Showing papers in "Clinical Infectious Diseases in 2012"

2012 Infectious Diseases Society of America Clinical Practice Guideline for the Diagnosis and Treatment of Diabetic Foot Infections

Abstract: Foot infections are a common and serious problem in persons with diabetes Diabetic foot infections (DFIs) typically begin in a wound, most often a neuropathic ulceration While all wounds are colonized with microorganisms, the presence of infection is defined by ≥2 classic findings of inflammation or purulence Infections are then classified into mild (superficial and limited in size and depth), moderate (deeper or more extensive), or severe (accompanied by systemic signs or metabolic perturbations) This classification system, along with a vascular assessment, helps determine which patients should be hospitalized, which may require special imaging procedures or surgical interventions, and which will require amputation Most DFIs are polymicrobial, with aerobic gram-positive cocci (GPC), and especially staphylococci, the most common causative organisms Aerobic gram-negative bacilli are frequently copathogens in infections that are chronic or follow antibiotic treatment, and obligate anaerobes may be copathogens in ischemic or necrotic wounds Wounds without evidence of soft tissue or bone infection do not require antibiotic therapy For infected wounds, obtain a post-debridement specimen (preferably of tissue) for aerobic and anaerobic culture Empiric antibiotic therapy can be narrowly targeted at GPC in many acutely infected patients, but those at risk for infection with antibiotic-resistant organisms or with chronic, previously treated, or severe infections usually require broader spectrum regimens Imaging is helpful in most DFIs; plain radiographs may be sufficient, but magnetic resonance imaging is far more sensitive and specific Osteomyelitis occurs in many diabetic patients with a foot wound and can be difficult to diagnose (optimally defined by bone culture and histology) and treat (often requiring surgical debridement or resection, and/or prolonged antibiotic therapy) Most DFIs require some surgical intervention, ranging from minor (debridement) to major (resection, amputation) Wounds must also be properly dressed and off-loaded of pressure, and patients need regular follow-up An ischemic foot may require revascularization, and some nonresponding patients may benefit from selected adjunctive measures Employing multidisciplinary foot teams improves outcomes Clinicians and healthcare organizations should attempt to monitor, and thereby improve, their outcomes and processes in caring for DFIs

Epidemiology and Clinical Manifestations of Mucormycosis

Abstract: Mucormycosis is an emerging angioinvasive infection caused by the ubiquitous filamentous fungi of the Mucorales order of the class of Zygomycetes. Mucormycosis has emerged as the third most common invasive mycosis in order of importance after candidiasis and aspergillosis in patients with hematological and allogeneic stem cell transplantation. Mucormycosis also remains a threat in patients with diabetes mellitus in the Western world. Furthermore, this disease is increasingly recognized in recently developed countries, such as India, mainly in patients with uncontrolled diabetes or trauma. Epidemiological data on this type of mycosis are scant. Therefore, our ability to determine the burden of disease is limited. Based on anatomic localization, mucormycosis can be classified as one of 6 forms: (1) rhinocerebral, (2) pulmonary, (3) cutaneous, (4) gastrointestinal, (5) disseminated, and (6) uncommon presentations. The underlying conditions can influence clinical presentation and outcome. This review describes the emerging epidemiology and the clinical manifestations of mucormycosis.

Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae: importance of combination therapy

Abstract: Background The spread of Klebsiella pneumoniae (Kp) strains that produce K. pneumoniae carbapenemases (KPCs) has become a significant problem, and treatment of infections caused by these pathogens is a major challenge for clinicians. Methods In this multicenter retrospective cohort study, conducted in 3 large Italian teaching hospitals, we examined 125 patients with bloodstream infections (BSIs) caused by KPC-producing Kp isolates (KPC-Kp) diagnosed between 1 January 2010 and 30 June 2011. The outcome measured was death within 30 days of the first positive blood culture. Survivor and nonsurvivor subgroups were compared to identify predictors of mortality. Results The overall 30-day mortality rate was 41.6%. A significantly higher rate was observed among patients treated with monotherapy (54.3% vs 34.1% in those who received combined drug therapy; P = .02). In logistic regression analysis, 30-day mortality was independently associated with septic shock at BSI onset (odds ratio [OR]: 7.17; 95% confidence interval [CI]: 1.65-31.03; P = .008); inadequate initial antimicrobial therapy (OR: 4.17; 95% CI: 1.61-10.76; P = .003); and high APACHE III scores (OR: 1.04; 95% CI: 1.02-1.07; P Conclusions KPC-Kp BSIs are associated with high mortality. To improve survival, combined treatment with 2 or more drugs with in vitro activity against the isolate, especially those also including a carbapenem, may be more effective than active monotherapy.

Clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America.

Abstract: The guideline is intended for use by healthcare providers who care for adult and pediatric patients with group A streptococcal pharyngitis. The guideline updates the 2002 Infectious Diseases Society of America guideline and discusses diagnosis and management, and recommendations are provided regarding antibiotic choices and dosing. Penicillin or amoxicillin remain the treatments of choice, and recommendations are made for the penicillin-allergic patient, which now include clindamycin.

