Showing papers in "Clinical Infectious Diseases in 2014"

Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious Diseases Society of America

Abstract: A panel of national experts was convened by the Infectious Diseases Society of America (IDSA) to update the 2005 guidelines for the treatment of skin and soft tissue infections (SSTIs). The panel's recommendations were developed to be concordant with the recently published IDSA guidelines for the treatment of methicillin-resistant Staphylococcus aureus infections. The focus of this guideline is the diagnosis and appropriate treatment of diverse SSTIs ranging from minor superficial infections to life-threatening infections such as necrotizing fasciitis. In addition, because of an increasing number of immunocompromised hosts worldwide, the guideline addresses the wide array of SSTIs that occur in this population. These guidelines emphasize the importance of clinical skills in promptly diagnosing SSTIs, identifying the pathogen, and administering effective treatments in a timely fashion.

2013 IDSA Clinical Practice Guideline for Vaccination of the Immunocompromised Host

Abstract: An international panel of experts prepared an evidenced-based guideline for vaccination of immunocompromised adults and children. These guidelines are intended for use by primary care and subspecialty providers who care for immunocompromised patients. Evidence was often limited. Areas that warrant future investigation are highlighted.

Executive Summary: Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious Diseases Society of America

Abstract: A panel of national experts was convened by the Infectious Diseases Society of America (IDSA) to update the 2005 guidelines for the treatment of skin and soft tissue infections (SSTIs). The panel's recommendations were developed to be concordant with the recently published IDSA guidelines for the treatment of methicillin-resistant Staphylococcus aureus infections. The focus of this guideline is the diagnosis and appropriate treatment of diverse SSTIs ranging from minor superficial infections to life-threatening infections such as necrotizing fasciitis. In addition, because of an increasing number of immunocompromised hosts worldwide, the guideline addresses the wide array of SSTIs that occur in this population. These guidelines emphasize the importance of clinical skills in promptly diagnosing SSTIs, identifying the pathogen, and administering effective treatments in a timely fashion.

Executive Summary: 2013 IDSA Clinical Practice Guideline for Vaccination of the Immunocompromised Host

Abstract: An international panel of experts prepared an evidenced-based guideline for vaccination of immunocompromised adults and children. These guidelines are intended for use by primary care and subspecialty providers who care for immunocompromised patients. Evidence was often limited. Areas that warrant future investigation are highlighted.

DALI: Defining Antibiotic Levels in Intensive Care Unit Patients: Are Current β-Lactam Antibiotic Doses Sufficient for Critically Ill Patients?

Abstract: Background. Morbidity and mortality for critically ill patients with infections remains a global healthcare problem. We aimed to determine whether ?-lactam antibiotic dosing in critically ill patients achieves concentrations associated with maximal activity and whether antibiotic concentrations affect patient outcome.Methods. This was a prospective, multinational pharmacokinetic point-prevalence study including 8 ?-lactam antibiotics. Two blood samples were taken from each patient during a single dosing interval. The primary pharmacokinetic/pharmacodynamic targets were free antibiotic concentrations above the minimum inhibitory concentration (MIC) of the pathogen at both 50% (50% f TMIC) and 100% (100% f T MIC) of the dosing interval. We used skewed logistic regression to describe the effect of antibiotic exposure on patient outcome.Results. We included 384 patients (361 evaluable patients) across 68 hospitals. The median age was 61 (interquartile range [IQR], 48-73) years, the median Acute Physiology and Chronic Health Evaluation II score was 18 (IQR, 14-24), and 65% of patients were male. Of the 248 patients treated for infection, 16% did not achieve 50% f TMIC and these patients were 32% less likely to have a positive clinical outcome (odds ratio [OR], 0.68; P =. 009). Positive clinical outcome was associated with increasing 50% f TMIC and 100% f TMIC ratios (OR, 1.02 and 1.56, respectively; P

Protection by BCG Vaccine Against Tuberculosis: A Systematic Review of Randomized Controlled Trials

