Showing papers in "Clinical Infectious Diseases in 2016"
University of Alabama at Birmingham1, University of Michigan2, University of Wisconsin-Madison3, University of Pittsburgh4, Johns Hopkins University School of Medicine5, University of Texas Health Science Center at Houston6, Rowan University7, University of Pennsylvania8, Georgia Regents University9, Cornell University10, Boston Children's Hospital11, Wayne State University12
TL;DR: 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.
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.
2,367 citations
University of Nebraska Medical Center1, University of Connecticut2, Harvard University3, Queen's University4, University of California, San Diego5, Stony Brook University6, University of Michigan7, National Institutes of Health8, Johns Hopkins University9, University of Barcelona10, University at Buffalo11, Summa Health System12, University of Texas Health Science Center at San Antonio13, Royal Brisbane and Women's Hospital14, University of Queensland15, University of Western Australia16, University of Colorado Denver17, McMaster University18
TL;DR: These guidelines are intended for use by healthcare professionals who care for patients at risk for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), including specialists in infectious diseases, pulmonary diseases, critical care, and surgeons, anesthesiologists, hospitalists, and any clinicians and healthcare providers caring for hospitalized patients with nosocomial pneumonia.
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.These guidelines are intended for use by healthcare professionals who care for patients at risk for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), including specialists in infectious diseases, pulmonary diseases, critical care, and surgeons, anesthesiologists, hospitalists, and any clinicians and healthcare providers caring for hospitalized patients with nosocomial pneumonia. The panel's recommendations for the diagnosis and treatment of HAP and VAP are based upon evidence derived from topic-specific systematic literature reviews.
2,359 citations
Cornell University1, Boston University2, Johns Hopkins University3, University of Miami4, University of California, San Francisco5, Texas A&M Health Science Center College of Medicine6, Centers for Disease Control and Prevention7, University of Washington8, Case Western Reserve University9, University of Pennsylvania10, Denver Health Medical Center11, University of Michigan12, University of California, Davis13, University of California, Los Angeles14, United States Department of Veterans Affairs15, Washington University in St. Louis16, Wake Forest University17, University of Utah18, Memorial Sloan Kettering Cancer Center19
TL;DR: These recommendations address the best approaches for antibiotic stewardship programs to influence the optimal use of antibiotics.
Abstract: Evidence-based guidelines for implementation and measurement of antibiotic stewardship interventions in inpatient populations including long-term care were prepared by a multidisciplinary expert panel of the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. The panel included clinicians and investigators representing internal medicine, emergency medicine, microbiology, critical care, surgery, epidemiology, pharmacy, and adult and pediatric infectious diseases specialties. These recommendations address the best approaches for antibiotic stewardship programs to influence the optimal use of antibiotics.
1,969 citations
University of Texas Health Science Center at San Antonio1, University of California, Davis2, University Hospital of South Manchester NHS Foundation Trust3, Harvard University4, Tufts University5, University of Strasbourg6, University of Texas MD Anderson Cancer Center7, Johns Hopkins University8, University of Minnesota9, University of Pittsburgh10, Roswell Park Cancer Institute11, Duke University12, Cornell University13, University of Florida14, National Institutes of Health15
TL;DR: 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.
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.
1,745 citations
University of Alabama at Birmingham1, University of Michigan2, University of Wisconsin-Madison3, University of Pittsburgh4, Johns Hopkins University School of Medicine5, University of Texas Health Science Center at Houston6, Rowan University7, University of Pennsylvania8, Georgia Regents University9, Cornell University10, Boston Children's Hospital11, Wayne State University12
TL;DR: 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.
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.
1,124 citations
University of California, San Francisco1, Johns Hopkins University2, California Department of Public Health3, McMaster University4, World Health Organization5, Centers for Disease Control and Prevention6, Harvard University7, McGill University8, University of Washington9, University of Florida10, Boston University11, University of Cape Town12, University of Sassari13, Baylor College of Medicine14
TL;DR: This guideline provides recommendations on the clinical and public health management of tuberculosis in children and adults in settings in which mycobacterial cultures, molecular and phenotypic drug susceptibility tests, and radiographic studies, among other diagnostic tools, are available on a routine basis.