Intestinal Domination and the Risk of Bacteremia in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Abstract: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for a range of malignant and nonmalignant disorders. Pre-transplant conditioning transiently ablates circulating granulocytes and monocytes and markedly increases susceptibility to disseminated infections [1, 2]. Mucosal barrier injury is also a complication of allo-HSCT and enables commensal microbes to invade underlying tissues and the bloodstream [3]. As a result, systemic bacterial infections are frequent during the early transplant period [4–6]. Vancomycin-resistant Enterococcus (VRE), viridians-group Streptococcus, and aerobic gram-negative bacteria are the most common causes of bloodstream infection following allo-HSCT [5–8]. Why some patients develop bacteremia while others do not is unclear. The complex microbial populations colonizing the human intestine provide resistance to infection. The intestinal microbiota also serves as a sanctuary for highly antibiotic-resistant bacteria [9]. Prior studies using in vitro culture methods have characterized microbial populations inhabiting the intestine [10]; more recently, massively parallel pyrosequencing of bacterial 16S ribosomal RNA (rRNA) encoding genes has provided new insights into the composition and complexity of the intestinal microbiota by identifying bacterial taxons that are not readily cultivated in vitro [11–14]. These approaches have demonstrated the compositional changes and resilience of the intestinal microbiota of healthy individuals after antibiotic treatment [12]. Studies with mice demonstrated dramatic changes in the microbiota of the ileum and cecum following antibiotic treatment, and dramatic expansion of antibiotic-resistant microbes such as vancomycin-resistant Enterococcus (VRE) [15]. Intestinal expansion of VRE following antibiotic treatment is also seen in humans, with episodes of VRE domination in patients undergoing allo-HSCT preceding the development of VRE bacteremia in 2 patients [15]. Because the effect of allo-HSCT conditioning, prolonged neutropenia, and antibiotic administration on the gastrointestinal tract microbiota is unknown, we characterized the fecal microbiota of patients undergoing transplant at multiple time points using 454 pyrosequencing of 16S rRNA genes. (Data deposition: 454 pyrosequencing reads have been deposited in the National Center for Biotechnology Information Sequence Read Archive.)

Impact of treatment strategy on outcomes in patients with candidemia and other forms of invasive candidiasis: a patient-level quantitative review of randomized trials

Abstract: Background. Invasive candidiasis (IC) is an important healthcare-related infection, with increasing incidence and a crude mortality exceeding 50%. Numerous treatment options are available yet comparative studies have not identified optimal therapy. Methods. We conducted an individual patient-level quantitative review of randomized trials for treatment of IC and to assess the impact of host-, organism-, and treatment-related factors on mortality and clinical cure. Studies were identified by searching computerized databases and queries of experts in the field for randomized trials comparing the effect of $2 antifungals for treatment of IC. Univariate and multivariable analyses were performed to determine factors associated with patient outcomes. Results. Data from 1915 patients were obtained from 7 trials. Overall mortality among patients in the entire data set was 31.4%, and the rate of treatment success was 67.4%. Logistic regression analysis for the aggregate data set identified increasing age (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.00‐1.02; P 5 .02), the Acute Physiology and Chronic Health Evaluation II score (OR, 1.11; 95% CI, 1.08‐1.14; P 5 .0001), use of immunosuppressive therapy (OR, 1.69; 95% CI, 1.18‐2.44; P 5 .001), and infection with Candida tropicalis (OR, 1.64; 95% CI, 1.11‐2.39; P 5 .01) as predictors of mortality. Conversely, removal of a central venous catheter (CVC) (OR, 0.50; 95% CI, .35‐.72; P 5 .0001) and treatment with an echinocandin antifungal (OR, 0.65; 95% CI, .45‐.94; P 5 .02) were associated with decreased mortality. Similar findings were observed for the clinical success end point. Conclusions. Two treatment-related factors were associated with improved survival and greater clinical success: use of an echinocandin and removal of the CVC.

The Frequency of Autoimmune N-Methyl-D-Aspartate Receptor Encephalitis Surpasses That of Individual Viral Etiologies in Young Individuals Enrolled in the California Encephalitis Project

Abstract: Background. In 2007, the California Encephalitis Project (CEP), which was established to study the epidemiology of encephalitis, began identifying cases of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. Increasing numbers of anti-NMDAR encephalitis cases have been identified at the CEP, and this form rivals commonly known viral etiologies as a causal agent. We report here the relative frequency and differences among encephalitides caused by anti-NMDAR and viral etiologies within the CEP experience. Methods. Demographic, frequency, and clinical data from patients with anti-NMDAR encephalitis are compared with those with viral encephalitic agents: enterovirus, herpes simplex virus type 1 (HSV-1), varicella-zoster virus (VZV), and West Nile virus (WNV). All examined cases presented to the CEP between September 2007 and February 2011 and are limited to individuals aged #30 years because of the predominance of anti-NMDAR encephalitis in this group. The diagnostic costs incurred in a single case are also included. Results. Anti-NMDAR encephalitis was identified .4 times as frequently as HSV-1, WNV, or VZV and was the leading entity identified in our cohort. We found that 65% of anti-NMDAR encephalitis occurred in patients aged #18 years. This disorder demonstrated a predilection, which was not observed with viral etiologies, for females (P, .01). Seizures, language dysfunction, psychosis, and electroencephalographic abnormalities were significantly more frequent in patients with anti-NMDAR encephalitis (P , .05), and autonomic instability occurred exclusively in this group. Discussion. Anti-NMDAR encephalitis rivals viral etiologies as a cause of encephalitis within the CEP cohort. This entity deserves a prominent place on the encephalitic differential diagnosis to avoid unnecessary diagnostic and treatment costs, and to permit a more timely treatment.