Abstract: BACKGROUND: Randomized trials assessing BCG vaccine protection against tuberculosis have widely varying results, for reasons that are not well understood. METHODS: We examined associations of trial setting and design with BCG efficacy against pulmonary and miliary or meningeal tuberculosis by conducting a systematic review, meta-analyses, and meta-regression. RESULTS: We identified 18 trials reporting pulmonary tuberculosis and 6 reporting miliary or meningeal tuberculosis. Univariable meta-regression indicated efficacy against pulmonary tuberculosis varied according to 3 characteristics. Protection appeared greatest in children stringently tuberculin tested, to try to exclude prior infection with Mycobacterium tuberculosis or sensitization to environmental mycobacteria (rate ratio [RR], 0.26; 95% confidence interval [CI], .18-.37), or infants (RR, 0.41; 95% CI, .29-.58). Protection was weaker in children not stringently tested (RR, 0.59; 95% CI, .35-1.01) and older individuals stringently or not stringently tested (RR, 0.88; 95% CI, .59-1.31 and RR, 0.81; 95% CI, .55-1.22, respectively). Protection was higher in trials further from the equator where environmental mycobacteria are less and with lower risk of diagnostic detection bias. These associations were attenuated in a multivariable model, but each had an independent effect. There was no evidence that efficacy was associated with BCG strain. Protection against meningeal and miliary tuberculosis was also high in infants (RR, 0.1; 95% CI, .01-.77) and children stringently tuberculin tested (RR, 0.08; 95% CI, .03-.25). CONCLUSIONS: Absence of prior M. tuberculosis infection or sensitization with environmental mycobacteria is associated with higher efficacy of BCG against pulmonary tuberculosis and possibly against miliary and meningeal tuberculosis. Evaluations of new tuberculosis vaccines should account for the possibility that prior infection may mask or block their effects.

Cross-sectional comparison of the prevalence of age-associated comorbidities and their risk factors between HIV-infected and uninfected individuals: the AGEhIV Cohort Study

Abstract: Human immunodeficiency virus (HIV)-infected individuals may be at increased risk of age-associated noncommunicable comorbidities (AANCCs). Cross-sectional analyses of AANCC prevalence (including cardiovascular, metabolic, pulmonary, renal, bone, and malignant disease) and risk factors in a prospective cohort study of HIV type 1-infected individuals and HIV-uninfected controls, who were aged ≥45 years and comparable regarding most lifestyle and demographic factors. HIV-infected participants (n = 540) had a significantly higher mean number of AANCCs than controls (n = 524) (1.3 [SD, 1.14] vs 1.0 [SD, 0.95]; P < .001), with significantly more HIV-infected participants having ≥1 AANCC (69.4% vs 61.8%; P = .009). Hypertension, myocardial infarction, peripheral arterial disease, and impaired renal function were significantly more prevalent among HIV-infected participants. Risk of AANCC by ordinal logistic regression was independently associated with age, smoking, positive family history for cardiovascular/metabolic disease, and higher waist-to-hip ratio, but also with HIV infection (odds ratio, 1.58 [95% confidence interval, 1.23-2.03]; P < .001). In those with HIV, longer exposure to CD4 counts <200 cells/µL, and, to a lesser extent, higher levels of high-sensitivity C-reactive protein and soluble CD14, and longer prior use of high-dose ritonavir (≥400 mg/24 hours) were each also associated with a higher risk of AANCCs. All AANCCs were numerically more prevalent, with peripheral arterial, cardiovascular disease, and impaired renal function significantly so, among HIV-infected participants compared with HIV-uninfected controls. Besides recognized cardiovascular risk factors, HIV infection and longer time spent with severe immunodeficiency increased the risk of a higher composite AANCC burden. There was a less pronounced contribution from residual inflammation, immune activation, and prior high-dose ritonavir use

Core Elements of Hospital Antibiotic Stewardship Programs From the Centers for Disease Control and Prevention

Abstract: The proven benefits of antibiotic stewardship programs (ASPs) for optimizing antibiotic use and minimizing adverse events, such as Clostridium difficile and antibiotic resistance, have prompted the Centers for Disease Control and Prevention (CDC) to recommend that all hospitals have an ASP. This article summarizes Core Elements of Hospital Antibiotic Stewardship Programs, a recently released CDC document focused on defining the infrastructure and practices of coordinated multidisciplinary programs to improve antibiotic use and patient care in US hospitals.

Emerging Epidemic of Hepatitis C Virus Infections Among Young Nonurban Persons Who Inject Drugs in the United States, 2006–2012

Abstract: Background Reports of acute hepatitis C in young persons in the United States have increased. We examined data from national surveillance and supplemental case follow-up at selected jurisdictions to describe the US epidemiology of hepatitis C virus (HCV) infection among young persons (aged ≤30 years). Methods We examined trends in incidence of acute hepatitis C among young persons reported to the Centers for Disease Control and Prevention (CDC) during 2006-2012 by state, county, and urbanicity. Sociodemographic and behavioral characteristics of HCV-infected young persons newly reported from 2011 to 2012 were analyzed from case interviews and provider follow-up at 6 jurisdictions. Results From 2006 to 2012, reported incidence of acute hepatitis C increased significantly in young persons-13% annually in nonurban counties (P = .003) vs 5% annually in urban counties (P = .028). Thirty (88%) of 34 reporting states observed higher incidence in 2012 than 2006, most noticeably in nonurban counties east of the Mississippi River. Of 1202 newly reported HCV-infected young persons, 52% were female and 85% were white. In 635 interviews, 75% of respondents reported injection drug use. Of respondents reporting drug use, 75% had abused prescription opioids, with first use on average 2.0 years before heroin. Conclusions These data indicate an emerging US epidemic of HCV infection among young nonurban persons of predominantly white race. Reported incidence was higher in 2012 than 2006 in at least 30 states, with largest increases in nonurban counties east of the Mississippi River. Prescription opioid abuse at an early age was commonly reported and should be a focus for medical and public health intervention.