Abstract: The American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America jointly sponsored the development of this guideline for the treatment of drug-susceptible tuberculosis, which is also endorsed by the European Respiratory Society and the US National Tuberculosis Controllers Association. Representatives from the American Academy of Pediatrics, the Canadian Thoracic Society, the International Union Against Tuberculosis and Lung Disease, and the World Health Organization also participated in the development of the guideline. This guideline provides recommendations on the clinical and public health management of tuberculosis in children and adults in settings in which mycobacterial cultures, molecular and phenotypic drug susceptibility tests, and radiographic studies, among other diagnostic tools, are available on a routine basis. For all recommendations, literature reviews were performed, followed by discussion by an expert committee according to the Grading of Recommendations, Assessment, Development and Evaluation methodology. Given the public health implications of prompt diagnosis and effective management of tuberculosis, empiric multidrug treatment is initiated in almost all situations in which active tuberculosis is suspected. Additional characteristics such as presence of comorbidities, severity of disease, and response to treatment influence management decisions. Specific recommendations on the use of case management strategies (including directly observed therapy), regimen and dosing selection in adults and children (daily vs intermittent), treatment of tuberculosis in the presence of HIV infection (duration of tuberculosis treatment and timing of initiation of antiretroviral therapy), as well as treatment of extrapulmonary disease (central nervous system, pericardial among other sites) are provided. The development of more potent and better-tolerated drug regimens, optimization of drug exposure for the component drugs, optimal management of tuberculosis in special populations, identification of accurate biomarkers of treatment effect, and the assessment of new strategies for implementing regimens in the field remain key priority areas for research. See the full-text online version of the document for detailed discussion of the management of tuberculosis and recommendations for practice.
894 citations
TL;DR: While rotvirus vaccine had been introduced in >60 countries worldwide by the end of 2013, the majority of countries using rotavirus vaccine during the review period were low-mortality countries and the impact of rotav virus vaccine on global estimates of rotovirus mortality has been limited.
Abstract: Background Rotavirus vaccine is recommended for routine use in all countries globally. To facilitate decision making on rotavirus vaccine adoption by countries, help donors prioritize investments in health interventions, and monitor vaccine impact, we estimated rotavirus mortality for children Methods We searched PubMed using the keyword "rotavirus" to identify studies that met each of the following criteria: data collection midpoint in year 1998 or later, study period of a 12-month increment, and detection of rotavirus infection by enzyme immunoassay in at least 100 children Results Globally, we estimated that the number of rotavirus deaths in children Discussion While rotavirus vaccine had been introduced in >60 countries worldwide by the end of 2013, the majority of countries using rotavirus vaccine during the review period were low-mortality countries and the impact of rotavirus vaccine on global estimates of rotavirus mortality has been limited. Continued monitoring of rotavirus mortality rates and deaths through rotavirus surveillance will aid in monitoring the impact of vaccination.
827 citations
TL;DR: Azole resistance in Aspergillus fumigatus has now been reported from 6 continents and is emerging as a global health problem.
Abstract: Azole resistance in Aspergillus fumigatus has emerged as a global health problem. Although the number of cases of azole-resistant aspergillosis is still limited, resistance mechanisms continue to emerge, thereby threatening the role of the azole class in the management of diseases caused by Aspergillus. The majority of cases of azole-resistant disease are due to resistant A. fumigatus originating from the environment. Patient management is difficult due to the absence of patient risk factors, delayed diagnosis, and limited treatment options, resulting in poor treatment outcome. International and collaborative efforts are required to understand how resistance develops in the environment to allow effective measures to be implemented aimed at retaining the use of azoles both for food production and human medicine.
436 citations
TL;DR: Ceftolozane/tazobactam and ceftazidime/avibactam are 2 new second-generation cephalosporin/β-lactamase inhibitor combinations and may prove useful in the treatment of MDR GNB infections.