Preeminence of Staphylococcus aureus in Infective Endocarditis: A 1-Year Population-Based Survey

Abstract: Background. Observational studies showed that the profile of infective endocarditis (IE) significantly changed over the past decades. However, most studies involved referral centers. We conducted a population-based study to control for this referral bias. The objective was to update the description of characteristics of IE in France and to compare the profile of community-acquired versus healthcare-associated IE. Methods. A prospective population-based observational study conducted in all medical facilities from 7 French regions (32% of French individuals aged $18 years) identified 497 adults with Duke-Li‐definite IE who were first admitted to the hospital in 2008. Main measures included age-standardized and sex-standardized incidence of IE and multivariate Cox regression analysis for risk factors of in-hospital death. Results. The age-standardized and sex-standardized annual incidence of IE was 33.8 (95% confidence interval [CI], 30.8‐36.9) cases per million inhabitants. The incidence was highest in men aged 75‐79 years. A majority of patients had no previously known heart disease. Staphylococci were the most common causal agents, accounting for 36.2% of cases (Staphylococcus aureus, 26.6%; coagulase-negative staphylococci, 9.7%). Healthcare-associated IE represented 26.7% of all cases and exhibited a clinical pattern significantly different from that of communityacquired IE. S. aureus as the causal agent of IE was the most important factor associated with in-hospital death in community-acquired IE (hazard ratio [HR], 2.82 [95% CI, 1.72‐4.61]) and the single factor in healthcare-associated IE (HR, 2.54 [95% CI, 1.33‐4.85]). Conclusions. S. aureus became both the leading cause and the most important prognostic factor of IE, and healthcare-associated IE appeared as a major subgroup of the disease.

Pathogenesis of Mucormycosis

Abstract: Mucormycosis is a life-threatening infection that occurs in patients who are immunocompromised because of diabetic ketoacidosis, neutropenia, organ transplantation, and/or increased serum levels of available iron. Because of the increasing prevalence of diabetes mellitus, cancer, and organ transplantation, the number of patients at risk for this deadly infection is increasing. Despite aggressive therapy, which includes disfiguring surgical debridement and frequently adjunctive toxic antifungal therapy, the overall mortality rate is high. New strategies to prevent and treat mucormycosis are urgently needed. Understanding the pathogenesis of mucormycosis and the host response to invading hyphae ultimately will provide targets for novel therapeutic interventions. In this supplement, we review the current knowledge about the virulence traits used by the most common etiologic agent of mucormycosis, Rhizopus oryzae. Because patients with elevated serum levels of available iron are uniquely susceptible to mucormycosis and these infections are highly angioinvasive, emphasis is placed on the ability of the organism to acquire iron from the host and on its interactions with endothelial cells lining blood vessels. Several promising therapeutic strategies in preclinical stages are identified.

Totally Drug-Resistant Tuberculosis in India

Abstract: To the Editor—Three years after extensively drug-resistant (XDR) tuberculosis was first described in 2006, Velayati et al [1] drew attention to the emergence of totally drug-resistant (TDR) tuberculosis in a cohort of 15 patients from Iran, resistant to all firstand second-line drugs. Since the first cases of XDR tuberculosis in India were reported from the P. D. Hinduja National Hospital and Medical Research Centre [2], physicians here have grappled with increasingly resistant strains of tuberculosis. We describe the first patients from India with TDR tuberculosis. Drug susceptibility testing (DST) was performed at the Hinduja Hospital, the city’s busiest referral laboratory and a Revised National Tuberculosis Control Programme (RNTCP) accredited

Burden of Clostridium difficile on the healthcare system.

Abstract: There are few high-quality studies of the costs of Clostridium difficile infection (CDI), and the majority of studies focus on the costs of CDI in acute-care facilities. Analysis of the best available data, from 2008, indicates that CDI may have resulted in $4.8 billion in excess costs in US acute-care facilities. Other areas of CDI-attributable excess costs that need to be investigated are costs of increased discharges to long-term care facilities, of CDI with onset in long-term care facilities, of recurrent CDI, and of additional adverse events caused by CDI.

Linezolid in methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a randomized, controlled study.