Vancomycin, Metronidazole, or Tolevamer for Clostridium difficile Infection: Results From Two Multinational, Randomized, Controlled Trials

Abstract: Background. Clostridium difficile infection (CDI) is a common complication of antibiotic therapy that is treated with antibiotics, contributing to ongoing disruption of the colonic microbiota and CDI recurrence. Two multinational trials were conducted to compare the efficacy of tolevamer, a nonantibiotic, toxin-binding polymer, with vancomycin and metronidazole. Methods. Patients with CDI were randomly assigned in a 2:1:1 ratio to oral tolevamer 9 g (loading dose) followed by 3 g every 8 hours for 14 days, vancomycin 125 mg every 6 hours for 10 days, or metronidazole 375 mg every 6 hours for 10 days. The primary endpoint was clinical success, defined as resolution of diarrhea and absence of severe abdominal discomfort for more than 2 consecutive days including day 10. Results. In a pooled analysis, 563 patients received tolevamer, 289 received metronidazole, and 266 received vancomycin. Clinical success of tolevamer was inferior to both metronidazole and vancomycin (P< .001), and metronidazole was inferior to vancomycin (P= .02; 44.2% [n = 534], 72.7% [n = 278], and 81.1% [n = 259], respectively). Clinical success in patients with severe CDI who received metronidazole was 66.3% compared with vancomycin, which was 78.5%. (P = .059). A post-hoc multivariate analysis that excluded tolevamer found 3 factors that were strongly associated with clinical success: vancomycin treatment, treatment-naive status, and mild or moderate CDI severity. Adverse events were similar among the treatment groups. Conclusions. Tolevamer was inferior to antibiotic treatment of CDI, and metronidazole was inferior to vancomycin. Trial Registration. clinicaltrials.gov NCT00106509 and NCT00196794.

Primary Care Guidelines for the Management of Persons Infected With HIV: 2013 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 2009. The guidelines are intended for use by healthcare providers who care for HIV-infected patients. Since 2009, 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, HIV-infected persons are increasingly developing common health problems that also affect the general population. Some of these conditions may be related to HIV infection itself or its treatment. HIV-infected persons should be managed and monitored for all relevant age- and sex-specific health problems. New information based on publications from the period 2009-2013 has been incorporated into this document.

Fecal Microbiota Transplant for Relapsing Clostridium difficile Infection Using a Frozen Inoculum From Unrelated Donors: A Randomized, Open-Label, Controlled Pilot Study

Abstract: Recurrent and refractory Clostridium difficile infection (CDI) is a growing medical concern, with a recent dramatic increase in the number of patients globally [1–4]. In the United States, the incidence of CDI has tripled over the last 15 years [3]. Response to standard antimicrobial therapy with oral vancomycin or metronidazole is suboptimal, with CDI recurring in up to 30% of individuals treated for a first episode. After 2 or more episodes of CDI, the estimated risk for subsequent recurrence exceeds 60% with antimicrobial therapy [3, 5–8]. Often, patients with recurrent CDI are treated with prolonged administration of oral vancomycin with tapering of the medication over many months, but this approach is poorly studied. The emergence of a virulent strain of the organism (NAP1/BI/027) has been associated with even higher rates of treatment failure [9, 10]. The consequences of recurrence can be devastating, resulting in life-threatening illness, frequent hospitalizations, and possible surgical interventions. In addition to individual morbidity and mortality, CDI taxes the medical system by requiring patient cohorting, leading to bed closures, delay of discharge, and additional contact precautions. Although the illness is toxin-mediated, overgrowth of the organism in the setting of dysbiosis is thought to be a key inciting event. Failure to reconstitute normal flora was shown to be a factor in severe, recurrent, and prolonged illness [11]. Fecal microbiota transplant (FMT)—reconstitution of normal flora by a stool transplant from a healthy individual—has been a successful therapeutic approach to recurrent/refractory CDI in animal studies [12], numerous case series [13–18], and, more recently, a single randomized clinical trial [19]. Even though an overall CDI resolution rate of about 90% has repeatedly been reported in published reviews and meta-analyses [20–23], practical and aesthetic barriers have hindered the widespread use of FMT to date. Recruitment and screening of donors is a lengthy process associated with significant costs, thus preventing the use of FMT in acute situations. Establishing a repository of prescreened frozen donor stools could make this treatment available for a wider population. Furthermore, many questions remain regarding the optimal protocol donor screening, sample processing, route of administration, and amount of fecal material instilled. In the current study, we aimed to investigate the clinical outcomes of FMT for refractory or relapsing CDI using a frozen suspension from unrelated donors by both upper and lower gastrointestinal routes.