Abstract: Ceftolozane/tazobactam and ceftazidime/avibactam are 2 novel β-lactam/β-lactamase combination antibiotics. The antimicrobial spectrum of activity of these antibiotics includes multidrug-resistant (MDR) gram-negative bacteria (GNB), including Pseudomonas aeruginosa. Ceftazidime/avibactam is also active against carbapenem-resistant Enterobacteriaceae that produce Klebsiella pneumoniae carbapenemases. However, avibactam does not inactivate metallo-β-lactamases such as New Delhi metallo-β-lactamases. Both ceftolozane/tazobactam and ceftazidime/avibactam are only available as intravenous formulations and are dosed 3 times daily in patients with normal renal function. Clinical trials showed noninferiority to comparators of both agents when used in the treatment of complicated urinary tract infections and complicated intra-abdominal infections (when used with metronidazole). Results from pneumonia studies have not yet been reported. In summary, ceftolozane/tazobactam and ceftazidime/avibactam are 2 new second-generation cephalosporin/β-lactamase inhibitor combinations. After appropriate trials are conducted, they may prove useful in the treatment of MDR GNB infections. Antimicrobial stewardship will be essential to preserve the activity of these agents.
414 citations
Center for Excellence in Education1, University of Arizona2, Mayo Clinic3, University of California, San Diego4, Stanford University5, Sanford Health6, University of California, Los Angeles7, University of Utah8, Northwestern University9, Centers for Disease Control and Prevention10, St. Joseph's Hospital and Medical Center11
TL;DR: In this practice guideline, recommendations are organized to address actionable questions concerning the entire spectrum of clinical syndromes that can range from initial pulmonary infection, which eventually resolves whether or not antifungal therapy is administered, to a variety of pulmonary and extrapulmonary complications.
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. Infectious Diseases Society of America 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.Coccidioidomycosis, also known as San Joaquin Valley fever, is a systemic infection endemic to parts of the southwestern United States and elsewhere in the Western Hemisphere. Residence in and recent travel to these areas are critical elements for the accurate recognition of patients who develop this infection. In this practice guideline, we have organized our recommendations to address actionable questions concerning the entire spectrum of clinical syndromes. These can range from initial pulmonary infection, which eventually resolves whether or not antifungal therapy is administered, to a variety of pulmonary and extrapulmonary complications. Additional recommendations address management of coccidioidomycosis occurring for special at-risk populations. Finally, preemptive management strategies are outlined in certain at-risk populations and after unintentional laboratory exposure.
369 citations
TL;DR: Substantial reductions in HPV 6/11/16/18 infection, anogenital warts, and cervical lesions have been achieved.
Abstract: Prophylactic human papillomavirus (HPV) vaccination programs constitute major public health initiatives worldwide. We assessed the global effect of quadrivalent HPV (4vHPV) vaccination on HPV infection and disease. PubMed and Embase were systematically searched for peer-reviewed articles from January 2007 through February 2016 to identify observational studies reporting the impact or effectiveness of 4vHPV vaccination on infection, anogenital warts, and cervical cancer or precancerous lesions. Over the last decade, the impact of HPV vaccination in real-world settings has become increasingly evident, especially among girls vaccinated before HPV exposure in countries with high vaccine uptake. Maximal reductions of approximately 90% for HPV 6/11/16/18 infection, approximately 90% for genital warts, approximately 45% for low-grade cytological cervical abnormalities, and approximately 85% for high-grade histologically proven cervical abnormalities have been reported. The full public health potential of HPV vaccination is not yet realized. HPV-related disease remains a significant source of morbidity and mortality in developing and developed nations, underscoring the need for HPV vaccination programs with high population coverage.
TL;DR: Thirty-seven carbapenem-resistant Enterobacteriaceae-infected patients treated with ceftazidime-avibactam showed clinical success and survival rates and resistance was detected in 30% (3/10) of microbiologic failures.
Abstract: Thirty-seven carbapenem-resistant Enterobacteriaceae (CRE)-infected patients were treated with ceftazidime-avibactam. Clinical success and survival rates at 30 days were 59% (22/37) and 76% (28/37), respectively. In 23% (5/22) of clinical successes, CRE infections recurred within 90 days. Microbiologic failure rate was 27% (10/37). Ceftazidime-avibactam resistance was detected in 30% (3/10) of microbiologic failures.
TL;DR: The ESBL colonization rate among healthy individuals is significant worldwide and should be taken into consideration in infection control and antibiotic management decisions.