Abstract: Background. Post hoc analyses of clinical trial data suggested that linezolid may be more effective than vancomycin for treatment of methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia. This study prospectively assessed efficacy and safety of linezolid, compared with a dose-optimized vancomycin regimen, for treatment of MRSA nosocomial pneumonia. Methods. This was a prospective, double-blind, controlled, multicenter trial involving hospitalized adult patients with hospital-acquired or healthcare‐associated MRSA pneumonia. Patients were randomized to receive intravenous linezolid (600 mg every 12 hours) or vancomycin (15 mg/kg every 12 hours) for 7‐14 days. Vancomycin dose was adjusted on the basis of trough levels. The primary end point was clinical outcome at end of study (EOS) in evaluable per-protocol (PP) patients. Prespecified secondary end points included response in the modified intentto-treat (mITT) population at end of treatment (EOT) and EOS and microbiologic response in the PP and mITT populations at EOT and EOS. Survival and safety were also evaluated. Results. Of 1184 patients treated, 448 (linezolid, n 5 224; vancomycin, n 5 224) were included in the mITT and 348 (linezolid, n 5 172;vancomycin,n 5 176)inthePPpopulation.Inthe PP population, 95(57.6%)of165linezolidtreated patients and 81 (46.6%) of 174 vancomycin-treated patients achieved clinical success at EOS (95% confidence interval for difference, 0.5%‐21.6%; P 5 .042). All-cause 60-day mortality was similar (linezolid, 15.7%; vancomycin, 17.0%), as was incidence of adverse events. Nephrotoxicity occurred more frequently with vancomycin (18.2%; linezolid, 8.4%). Conclusions. For the treatment of MRSA nosocomial pneumonia, clinical response at EOS in the PP population was significantly higher with linezolid than with vancomycin, although 60-day mortality was similar.

IDSA Clinical Practice Guideline for Acute Bacterial Rhinosinusitis in Children and Adults

Abstract: Evidence-based guidelines for the diagnosis and initial management of suspected acute bacterial rhinosinusitis in adults and children were prepared by a multidisciplinary expert panel of the Infectious Diseases Society of America comprising clinicians and investigators representing internal medicine, pediatrics, emergency medicine, otolaryngology, public health, epidemiology, and adult and pediatric infectious disease specialties. Recommendations for diagnosis, laboratory investigation, and empiric antimicrobial and adjunctive therapy were developed.

Executive Summary: Clinical Practice Guideline for the Diagnosis and Management of Group A Streptococcal Pharyngitis: 2012 Update by the Infectious Diseases Society of America

Abstract: The guideline is intended for use by healthcare providers who care for adult and pediatric patients with group A streptococcal pharyngitis. The guideline updates the 2002 Infectious Diseases Society of America guideline and discusses diagnosis and management, and recommendations are provided regarding antibiotic choices and dosing. Penicillin or amoxicillin remain the treatments of choice, and recommendations are made for the penicillin-allergic patient, which now include clindamycin.

Hospitalizations Associated With Influenza and Respiratory Syncytial Virus in the United States, 1993–2008

Abstract: Influenza and respiratory syncytial virus (RSV) are important pathogens responsible for substantial morbidity and mortality almost every US winter. Influenza- and RSV-associated illnesses are difficult to count because the symptoms associated with infection are nonspecific, laboratory testing is not routine, and influenza and RSV codes are listed incompletely in administrative medical records. Recent prospective studies have enrolled persons seeking care for respiratory conditions and tested them for infection [1–6]; however, such studies are resource intensive and rarely conducted in multiple sites or over seasons. In contrast, modeling approaches using broad disease outcomes have been used to estimate the burden of influenza and RSV in large populations and over long periods [7–13], but these approaches generally focus on a single pathogen. A better understanding of the relative burdens of influenza and RSV in all age groups is important for prevention efforts, particularly to guide deliberations about the expansion of existing vaccination recommendations and the development of new vaccines. Annual influenza and RSV epidemics often overlap in temperate regions [12, 14], increasing the difficulty of modeling their effects, although their age-specific burdens do differ. Influenza is responsible for high rates of morbidity and mortality among older adults [7, 8, 10–13], whereas RSV has long been recognized as the most important respiratory viral pathogen in young children [4–6, 15, 16]. However, there is debate about the relative impact of influenza and RSV infections, particularly among adults aged ≥65 years [2]. A US study that jointly assessed influenza and RSV mortality estimated that 13.8 influenza- and 4.3 RSV-associated deaths occurred per 100000 persons annually during 1990–1999 [12]. This study also suggested that mortality associated with both influenza and RSV circulation disproportionately affected older adults [12]. Another US study estimated that influenza was responsible for 88 hospitalizations per 100000 persons from 1979 through 2001 [11], but it did not provide burden estimates for infants or estimates of RSV-associated hospitalizations. Using a 1% sample of all US hospitalizations, Holman et al estimated that 2740 RSV hospitalizations per 100000 infants occur annually [17]. Using laboratory-confirmed diagnoses, Fry et al [3] estimated 1087 RSV hospitalizations per 100000 infants occurred annually in rural Thailand. Other studies focused on US children aged <5 years have found that the influenza burden is lower than that of RSV in this age group [4–6]. We sought to estimate jointly overall and age-specific US hospitalization rates for influenza and RSV infections during many respiratory virus seasons to fill a data gap. We used complete state hospital discharge databases representing approximately 40% of the US population.