Vertical Transmission of Hepatitis C Virus: Systematic Review and Meta-analysis

Abstract: Background. We conducted a systematic review of estimates of hepatitis C virus (HCV) vertical transmission risk to update current estimates published more than a decade ago. Methods. PubMed and Embase were searched and 109 articles were included. Pooled estimates of risk were generated for children born to HCV antibody–positive and viremic women, aged ≥18 months, separately by maternal human immunodeficiency virus (HIV) coinfection. Results. Meta-analysis of the risk of vertical HCV infection to children of HCV antibody–positive and RNApositivewomen was 5.8% (95% confidence interval [CI], 4.2%–7.8%) forchildren of HIV-negativewomen and 10.8% (95% CI, 7.6%–15.2%) for children of HIV-positive women. The adjusted meta-regression model explained 51% of the between-study variation in the 25 included risk estimates. Maternal HIV coinfection was the most important determinant of vertical transmission risk (adjusted odds ratio, 2.56 [95% CI, 1.50–4.43]). Additional methodological (follow-up rate and definition of infection in children) and risk factors independently predicted HCV infection and need to be captured and reported by future studies of vertical transmission. Studies assessing the contribution of nonvertical exposures in early childhood to HCV prevalence among children at risk of vertical transmission are needed. Conclusions. More than 1 in every 20 children delivered by HCV chronically infected women are infected, highlighting that vertical transmission likely constitutes the primary transmission route among children. These updated estimates are a basis for decision making in prioritization of research into risk-reducing measures, and inform case management in clinical settings, especially for HIV-positive women in reproductive age.

Lyme Disease Testing by Large Commercial Laboratories in the United States

Abstract: Background Laboratory testing is helpful when evaluating patients with suspected Lyme disease (LD). A two-tiered antibody testing approach is recommended, but single-tier and non-validated tests are also used. We conducted a survey of large commercial laboratories in the United States to assess laboratory practices. We used these data to estimate the cost of testing and number of infections among patients from whom specimens were submitted.

Executive Summary: Primary Care Guidelines for the Management of Persons Infected With HIV: 2013 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 2009. The guidelines are intended for use by healthcare providers who care for HIV-infected patients. Since 2009, 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, HIV-infected persons are increasingly developing common health problems that also affect the general population. Some of these conditions may be related to HIV infection itself or its treatment. HIV-infected persons should be managed and monitored for all relevant age- and sex-specific health problems. New information based on publications from the period 2009-2013 has been incorporated into this document.

Lower Pill Burden and Once-Daily Antiretroviral Treatment Regimens for HIV Infection: A Meta-Analysis of Randomized Controlled Trials

Abstract: Background. Contemporary antiretroviral treatment regimens are simpler than in the past, with lower pill burden and once-daily dosing frequency common. We performed a meta-analysis of randomized controlled trials (RCTs) to investigate the impact of pill burden and once-daily vs twice-daily dosing on ART adherence and virological outcomes. Methods. A literature search of 4 electronic databases through 31 March 2013 was used. RCTs comparing once-daily vs twice-daily ART regimens that also reported on adherence and virological suppression were included. Study design, study population characteristics, intervention, outcome measures, and study quality were extracted. Study quality was rated using the Cochrane risk-of-bias tool. Results. Nineteen studies met our inclusion criteria (N = 6312 adult patients). Higher pill burden was associated with both lower adherence rates (P = .004) and worse virological suppression (P < .0001) in both once-daily and twice-daily subgroups, although the association with adherence in the once-daily subgroup was not statistically significant. The average adherence was modestly higher in once-daily regimens than twice-daily regimens (weighted mean difference = 2.55%; 95% confidence interval [CI], 1.23 to 3.87; P = .0002). Patients on once-daily regimens did not achieve virological suppression more frequently than patients on twice-daily regimens (relative risk [RR] = 1.01; 95% CI, 0.99 to 1.03; P = .50). Both adherence and viral load suppression decreased over time, but adherence decreased less with once-daily dosing than with twice-daily dosing. Conclusions. Lower pill burden was associated with both better adherence and virological suppression. Adherence, but not virological suppression, was slightly better with once- vs twice-daily regimens.