Abstract: Background Gut colonization is a risk factor for infections with extended-spectrum beta-lactamase (ESBL)-producing organisms. We aimed to determine the ESBL class A reservoir among healthy individuals. Methods We searched PubMed and EMBASE (through 10 July 2015) looking for studies that contained data for fecal colonization with ESBL class A bacteria among healthy individuals for each World Health Organization-defined region. Distribution of isolates among cefotaximase (CTX-M), sulfhydryl variable, and temoneira enzymes and data on previous antibiotic use, international travel, previous hospitalization, and animal contacts were extracted. Results Sixty-six of 17 479 studies on 28 909 healthy individuals were included. The pooled prevalence of ESBL class A colonization was 14% (95% confidence interval [CI], 9, 20), with an increasing trend of 5.38% annually (P = .003). The pooled prevalence was higher in Asia and Africa (ranging from 46%, 95% CI, 29, 63 to 15%, 95% CI, 4, 31) and lower but still significant in central (3%, 95% CI, 1, 5), northern (4%, 95% CI, 2, 6), and southern Europe (6%, 95% CI, 1, 12) and the Americas (2%, 95% CI, 0, 5). CTX-Ms were the prevalent ESBL enzyme (69%). Antibiotic use for the prior 4 or 12 months was associated with a high colonization risk (risk ratio [RR] = 1.63; 95% CI, 1.19, 2.24 and RR = 1.58; 95% CI, 1.16, 2.16, respectively). International travel was also correlated with ESBL colonization [(RR = 4.06, (95% CI, 1.33, 12.41)]. Conclusions The ESBL colonization rate among healthy individuals is significant worldwide. This should be taken into consideration in infection control and antibiotic management decisions.
Boston University1, Johns Hopkins University2, University of Miami3, University of California, San Francisco4, Cornell University5, Texas A&M Health Science Center College of Medicine6, Centers for Disease Control and Prevention7, University of Washington8, Case Western Reserve University9, University of Pennsylvania10, Denver Health Medical Center11, University of Michigan12, University of California, Davis13, University of California, Los Angeles14, United States Department of Veterans Affairs15, Washington University in St. Louis16, Wake Forest University17, University of Utah18, Memorial Sloan Kettering Cancer Center19
TL;DR: These recommendations address the best approaches for antibiotic stewardship programs to influence the optimal use of antibiotics.
Abstract: Evidence-based guidelines for implementation and measurement of antibiotic stewardship interventions in inpatient populations including long-term care were prepared by a multidisciplinary expert panel of the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. The panel included clinicians and investigators representing internal medicine, emergency medicine, microbiology, critical care, surgery, epidemiology, pharmacy, and adult and pediatric infectious diseases specialties. These recommendations address the best approaches for antibiotic stewardship programs to influence the optimal use of antibiotics.
TL;DR: In the United States, hepatitis C virus (HCV)-associated mortality is increasing, and from 2003-2013, the number of deaths associated with HCV has now surpassed 60 other nationally notifiable infectious conditions combined.
Abstract: In the United States, hepatitis C virus (HCV)-associated mor- tality is increasing. From 2003-2013, the number of deaths as- sociated with HCV has now surpassed 60 other nationally notifiable infectious conditions combined. The increasing HCV-associated mortality trend underscores the urgency in finding, evaluating, and treating HCV-infected persons. Keywords. hepatitis C; mortality trends; death certificates; causes of death. Despite enthusiasm for the new curative, brief (12-week), all- oral antiviral treatments for hepatitis C virus (HCV) infection, the continued health burden (1)and increased mortality (2) for HCV-infected patients in the United States remain underappre- ciated. We examined national multiple-cause-of-death (MCOD) data from 2003 to 2013 to provide more current estimates of trends in hepatitis C-related mortality in the United States and compared these with trends in deaths associated with 60 other nationally notifiable infectious conditions (ONNICs) that are routinelyreported totheCentersfor Disease Controland Preven- tion (CDC). METHODS Death certificate information from the public-use MCOD data, obtained from the National Center for Health Statistics, was ex- amined. Mortality codes for 2 disease categories, hepatitis C and ONNICs, as classified by the International Classification of Dis- eases, 10th Revision (ICD-10 )( 3), were examined. Deaths asso- ciated with hepatitis C were defined as having the ICD-10 codes B17.1 and B18.2 listed in the "record axis" MCOD fields. Deaths associated with ONNICs (4) were defined as having any of the ICD-10 codes associated with 60 conditions (see Supplementary Appendix) recorded in the "record axis" MCOD fields. To en- sure mutual exclusivity between the 2 disease categories, any ONNIC-related death that also had a listing of hepatitis C
TL;DR: In this randomized phase 3 trial, ceftazidime-avibactam plus metronidazole was noninferior to meropenem in treating complicated intra-abdominal infection and with similar efficacy against ceftazerime-resistant and ceftZidime -resistant pathogens and no new safety concerns observed.