The Clinical Significance of Vancomycin Minimum Inhibitory Concentration in Staphylococcus aureus Infections: A Systematic Review and Meta-analysis

Abstract: Background Emerging data suggest that vancomycin may be less effective against serious methicillin-resistant Staphylococcus aureus (MRSA) infections with minimum inhibitory concentration (MIC) values at the higher end of the susceptibility range The purpose of this review is to examine the strength of these associations

Risk of Anal Cancer in HIV-Infected and HIV-Uninfected Individuals in North America

Abstract: adjusted rate ratios (RRs) of 80.3 (95% confidence interval [CI], 42.7‐151.1) for HIV-infected MSM and 26.7 (95% CI, 11.5‐61.7) for other HIV-infected men compared with HIV-uninfected men. HIV-infected women had an anal cancer rate of 30/100 000 person-years, and no cases were observed for HIV-uninfected women. In a multivariable Poisson regression model, among HIV-infected individuals, the risk was higher for MSM compared with other men (RR, 3.3; 95% CI, 1.8‐6.0), but no difference was observed comparing women with other men (RR, 1.0; 95% CI, 0.5‐2.2). In comparison with the period 2000‐2003, HIV-infected individuals had an adjusted RR of 0.5 (95% CI, .3‐.9) in 1996‐1999 and 0.9 (95% CI, .6‐1.2) in 2004‐2007. Conclusions. Anal cancer rates were substantially higher for HIV-infected MSM, other men, and women compared with HIV-uninfected individuals, suggesting a need for universal prevention efforts. Rates increased after the early antiretroviral therapy era and then plateaued.

Current Status of Clostridium difficile Infection Epidemiology

Abstract: The dramatic changes in the epidemiology of Clostridium difficile infection (CDI) during recent years, with increases in incidence and severity of disease in several countries, have made CDI a global public health challenge. Increases in CDI incidence have been largely attributed to the emergence of a previously rare and more virulent strain, BI/NAP1/027. Increased toxin production and high-level resistance to fluoroquinolones have made this strain a very successful pathogen in healthcare settings. In addition, populations previously thought to be at low risk are now being identified as having severe CDI. Recent genetic analysis suggests that C. difficile has a highly fluid genome with multiple mechanisms to modify its content and functionality, which can make C. difficile adaptable to environmental changes and potentially lead to the emergence of more virulent strains. In the face of these changes in the epidemiology and microbiology of CDI, surveillance systems are necessary to monitor trends and inform public health actions.

A Global Analysis of Mucormycosis in France: The RetroZygo Study (2005–2007)

Abstract: BACKGROUND: Mucormycosis is a deadly invasive fungal infection whose characteristics are only partially understood. METHODS: Data on mucormycosis obtained in France between 2005 and 2007 from 2 notification systems were merged. The 2008 European Organisation for Research and Treatment of Cancer/Mycoses Study Group definition criteria were applied and risk factors for death were analyzed by hazard ratios (HRs) calculated from the Cox proportional hazards regression model. RESULTS: A total of 101 cases (60 proven, 41 probable), mostly in men (58%) >50 years (mean age, 50.7 ± 19.9) were recorded. Hematological malignancies represented 50% (median time for occurrence, 8.8 months after disease onset), diabetes 23%, and trauma 18% of cases. Sites of infection were lungs (28%; 79% in hematology patients), rhinocerebral (25%; 64% in diabetic patients), skin (20%), and disseminated (18%). Median time between first symptoms and diagnosis was 2 weeks. The main fungal species were Rhizopus oryzae (32%) and Lichtheimia species (29%). In cases where the causative species was identified, R. oryzae was present in 85% of rhinocerebral forms compared with only 17% of nonrhinocerebral forms (P < .001). Treatment consisted of surgery in 59% and antifungals in 87% of cases (liposomal amphotericin B in 61%). Ninety-day survival was 56%; it was reduced in cases of dissemination compared with rhinocerebral (HR, 5.38 [2.0-14.1]; P < .001), pulmonary (HR, 2.2 [1.0-4.7]; P = .04), or skin localization (HR, 5.73 [1.9-17.5]; P = .002); survival was reduced in cases of hematological malignancies compared with diabetes mellitus (HR, 2.3 [1.0-5.2]; P < .05) or trauma (HR, 6.9 [1.6-28.6], P = .008) and if ≥2 underlying conditions (HR, 5.9 [1.8-19.0]; P = .004). Mucormycosis localization remained the only independent factor associated with survival. CONCLUSIONS: This 3-year study performed in one country shows the diverse clinical presentation of mucormycosis with a high prevalence of primary skin infection following trauma and a prognosis significantly influenced by localization.

Septic Shock Attributed to Candida Infection: Importance of Empiric Therapy and Source Control

Abstract: Background: Delayed treatment of candidemia has previously been shown to be an important determinant of patient outcome. However, septic shock attributed to Candida infection and its determinants of outcome have not been previously evaluated in a large patient population. Methods: A retrospective cohort study of hospitalized patients with septic shock and blood cultures positive for Candida species was conducted at Barnes-Jewish Hospital, a 1250-bed urban teaching hospital (January 2002-December 2010). Results: Two hundred twenty-four consecutive patients with septic shock and a positive blood culture for Candida species were identified. Death during hospitalization occurred among 155 (63.5%) patients. The hospital mortality rate for patients having adequate source control and antifungal therapy administered within 24 hours of the onset of shock was 52.8% (n = 142), compared to a mortality rate of 97.6% (n = 82) in patients who did not have these goals attained (P < .001). Multivariate logistic regression analysis demonstrated that delayed antifungal treatment (adjusted odds ratio [AOR], 33.75; 95% confidence interval [CI], 9.65-118.04; P = .005) and failure to achieve timely source control (AOR, 77.40; 95% CI, 21.52-278.38; P = .001) were independently associated with a greater risk of hospital mortality. Conclusions: The risk of death is exceptionally high among patients with septic shock attributed to Candida infection. Efforts aimed at timely source control and antifungal treatment are likely to be associated with improved clinical outcomes.