Influenza Vaccine Effectiveness in the 2011–2012 Season: Protection Against Each Circulating Virus and the Effect of Prior Vaccination on Estimates

Abstract: (See the editorial commentary by Neuzil and Victor on pages 328–9.) Influenza vaccines are unique in requiring regular changes in composition to match the antigenic drift of the circulating virus strains [1]. They currently are recommended annually in the United States for all persons aged ≥6 months [2] and are composed of 3 strains representing influenza A (H3N2), A (H1N1), and B viruses, some of which may be new in a particular year and some of which may not. Because 2 distinct lineages of type B circulate, strains from both will soon be incorporated into what will then be a quadrivalent vaccine [3]. There is ample evidence that influenza vaccine effectiveness (VE) varies not only by virus type (subtype) but also from year to year [4]. A number of explanations for these variations have been suggested, including antigenic match between vaccine and circulating strains, the age and health status of vaccine recipients, and the time between vaccine receipt and occurrence of the seasonal outbreak. To monitor variation in VE, many countries have begun to conduct annual evaluations [5–9]. Various observational methods have been used, but most involve laboratory confirmation of illnesses as influenza and documentation of influenza vaccine receipt. Since the 2008–2009 influenza season, multiple centers in the United States have collaborated annually to estimate VE through the Influenza Vaccine Effectiveness (Flu VE) Network. This network examines the effectiveness of influenza vaccines in preventing medically attended acute respiratory illnesses caused by influenza. The network has quantified vaccine protection during seasonal outbreaks and has also demonstrated the effectiveness of the H1N1 pandemic vaccine once it became available in 2009 [5, 6]. We report here estimates of effectiveness of the 2011–2012 influenza vaccines, with special reference to protection against each circulating influenza virus and the effect of prior vaccination on estimates [10]. The influenza season was mild overall and peaked nationally in March 2012 with circulation of type A (H3N2) and A (H1N1) pdm09 viruses, plus type B viruses from both lineages [11].

The MAL-ED Study: A Multinational and Multidisciplinary Approach to Understand the Relationship Between Enteric Pathogens, Malnutrition, Gut Physiology, Physical Growth, Cognitive Development, and Immune Responses in Infants and Children Up to 2 Years of Age in Resource-Poor Environments

Abstract: MILLER, Mark ; GOTTLIEB, Michael ; BHUTTA, Zulfiqar ; KANG, Gagandeep ; JOHN, Sushil ; KOSEK, Margaret ; LIMA, Aldo A. M. ; ORIA, Reinaldo ; SHRESTHA, Sanjaya Kumar ; SHRESTHA, Prakash Sunder ; BESSONG, Pascal ; AHMED, Tahmeed ; HAQUE, Rashidul ; SVENSE, Erling ; CAULFIELD, Laura ; MURRAY-KOL, Laura ; BLACK, Robert ; GUERRANT, Richard ; PETRIF, William ; HOUPTH, Eric ; CONCANNON, Patrick ; RICH, Stephen ; DILLINGHAM, Rebecca ; MASON, Carl J. ; BODHIDATTA, Ladaporn ; GORDON, Jeffrey I. ; KNIGH, Rob ; WUK, Felicia. The MAL-ED study : a multinational and multidisciplinary approach to understand the relationship between enteric pathogens, malnutrition, gut physiology, physical growth, cognitive development, and immune responses in infants and children up to 2 years of age in resource-poor environments. Clinical Infectious Diseases, v. 59, p. S193-S206, 2014.

Hospital-Associated Outbreak of Middle East Respiratory Syndrome Coronavirus: A Serologic, Epidemiologic, and Clinical Description

Abstract: In April 2012, the Jordan Ministry of Health (JMoH) investigated a cluster of 13 suspected pneumonia cases among healthcare personnel, of which 2 were fatal, at a hospital in the city of Zarqa [1]. Despite testing for multiple potential pathogens, the investigation did not identify a known etiology for these infections. Following the discovery of Middle East respiratory syndrome coronavirus (MERS-CoV) in September 2012 [2], specimens from the 2 fatal cases in Jordan were retrospectively tested and both yielded positive results for MERS-CoV by real-time reverse transcription polymerase chain reaction (rRT-PCR), and were reported to the World Health Organization (WHO). These were the first confirmed human cases of infection with this emergent virus, which continues to appear as sporadic cases and clusters internationally, and which is now the focus of worldwide public health investigation and response [3, 4]. Using newly developed serologic assays to determine MERS-CoV antibody responses among case contacts in this outbreak, epidemiologists from the JMoH, US Centers for Disease Control and Prevention (CDC), and regional partners conducted a retrospective seroepidemiologic investigation to (1) confirm whether surviving outbreak members had presence of antibodies to MERS-CoV, (2) ascertain whether viral transmission occurred among household contacts or to other healthcare personnel, and (3) describe the clinical features of all detected MERS-CoV infections in Jordan.