Abstract: Background When combined with ceftazidime, the novel non-β-lactam β-lactamase inhibitor avibactam provides a carbapenem alternative against multidrug-resistant infections. Efficacy and safety of ceftazidime-avibactam plus metronidazole were compared with meropenem in 1066 men and women with complicated intra-abdominal infections from 2 identical, randomized, double-blind phase 3 studies (NCT01499290 and NCT01500239). Methods The primary end point was clinical cure at test-of-cure visit 28-35 days after randomization, assessed by noninferiority of ceftazidime-avibactam plus metronidazole to meropenem in the microbiologically modified intention-to-treat (mMITT) population (in accordance with US Food and Drug Administration guidance), and the modified intention-to-treat and clinically evaluable populations (European Medicines Agency guidance). Noninferiority was considered met if the lower limit of the 95% confidence interval for between-group difference was greater than the prespecified noninferiority margin of -12.5%. Results Ceftazidime-avibactam plus metronidazole was noninferior to meropenem across all primary analysis populations. Clinical cure rates with ceftazidime-avibactam plus metronidazole and meropenem, respectively, were as follows: mMITT population, 81.6% and 85.1% (between-group difference, -3.5%; 95% confidence interval -8.64 to 1.58); modified intention-to-treat, 82.5% and 84.9% (-2.4%; -6.90 to 2.10); and clinically evaluable, 91.7% and 92.5% (-0.8%; -4.61 to 2.89). The clinical cure rate with ceftazidime-avibactam plus metronidazole for ceftazidime-resistant infections was comparable to that with meropenem (mMITT population, 83.0% and 85.9%, respectively) and similar to the regimen's own efficacy against ceftazidime-susceptible infections (82.0%). Adverse events were similar between groups. Conclusions Ceftazidime-avibactam plus metronidazole was noninferior to meropenem in the treatment of complicated intra-abdominal infections. Efficacy was similar against infections caused by ceftazidime-susceptible and ceftazidime-resistant pathogens. The safety profile of ceftazidime-avibactam plus metronidazole was consistent with that previously observed with ceftazidime alone. Clinical trials registration NCT01499290 and NCT01500239.
TL;DR: This is the first time a comprehensive, multipathogen, quantitative and qualitative molecular approach for respiratory bacteria and viruses has been compared with traditional diagnostic methods on a large hospitalized pneumonia cohort, with estimation of potential effects on antibiotic prescribing.
Abstract: Background. The frequent lack of a microbiological diagnosis in community-acquired pneumonia (CAP) impairs pathogen-directed antimicrobial therapy. This study assessed the use of comprehensive multibacterial, multiviral molecular testing, including quantification, in adults hospitalized with CAP.
Methods. Clinical and laboratory data were collected for 323 adults with radiologically-confirmed CAP admitted to 2 UK tertiary care hospitals. Sputum (96%) or endotracheal aspirate (4%) specimens were cultured as per routine practice and also tested with fast multiplex real-time polymerase-chain reaction (PCR) assays for 26 respiratory bacteria and viruses. Bacterial loads were also calculated for 8 bacterial pathogens. Appropriate pathogen-directed therapy was retrospectively assessed using national guidelines adapted for local antimicrobial susceptibility patterns.
Results. Comprehensive molecular testing of single lower respiratory tract (LRT) specimens achieved pathogen detection in 87% of CAP patients compared with 39% with culture-based methods. Haemophilus influenzae and Streptococcus pneumoniae were the main agents detected, along with a wide variety of typical and atypical pathogens. Viruses were present in 30% of cases; 82% of these were codetections with bacteria. Most (85%) patients had received antimicrobials in the 72 hours before admission. Of these, 78% had a bacterial pathogen detected by PCR but only 32% were culture-positive (P < .0001). Molecular testing had the potential to enable de-escalation in number and/or spectrum of antimicrobials in 77% of patients.