Efficacy, Safety, and Tolerability of Herpes Zoster Vaccine in Persons Aged 50–59 Years

Abstract: Background. Herpes zoster (HZ) adversely affects individuals aged 50‐59, but vaccine efficacy has not been assessed in this population. This study was designed to determine the efficacy, safety, and tolerability of zoster vaccine for preventing HZ in persons aged 50‐59 years. Methods. This was a randomized, double-blind, placebo-controlled study of 22 439 subjects aged 50‐59 years conducted in North America and Europe. Subjects were given 1 dose of licensed zoster vaccine (ZV) (Zostavax; Merck) and followed for occurrence of HZ for $1 year (mean, 1.3 years) postvaccination until accrual of $96 confirmed HZ cases (as determined by testing lesions swabs for varicella zoster virus DNA by polymerase chain reaction). Subjects were followed for all adverse events (AEs) from day 1 to day 42 postvaccination and for serious AEs (SAEs) through day 182 postvaccination. Results. The ZV reduced the incidence of HZ (30 cases in vaccine group, 1.99/1000 person-years vs 99 cases in placebo group, 6.57/1000 person-years). Vaccine efficacy for preventing HZ was 69.8% (95% confidence interval, 54.1‐80.6). AEs were reported by 72.8% of subjects in the ZV group and 41.5% in the placebo group, with the difference primarily due to higher rates of injection-site AEs and headache. The proportion of subjects reporting SAEs occurring within 42 days postvaccination (ZV, 0.6%; placebo, 0.5%) and 182 days postvaccination (ZV, 2.1%; placebo, 1.9%) was similar between groups. Conclusions. In subjects aged 50‐59 years, the ZV significantly reduced the incidence of HZ and was well tolerated.

Treatment of first recurrence of Clostridium difficile infection: fidaxomicin versus vancomycin.

Abstract: Recurrence of Clostridium difficile infection (CDI) occurs in approximately 25% of successfully treated patients. Two phase 3 randomized, double-blind trials were conducted at 154 sites in the United States, Canada, and Europe to compare fidaxomicin vs vancomycin in treating CDI. Patients with CDI received fidaxomicin 200 mg twice daily or vancomycin 125 mg 4 times daily for 10 days. The primary end point was clinical cure of CDI at end of treatment, and a secondary end point was recurrence during the 28 days following clinical cure. In all, 1164 subjects were enrolled, of which a subgroup of 128 in the per-protocol population had another recent episode of CDI prior to the CDI diagnosis at study enrollment. In the analysis of this subgroup, initial response to therapy was similar for both drugs (>90% cure). However, recurrence within 28 days occurred in 35.5% of patients treated with vancomycin and 19.7% of patients treated with fidaxomicin (-15.8% difference; 95% confidence interval, -30.4% to -0.3%; P = .045). Early recurrence (within 14 days) was reported in 27% of patients treated with vancomycin and 8% of patients treated with fidaxomicin (P = .003). In patients with a first recurrence of CDI, fidaxomicin was similar to vancomycin in achieving a clinical response at end of therapy but superior in preventing a second recurrence within 28 days.

Global burden of hepatitis C: considerations for healthcare providers in the United States.

Abstract: An estimated 2%–3% of the world’s population is living with hepatitis C virus (HCV) infection, and each year, >350 000 die of HCV-related conditions, including cirrhosis and liver cancer. The epidemiology and burden of HCV infection varies throughout the world, with country-specific prevalence ranging from 10%. In contrast to the United States and other developed countries, HCV transmission in developing countries frequently results from exposure to infected blood in healthcare and community settings. Hepatitis C prevention, care, and treatment programs must recognize country-specific epidemiology, which varies by setting and level of economic development. Awareness of the global epidemiology of HCV infection is important for US healthcare providers treating foreign-born patients from countries where HCV infection is endemic and for counseling patients who travel to these countries. Countries with a high burden of HCV infection also would benefit from establishing comprehensive prevention, care, and treatment programs. Globally, an estimated 130–170 million persons (2%–3% of the world’s population) are living with hepatitis C virus (HCV) infection [1]. This infection, particularly in its chronic form, is associated with sizable morbidity and mortality. More than 350 000 deaths are attributed to HCV infection each year, most of which are caused by liver cirrhosis and hepatocellular carcinoma (HCC) [2]. An estimated 27% of cirrhosis and 25% of HCC can be attributed to hepatitis C worldwide, and disease rates can be even more substantial in countries with a high burden of infection. For example, in Japan, up to 90% of all reported cases of HCC are caused by HCV infection [2].