Methicillin-resistant Staphylococcus aureus: an evolving pathogen.

Abstract: The horizontal transmission of methicillin resistance to Staphylococcus aureus (MRSA) in hospital and community settings, and growing prevalence of these strains, presents a significant clinical challenge to the management of serious infections worldwide. While infection control initiatives have stemmed the rising prevalence, MRSA remains a significant pathogen. More recently, evidence that MRSA is becoming resistant to glycopeptides and newer therapies raises concern about the use of these therapies in clinical practice. Vancomycin resistance has become evident in select clinical settings through rising MICs, growing awareness of heteroresistance, and emergence of intermediate-resistant and fully resistant strains. While resistance to linezolid and daptomycin remains low overall, point mutations leading to resistance have been described for linezolid, and horizontal transmission of cfr-mediated resistance to linezolid has been reported in clinical isolates. These resistance trends for newer therapies highlight the ongoing need for new and more potent antimicrobial therapies.

Determinants of Mortality in a Combined Cohort of 501 Patients With HIV-Associated Cryptococcal Meningitis: Implications for Improving Outcomes

Abstract: Background. Cryptococcal meningitis (CM) is a leading cause of death in individuals infected with human immunodeficiency virus (HIV). Identifying factors associated with mortality informs strategies to improve outcomes. Methods. Five hundred one patients with HIV-associated CM were followed prospectively for 10 weeks during trials in Thailand, Uganda, Malawi, and South Africa. South African patients (n = 266) were followed for 1 year. Similar inclusion/exclusion criteria were applied at all sites. Logistic regression identified baseline variables independently associated with mortality. Results. Mortality was 17% at 2 weeks and 34% at 10 weeks. Altered mental status (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.7–5.9), high cerebrospinal fluid (CSF) fungal burden (OR, 1.4 per log10 colony-forming units/mL increase; 95% CI, 1.0–1.8), older age (>50 years; OR, 3.9; 95% CI, 1.4–11.1), high peripheral white blood cell count (>10 × 109 cells/L; OR, 8.7; 95% CI, 2.5–30.2), fluconazole-based induction treatment, and slow clearance of CSF infection were independently associated with 2-week mortality. Low body weight, anemia (hemoglobin <7.5 g/dL), and low CSF opening pressure were independently associated with mortality at 10 weeks in addition to altered mental status, high fungal burden, high peripheral white cell count, and older age. In those followed for 1 year, overall mortality was 41%. Immune reconstitution inflammatory syndrome occurred in 13% of patients and was associated with 2-week CSF fungal burden (P = .007), but not with time to initiation of antiretroviral therapy (ART). Conclusions. CSF fungal burden, altered mental status, and rate of clearance of infection predict acute mortality in HIV-associated CM. The results suggest that earlier diagnosis, more rapidly fungicidal amphotericin-based regimens, and prompt immune reconstitution with ART are priorities for improving outcomes.

Methicillin-Resistant Staphylococcus aureus Therapy: Past, Present, and Future

Abstract: Methicillin-resistant Staphylococcus aureus (MRSA) continues to be associated with significant morbidity and mortality. Vancomycin was the "gold standard" of treatment for serious MRSA infections; however, the emergence of less-susceptible strains, poor clinical outcomes, and increased nephrotoxicity with high-dose therapy are challenging its current role as first-line therapy. Linezolid is recommended for PO or IV treatment of skin and skin structure infections (SSSIs) and pneumonia caused by MRSA. Daptomycin (IV) should be considered in patients with MRSA bacteremia and right-sided endocarditis as well as in complicated SSSIs, but should not be used to treat MRSA pneumonia. Tigecycline and telavancin are alternative (IV) treatments for SSSIs caused by MRSA; however, safety concerns have limited use of these agents. Ceftaroline is the newest of the approved parenteral agents for SSSIs caused by MRSA. Several investigational agents with activity against drug-resistant gram-positive pathogens are being developed primarily for treatment of MRSA infections, including tedizolid, dalbavancin, and oritavancin.

Clinical Practice Guideline for the Management of Chronic Kidney Disease in Patients Infected With HIV: 2014 Update by the HIV Medicine Association of the Infectious Diseases Society of America

Abstract: It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.