Conclusions. Comprehensive molecular testing significantly improves pathogen detection in CAP, particularly in antimicrobial-exposed patients, and requires only a single LRT specimen. It also has the potential to enable early de-escalation from broad-spectrum empirical antimicrobials to pathogen-directed therapy.
TL;DR: Whole-genome multilocus sequence typing and single nucleotide polymorphism analyses provided equivalent phylogenetic relationships relevant to investigations; results were most useful when interpreted in context of epidemiological data.
Abstract: Listeria monocytogenes (Lm) causes severe foodborne illness (listeriosis). Previous molecular subtyping methods, such as pulsed-field gel electrophoresis (PFGE), were critical in detecting outbreaks that led to food safety improvements and declining incidence, but PFGE provides limited genetic resolution. A multiagency collaboration began performing real-time, whole-genome sequencing (WGS) on all US Lm isolates from patients, food, and the environment in September 2013, posting sequencing data into a public repository. Compared with the year before the project began, WGS, combined with epidemiologic and product trace-back data, detected more listeriosis clusters and solved more outbreaks (2 outbreaks in pre-WGS year, 5 in WGS year 1, and 9 in year 2). Whole-genome multilocus sequence typing and single nucleotide polymorphism analyses provided equivalent phylogenetic relationships relevant to investigations; results were most useful when interpreted in context of epidemiological data. WGS has transformed listeriosis outbreak surveillance and is being implemented for other foodborne pathogens.
Uniformed Services University of the Health Sciences1, Centers for Disease Control and Prevention2, McGill University Health Centre3, University of Virginia4, University of Alcalá5, Walter Reed National Military Medical Center6, Oswaldo Cruz Foundation7, Federal University of Rio Grande do Norte8, Bill & Melinda Gates Foundation9
TL;DR: It is important to realize that leishmaniasis guidelines cannot always account for individual variation among patients, and that adherence to these guidelines to be voluntary.
Abstract: It is important to realize that leishmaniasis 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. The IDSA and ASTMH consider adherence to these guidelines to be voluntary, with the ultimate determinations regarding their application to be made by the physician in the light of each patient's individual circumstances.
TL;DR: Ceftazidime-avibactam was highly effective for empiric treatment of complicated urinary tract infection, including in patients with ceftazodime-nonsusceptible pathogens, and may offer an alternative to carbapenems in this setting.
Abstract: Background. The global emergence of carbapenem-resistant Enterobacteriaceae highlights the urgent need to reduce carbapenem dependence. The phase 3 RECAPTURE program compared the efficacy and safety of ceftazidime-avibactam and doripenem in patients with complicated urinary tract infection (cUTI), including acute pyelonephritis.
Methods. Hospitalized adults with suspected or microbiologically confirmed cUTI/acute pyelonephritis were randomized 1:1 to ceftazidime-avibactam 2000 mg/500 mg every 8 hours or doripenem 500 mg every 8 hours (doses adjusted for renal function), with possible oral antibiotic switch after ≥5 days (total treatment duration up to 10 days or 14 days for patients with bacteremia).
Results. Of 1033 randomized patients, 393 and 417 treated with ceftazidime-avibactam and doripenem, respectively, were eligible for the primary efficacy analyses; 19.6% had ceftazidime-nonsusceptible baseline pathogens. Noninferiority of ceftazidime-avibactam vs doripenem was demonstrated for the US Food and Drug Administration co-primary endpoints of (1) patient-reported symptomatic resolution at day 5: 276 of 393 (70.2%) vs 276 of 417 (66.2%) patients (difference, 4.0% [95% confidence interval {CI}, −2.39% to 10.42%]); and (2) combined symptomatic resolution/microbiological eradication at test of cure (TOC): 280 of 393 (71.2%) vs 269 of 417 (64.5%) patients (difference, 6.7% [95% CI, .30% to 13.12%]). Microbiological eradication at TOC (European Medicines Agency primary endpoint) occurred in 304 of 393 (77.4%) ceftazidime-avibactam vs 296 of 417 (71.0%) doripenem patients (difference, 6.4% [95% CI, .33% to 12.36%]), demonstrating superiority at the 5% significance level. Both treatments showed similar efficacy against ceftazidime-nonsusceptible pathogens. Ceftazidime-avibactam had a safety profile consistent with that of ceftazidime alone.