β-Lactam/β-Lactam Inhibitor Combinations for the Treatment of Bacteremia Due to Extended-Spectrum β-Lactamase–Producing Escherichia coli: A Post Hoc Analysis of Prospective Cohorts

Abstract: Background Extended-spectrum s-lactamase-producing Escherichia coli (ESBL-EC) is an important cause of invasive infections. Alternatives to carbapenems--considered the drugs of choice--are needed because of the emergence of carbapenemase-producing enterobacteria. The efficacy of s-lactam/s-lactam inhibitors (BLBLI) in such infections is controversial. Methods The authors performed a post hoc analysis of patients with bloodstream infections due to ESBL-EC from 6 published prospective cohorts. Mortality and length of hospital stay in patients treated with an active BLBLI (amoxicillin-clavulanic acid [AMC] and piperacillin-tazobactam [PTZ]) or carbapenem were compared in 2 cohorts: the empirical therapy cohort (ETC) and the definitive therapy cohort (DTC). Confounding was controlled by multivariate analysis; for patients in the ETC, a propensity score for receiving carbapenem was also used. Results The ETC included 103 patients (BLBLI, 72; carbapenem, 31), and the DTC included 174 (BLBLI, 54; carbapenem, 120). Mortality rates at day 30 for those treated with BLBLI versus carbapenems were 9.7% versus 19.4% for the ETC and 9.3% versus 16.7% for the DTC, respectively (P > .2, log-rank test). After adjustment for confounders, no association was found between either empirical therapy with BLBLI (adjusted hazard ratio [HR], 1.14; 95% confidence interval [CI], .29-4.40; P = .84) or definitive therapy (adjusted HR, 0.76; 95% CI, .28-2.07; P = .5) and increased mortality. Furthermore, BLBLI therapy, with respect to carbapenem, was not found to influence length of hospital stay. Conclusions These results suggest that AMC and PTZ are suitable alternatives to carbapenems for treating patients with bloodstream infections due to ESBL-EC if active in vitro and would be particularly useful as definitive therapy.

Changes in Incidence and Antifungal Drug Resistance in Candidemia: Results From Population-Based Laboratory Surveillance in Atlanta and Baltimore, 2008–2011

Abstract: Bloodstream infections (BSIs) caused by Candida species, also known as candidemia, are an important public health problem in the United States. Candida species are among the most common causes of BSIs and are associated with high morbidity and mortality, as well as increases in hospital cost and length of stay [1–5]. Although most reports that describe the epidemiology of candidemia are from individual institutions or among specific patient groups, few reports in the United States have described the epidemiology of candidemia at a population level. Population-based data are important for describing infections in whole populations and across the entire spectrum of healthcare settings, and can be used to determine group-specific incidence rates to monitor and compare rates of infection over time. Previous population-based surveillance performed by the Centers for Disease Control and Prevention (CDC) and partners in Atlanta, Georgia (1992–1993), and Baltimore, Maryland (1998–2000), described incidence rates of 8.7 per 100 000 population in Atlanta and 24 per 100 000 population in Baltimore [6, 7]. During both surveillance periods, drug resistance to fluconazole was low: 3% of isolates were resistant in 1992, and 3.7% were resistant in 1998 [6–8]. Over the past decade, Candida species with reduced fluconazole susceptibility, such as Candida glabrata, have become more prevalent in some patient populations [8–12]. The newest class of antifungal medications, the echinocandins, are considered first-line empiric therapy for candidemia, and there are reports of echinocandin-resistant invasive infection [13, 14]. To evaluate changes in the epidemiology and antifungal drug resistance of candidemia, we conducted population-based prospective surveillance in metropolitan Atlanta, Georgia, and Baltimore City and County, Maryland, 2 areas where prior surveillance had been conducted.

Increasing Rates of Vibriosis in the United States, 1996–2010: Review of Surveillance Data From 2 Systems

Abstract: Background The Centers for Disease Control and Prevention monitors vibriosis through 2 surveillance systems: the nationwide Cholera and Other Vibrio Illness Surveillance (COVIS) system and the 10-state Foodborne Diseases Active Surveillance Network (FoodNet). COVIS conducts passive surveillance and FoodNet conducts active surveillance for laboratory-confirmed Vibrio infections. Methods We summarized Vibrio infections (excluding toxigenic V. cholerae O1 and O139) reported to COVIS and FoodNet from 1996 through 2010. For each system, we calculated incidence rates using US Census Bureau population estimates for the surveillance area. Results From 1996 to 2010, 7700 cases of vibriosis were reported to COVIS and 1519 to FoodNet. Annual incidence of reported vibriosis per 100,000 population increased from 1996 to 2010 in both systems, from 0.09 to 0.28 in COVIS and from 0.15 to 0.42 in FoodNet. The 3 commonly reported Vibrio species were V. parahaemolyticus, V. vulnificus, and V. alginolyticus; both surveillance systems showed that the incidence of each increased. In both systems, most hospitalizations and deaths were caused by V. vulnificus infection, and most patients were white men. The number of cases peaked in the summer months. Conclusions Surveillance data from both COVIS and FoodNet indicate that the incidence of vibriosis increased from 1996 to 2010 overall and for each of the 3 most commonly reported species. Epidemiologic patterns were similar in both systems. Current prevention efforts have failed to prevent increasing rates of vibriosis; more effective efforts will be needed to decrease rates.