Shigella Isolates From the Global Enteric Multicenter Study Inform Vaccine Development

Abstract: Background Shigella, a major diarrheal disease pathogen worldwide, is the target of vaccine development. The Global Enteric Multicenter Study (GEMS) investigated burden and etiology of moderate-to-severe diarrheal disease in children aged Methods Subjects' stool specimens/rectal swabs were transported to site laboratories in transport media and plated onto xylose lysine desoxycholate and MacConkey agar. Suspect Shigella colonies were identified by biochemical tests and agglutination with antisera. Shigella isolates were shipped to the GEMS Reference Laboratory (Baltimore, MD) for confirmation and serotyping of S. flexneri; one-third of isolates were sent to the Centers for Disease Control and Prevention for quality control. Results Shigella dysenteriae and S. boydii accounted for 5.0% and 5.4%, respectively, of 1130 Shigella case isolates; S. flexneri comprised 65.9% and S. sonnei 23.7%. Five serotypes/subserotypes comprised 89.4% of S. flexneri, including S. flexneri 2a, S. flexneri 6, S. flexneri 3a, S. flexneri 2b, and S. flexneri 1b. Conclusions A broad-spectrum Shigella vaccine must protect against S. sonnei and 15 S. flexneri serotypes/subserotypes. A quadrivalent vaccine with O antigens from S. sonnei, S. flexneri 2a, S. flexneri 3a, and S. flexneri 6 can provide broad direct coverage against these most common serotypes and indirect coverage against all but 1 (rare) remaining subserotype through shared S. flexneri group antigens.

Impact of 13-Valent Pneumococcal Conjugate Vaccination in Invasive Pneumococcal Disease Incidence and Mortality

Abstract: BACKGROUND The impact of the 13-valent pneumococcal conjugate vaccine (PCV13) at the population level is unclear. We explored PCV13's effect in reducing invasive pneumococcal disease (IPD)-related morbidity and mortality, and whether serotype-specific changes were attributable to vaccination or expected as a part of natural, cyclical variations. METHODS This was a Danish nationwide population-based cohort study based on the linkage of laboratory surveillance data and the Danish Civil Registration System. Changes in IPD incidence and mortality during baseline (2000-2007), 7-valent pneumococcal conjugate vaccine (PCV7) (2008-2010), and PCV13 (2011-2013) periods were estimated. Predicted incidences of serotypes were estimated controlling for cyclical trends from historical patterns observed during the past 20 years. RESULTS We observed a 21% reduction (95% confidence interval [CI], 17%-25%) in IPD incidence in the total population after PCV13's introduction, and a 71% reduction (95% CI, 62%-79%) in children aged <2 years, considered as the vaccine effectiveness. We estimated a 28% reduction (95% CI, 18%-37%) in IPD-related 30-day mortality, from 3.4 deaths (95% CI, 3.2-3.6) per 100 000 population in the pre-PCV period to 2.4 (95% CI, 2.2-2.7) in the PCV13 period. The decline in mortality was observed across all age groups but was mainly related to mortality reductions in the nonvaccinated population. For serotypes 1 and 3, there were no significant changes in incidence beyond what would be expected from natural cyclical patterns. Serotype 19A significantly increased following PCV7's introduction, but the incidence declined toward baseline in 2012. CONCLUSIONS PCV13 has brought greater benefits than we had expected in our setting. We observed a further decline on IPD incidence shortly after the shift from PCV7 to PCV13 in the national immunization program. This decline was accompanied by a substantial population-level decline in pneumococcal-related mortality of nearly 30% among nonvaccinated persons.

Impact of Repeated Vaccination on Vaccine Effectiveness Against Influenza A(H3N2) and B During 8 Seasons

Abstract: Background. Recent studies suggest that influenza vaccination in the previous season may influence the effectiveness of current-season vaccination, but this has not been assessed in a single population over multiple years. Methods. Patients presenting with acute respiratory illness were prospectively enrolled during the 2004–2005 through 2012–2013 influenza seasons. Respiratory swabs were tested for influenza and vaccination dates obtained from a validated registry. Vaccination status was determined for the current, previous, and prior 5 seasons. Vaccine effectiveness (VE) was calculated for participants aged ≥9 years using logistic regression models with an interaction term for vaccination history. Results. There were 7315 enrollments during 8 seasons; 1056 (14%) and 650 (9%) were positive for influenza A(H3N2) and B, respectively. Vaccination during current only, previous only, or both seasons yielded similar protection against H3N2 (adjusted VE range, 31%–36%) and B (52%–66%). In the analysis using 5 years of historical vaccination data, current season VE against H3N2 was significantly higher among vaccinated individuals with no prior vaccination history (65%; 95% confidence interval [CI], 36%–80%) compared with vaccinated individuals with a frequent vaccination history (24%; 95% CI, 3%–41%; P = .01). VE against B was 75% (95% CI, 50%–87%) and 48% (95% CI, 29%–62%), respectively (P = .05). Similar findings were observed when analysis was restricted to adults 18–49 years. Conclusions. Current- and previous-season vaccination generated similar levels of protection, and vaccine-induced protection was greatest for individuals not vaccinated during the prior 5 years. Additional studies are needed to understand the long-term effects of annual vaccination.