Conclusions. Ceftazidime-avibactam was highly effective for the empiric treatment of cUTI (including acute pyelonephritis), and may offer an alternative to carbapenems in this setting.
Clinical Trials Registration. {"type":"clinical-trial","attrs":{"text":"NCT01595438","term_id":"NCT01595438"}}NCT01595438; {"type":"clinical-trial","attrs":{"text":"NCT01599806","term_id":"NCT01599806"}}NCT01599806.
Vanderbilt University1, National Center for Immunization and Respiratory Diseases2, Emory University3, Colorado Department of Public Health and Environment4, New York State Department of Health5, California Department of Public Health6, Oregon Health Authority7, University of New Mexico8, Johns Hopkins University9
TL;DR: The burden of invasive GAS infection in the United States remains substantial and vaccines under development could have a considerable public health impact.
Abstract: BACKGROUND Invasive group A Streptococcus (GAS) infections are associated with significant morbidity and mortality rates. We report the epidemiology and trends of invasive GAS over 8 years of surveillance. METHODS From January 2005 through December 2012, we collected data from the Centers for Disease Control and Prevention's Active Bacterial Core surveillance, a population-based network of 10 geographically diverse US sites (2012 population, 32.8 million). We defined invasive GAS as isolation of GAS from a normally sterile site or from a wound in a patient with necrotizing fasciitis (NF) or streptococcal toxic shock syndrome (STSS). Available isolates were emm typed. We calculated rates and made age- and race-adjusted national projections using census data. RESULTS We identified 9557 cases (3.8 cases per 100 000 persons per year) with 1116 deaths (case-fatality rate, 11.7%). The case-fatality rates for septic shock, STSS, and NF were 45%, 38%, and 29%, respectively. The annual incidence was highest among persons aged ≥65 years (9.4/100 000) or <1 year (5.3) and among blacks (4.7/100 000). National rates remained steady over 8 years of surveillance. Factors independently associated with death included increasing age, residence in a nursing home, recent surgery, septic shock, NF, meningitis, isolated bacteremia, pneumonia, emm type 1 or 3, and underlying chronic illness or immunosuppression. An estimated 10 649-13 434 cases of invasive GAS infections occur in the United States annually, resulting in 1136-1607 deaths. In a 30-valent M-protein vaccine, emm types accounted for 91% of isolates. CONCLUSIONS The burden of invasive GAS infection in the United States remains substantial. Vaccines under development could have a considerable public health impact.
TL;DR: Zika virus, chikungunya virus, and dengue virus result in similar clinical presentations, and coinfections may be relatively common.
Abstract: Background. Zika virus (ZIKV), chikungunya virus (CHIKV), and dengue virus (DENV) cocirculate in Nicaragua. In this study, we sought to compare the quantified viremia and clinical presentation of patients infected with 1 or more of these viruses.
Methods. Acute-phase serum samples from 346 patients with a suspected arboviral illness were tested using a multiplex real-time reverse-transcription polymerase chain reaction for ZIKV, CHIKV, and DENV. Viremia was quantitated for each detected virus, and clinical information from request forms submitted with each sample was recorded.
Results. A total of 263 patients tested positive for 1 or more viruses: 192 patients tested positive for a single virus (monoinfections) and 71 patients tested positive for 2 or all 3 viruses (coinfections). Quantifiable viremia was lower in ZIKV infections compared with CHIKV or DENV (mean 4.70 vs 6.42 and 5.84 log10 copies/mL serum, respectively; P < .001 for both comparisons), and for each virus, mean viremia was significantly lower in coinfections than in monoinfections. Compared with patients with CHIKV or DENV, ZIKV patients were more likely to have a rash (P < .001) and less likely to be febrile (P < .05) or require hospitalization (P < .001). Among all patients, hospitalized cases had higher viremia than those who did not require hospitalization (7.1 vs 4.1 log10 copies/mL serum, respectively; P < .001).
Conclusions. ZIKV, CHIKV, and DENV result in similar clinical presentations, and coinfections may be relatively common. Our findings illustrate the need for accurate, multiplex diagnostics for patient care and epidemiologic surveillance.