Systemic Antibiotic Therapy for Chronic Osteomyelitis in Adults

Abstract: The standard recommendation for treating chronic osteomyelitis is 6 weeks of parenteral antibiotic therapy. However, oral antibiotics are available that achieve adequate levels in bone, and there are now more published studies of oral than parenteral antibiotic therapy for patients with chronic osteomyelitis. Oral and parenteral therapies achieve similar cure rates; however, oral therapy avoids risks associated with intravenous catheters and is generally less expensive, making it a reasonable choice for osteomyelitis caused by susceptible organisms. Addition of adjunctive rifampin to other antibiotics may improve cure rates. The optimal duration of therapy for chronic osteomyelitis remains uncertain. There is no evidence that antibiotic therapy for >4–6 weeks improves outcomes compared with shorter regimens. In view of concerns about encouraging antibiotic resistance to unnecessarily prolonged treatment, defining the optimal route and duration of antibiotic therapy and the role of surgical debridement in treating chronic osteomyelitis are important, unmet needs.

Oral Transmission of Chagas Disease

Abstract: Chagas disease is now an active disease in the urban centers of countries of nonendemicity and endemicity because of congenital and blood and/or organ transplantation transmissions and the reactivation of the chronic disease in smaller scale than vectorial transmission, reported as controlled in countries of endemicity. Oral transmission of Chagas disease has emerged in unpredictable situations in the Amazon region and, more rarely, in areas of nonendemicity where the domiciliary triatomine cycle was under control because of exposition of the food to infected triatomine and contaminated secretions of reservoir hosts. Oral transmission of Chagas disease is considered when >1 acute case of febrile disease without other causes is linked to a suspected food and should be confirmed by the presence of the parasite after direct microscopic examination of the blood or other biological fluid sample from the patient.

The Effect of Therapeutic Drug Monitoring on Safety and Efficacy of Voriconazole in Invasive Fungal Infections: A Randomized Controlled Trial

Abstract: Background. Blood levels of voriconazole, a first line therapy for invasive aspergillosis, may correlate with adverse events and treatment response. However, no randomized controlled studies have been conducted to evaluate the clinical utility of routine therapeutic drug monitoring (TDM) of voriconazole. This study aimed to determine whether routine TDM of voriconazole reduces drug adverse events or improves treatment response in invasive fungal infections. Methods. This was a randomized, assessor-blinded, controlled, single center trial. One hundred ten adult patients were randomly assigned to TDM or non-TDM groups. In the TDM group, voriconazole dosage was adjusted (target range, 1.0–5.5 mg/L) according to the serum trough level measured on the fourth day after initiation of voriconazole. The non-TDM group received a fixed, standard dosage. Voriconazole-related adverse events were monitored, and treatment response was assessed three months after the initiation of therapy. Results. Baseline characteristics including the CYP2C19 genotype were comparable between the two groups. While the incidence of adverse events was not different between the TDM group and the non-TDM group (both 42%; P= .97), the proportion of voriconazole discontinuation due to adverse events was significantly lower in the TDM group than in the non-TDM group (4% vs 17%; P= .02). A complete or partial response was observed in 81% (30 of 37) of patients in the TDM group compared to 57% (20 of 34) in the non-TDM group (P= .04). Conclusions. Routine TDM of voriconazole may reduce drug discontinuation due to adverse events and improve the treatment response in invasive fungal infections. Clinical Trial Registration. NCT00890708.

The Global Enteric Multicenter Study (GEMS) of Diarrheal Disease in Infants and Young Children in Developing Countries: Epidemiologic and Clinical Methods of the Case/Control Study

Abstract: Background. Diarrhea is a leading cause of illness and death among children aged <5 years in developing countries. This paper describes the clinical and epidemiological methods used to conduct the Global Enteric Multicenter Study (GEMS), a 3-year, prospective, age-stratified, case/control study to estimate the population-based burden, microbiologic etiology, and adverse clinical consequences of acute moderate-to-severe diarrhea (MSD) among a censused population of children aged 0–59 months seeking care at health centers in sub-Saharan Africa and South Asia. Methods. GEMS was conducted at 7 field sites, each serving a population whose demography and healthcare utilization practices for childhood diarrhea were documented. We aimed to enroll 220 MSD cases per year from selected health centers serving each site in each of 3 age strata (0–11, 12–23, and 24–59 months), along with 1–3 matched community controls. Cases and controls supplied clinical, epidemiologic, and anthropometric data at enrollment and again approximately 60 days later, and provided enrollment stool specimens for identification and characterization of potential diarrheal pathogens. Verbal autopsy was performed if a child died. Analytic strategies will calculate the fraction of MSD attributable to each pathogen and the incidence, financial costs, nutritional consequences, and case fatality overall and by pathogen. Conclusions. When completed, GEMS will provide estimates of the incidence, etiology, and outcomes of MSD among infants and young children in sub-Saharan Africa and South Asia. This information can guide development and implementation of public health interventions to diminish morbidity and mortality from diarrheal diseases.