract infections in adult patients. Authors' reply

Abstract: Urinary tract infections (UTIs) are among the most common bacterial infections and account for a significant part of the workload in clinical microbiology laboratories. Enteric bacteria (in particular, Escherichia coli) remain the most frequent cause of UTIs, although the distribution of pathogens that cause UTIs is changing. More important is the increase in resistance to some antimicrobial agents, particularly the resistance to trimethoprim-sulfamethoxazole seen in E. coli. Physicians distinguish UTIs from other diseases that have similar clinical presentations with use of a small number of tests, none of which, if used individually, have adequate sensitivity and specificity. Among the diagnostic tests, urinalysis is useful mainly for excluding bacteriuria. Urine culture may not be necessary as part of the evaluation of outpatients with uncomplicated UTIs, but it is necessary for outpatients who have recurrent UTIs, experience treatment failures, or have complicated UTIs, as well as for inpatients who develop UTIs.

Epidemiology of Candidemia in Swiss Tertiary Care Hospitals: Secular Trends, 1991–2000

Abstract: Candida species are among the most common bloodstream pathogens in the United States, where the emergence of azole-resistant Candida glabrata and Candida krusei are major concerns. Recent comprehensive longitudinal data from Europe are lacking. We conducted a nationwide survey of candidemia during 1991-2000 in 17 university and university-affiliated hospitals representing 79% of all tertiary care hospital beds in Switzerland. The number of transplantations and bloodstream infections increased significantly (P<.001). A total of 1137 episodes of candidemia were observed: Candida species ranked seventh among etiologic agents (2.9% of all bloodstream isolates). The incidence of candidemia was stable over a 10-year period. C. albicans remained the predominant Candida species recovered (66%), followed by C. glabrata (15%). Candida tropicalis emerged (9%), the incidence of Candida parapsilosis decreased (1%), and recovery of C. krusei remained rare (2%). Fluconazole consumption increased significantly (P<.001). Despite increasing high-risk activities, the incidence of candidemia remained unchanged, and no shift to resistant species occurred.