The future of antibiotics and resistance: a tribute to a career of leadership by John Bartlett.

Abstract: The ways we have developed, used, and protected antibiotics have led, predictably, to our current crisis of rising antibiotic resistance and declining new treatments. If we want to stave off a postantibiotic era, we need to fundamentally change our approach. We need to challenge long-standing assumptions and cherished beliefs. We need to push through the reflexive resistance and excuses (eg, "that's not how we do things" and "that can't be done") that result from challenging established ways. Excuses abound. Action is needed. Ultimately, we need a coordinated national action plan to combat resistance. Herein we discuss 7 tasks and 3 common themes that cut across those tasks, which are necessary to achieve long-term success in dealing with antibiotics and resistance. These principles derive from many years of dialogue with Dr John Bartlett. The field of infectious diseases, and indeed medicine in general, has benefited immeasurably from his remarkable leadership.

Colistin and Polymyxin B: Peas in a Pod, or Chalk and Cheese?

Abstract: Colistin and polymyxin B have indistinguishable microbiological activity in vitro, but they differ in the form administered parenterally to patients. Polymyxin B is administered directly as the active antibiotic, whereas colistin is administered as the inactive prodrug, colistin methanesulfonate (CMS). CMS must be converted to colistin in vivo, but this occurs slowly and incompletely. Here we summarize the key differences between parenteral CMS/colistin and polymyxin B, and highlight the clinical implications. We put forth the view that overall polymyxin B has superior clinical pharmacological properties compared with CMS/colistin. We propose that in countries such as the United States where parenteral products of both colistin and polymyxin B are available, prospective studies should be conducted to formally examine their relative efficacy and safety in various types of infections and patients. In the meantime, where clinicians have access to both polymyxins, they should carefully consider the relative merits of each in a given circumstance.

Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents: Updated Guidelines From the Centers for Disease Control and Prevention, National Institutes of Health, and HIV Medicine Association of the Infectious Diseases Society of America

Abstract: In May 2013, a revised and updated version of the Centers for Disease Control and Prevention/National Institutes of Health/HIV Medicine Association Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents was released online. These guidelines, since their inception in 1989, have been widely accessed in the United States and abroad. These guidelines have focused on the management of HIV/AIDS-related opportunistic infections that occur in the United States. In other parts of the world, the spectrum of complications may be different and the resources available for diagnosis and management may not be identical to those in the United States. The sections that have been most extensively updated are those on immune reconstitution inflammatory syndrome, tuberculosis, hepatitis B, hepatitis C, human papillomavirus, and immunizations. The guidelines will not be published in hard copy form. This document will be revised as needed throughout each year as new data become available.

Healthcare-Associated Pneumonia Does Not Accurately Identify Potentially Resistant Pathogens: A Systematic Review and Meta-Analysis

Abstract: Background: The 2005 American Thoracic Society/Infectious Diseases Society of America guidelines introduced a concept of healthcare-associated pneumonia (HCAP) to define patients at higher risk of antibiotic-resistant pathogens, thus requiring broad spectrum therapy. There has been no systematic evaluation of the ability of this definition to identify antibiotic-resistant pathogens. Methods: We conducted a systematic review and meta-analysis of studies comparing the frequency of resistant pathogens (defined as methicillin-resistant Staphylococcus aureus, Enterobacteriaceae, and Pseudomonas aeruginosa) in populations with HCAP compared with populations with community-acquired pneumonia (CAP). Predictive accuracy was evaluated using the area under the receiver operator characteristic curve (AUC). The frequencies of pathogens in each group were pooled using a random effects model. Results: Twenty-four studies were included (n = 22 456). Overall study quality was poor. HCAP was associated with an increased risk of methicillin-resistant S. aureus (odds ratio [OR], 4.72; 95% confidence interval [CI], 3.69-6.04) enterobactericeae (OR, 2.11; 95% CI, 1.69-2.63), and P. aeruginosa (OR, 2.75; 95% CI, 2.04-3.72; all P < .0001), but these analyses were confounded by publication bias. The discriminatory ability of HCAP for resistant pathogens was low (AUC, 0.70; 95% CI, 0.69-0.71) and was lower in high-quality (AUC, 0.66; 95% CI, 0.62-0.70) and prospective studies (AUC, 0.64; 95% CI 0.62-0.66). After adjustment for age and comorbidities, mortality was not increased in HCAP (OR, 1.20; 95% CI, 0.85-1.70; P = .30). Conclusions: The HCAP concept is based on predominantly low-quality evidence and does not accurately identify resistant pathogens. Mortality in HCAP does not appear to be due to a higher frequency of resistant pathogens.