University of Texas Health Science Center at San Antonio1, University of California, Davis2, University Hospital of South Manchester NHS Foundation Trust3, Harvard University4, Tufts University5, University of Strasbourg6, University of Texas MD Anderson Cancer Center7, Johns Hopkins University8, University of Minnesota9, University of Pittsburgh10, Roswell Park Cancer Institute11, Duke University12, Cornell University13, University of Florida14, National Institutes of Health15
TL;DR: 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.
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.
TL;DR: The evidence supports the notion that risk of recurrence is driven by reinfection, and sustained virological response is durable in patients treated for hepatitis C virus.
Abstract: Infection with the hepatitis C virus (HCV) is a significant public health concern associated with a high burden of morbidity and mortality [1, 2]. Recent estimates suggest that worldwide, of the 185 million individuals infected, over 700 000 people die annually as a result of infection [3, 4].
The attainment of a sustained virological response (SVR), defined as aviremia 12 or 24 weeks after the completion of antiviral therapy (SVR12 or SVR24), is associated with an improved prognosis compared with patients either untreated or failing therapy. These benefits include improved histology, reduced risk of hepatocellular carcinoma, and improved overall survival [5, 6].
Despite these benefits, treatment uptake for chronic HCV has been low due to complexities of treatment and poor success rates. The availability of new highly efficacious regimens provides the foundation for marked treatment scale-up; however, high costs are currently limiting access [7–10].
One challenge to treatment scale-up is the risk of HCV recurrence, either as late relapse post-SVR or reinfection following treatment. HCV recurrence is a particular concern in patients with ongoing high-risk behaviors, such as injecting drug users (IDUs), who are more susceptible to reinfection, and also patients coinfected with human immunodeficiency virus (HIV) who may be at increased risk of relapse due to their immunocompromised status [11–15].
A number of studies have been carried out to examine the durability of treatment-induced SVR in patients with chronic HCV in a variety of patient populations. Our aim was to systematically review the existing evidence and undertake meta-analysis to provide summary estimates of the recurrence rate by risk group. The secondary aim was to evaluate the contribution of late relapse and of reinfection to the recurrence rate. This work fits within the theme one of the PROGRESS framework for prognosis research (“fundamental prognosis research”) and will provide a clearer understanding of HCV recurrence to inform the provision of antiviral therapy [16].
TL;DR: The 2014-2015 influenza vaccines offered little protection against the predominant influenza A/H3N2 virus but were effective against influenza B and preferential use of LAIV among young children was not supported.
Abstract: Background Circulating A/H3N2 influenza viruses drifted significantly after strain selection for the 2014-2015 vaccines. Also in 2014-2015, the Advisory Committee on Immunization Practices recommended preferential use of live attenuated influenza vaccine (LAIV) over inactivated influenza vaccine (IIV) among children aged 2-8 years. Methods Vaccine effectiveness (VE) across age groups and vaccine types was examined among outpatients with acute respiratory illness at 5 US sites using a test-negative design, that compared the odds of vaccination among reverse transcription polymerase chain reaction-confirmed influenza positives and negatives. Results Of 9311 enrollees with complete data, 7078 (76%) were influenza negative, 1840 (19.8%) were positive for influenza A (A/H3N2, n = 1817), and 395 (4.2%) were positive for influenza B (B/Yamagata, n = 340). The overall adjusted VE was 19% (95% confidence interval [CI], 10% to 27%) and was statistically significant in all age strata except those aged 18-64 years. The adjusted VE of 6% (95%CI, -5% to 17%) against A/H3N2-associated illness was not statistically significant, unlike VE for influenza B/Yamagata, which was 55% (95%CI, 43% to 65%). Among those aged 2-8 years, VE against A/H3N2 was 15% (95%CI, -16% to 38%) for IIV and -3% (CI, -50% to 29%) for LAIV; VE against B/Yamagata was 40% (95%CI, -20% to 70%) for IIV and 74% (95%CI, 25% to 91%) for LAIV. Conclusions The 2014-2015 influenza vaccines offered little protection against the predominant influenza A/H3N2 virus but were effective against influenza B. Preferential use of LAIV among young children was not supported.
TL;DR: It is shown that this narrow window for vaccinated women against pertussis can be widened, as optimal neonatal antibody concentrations and expected infant seropositivity rates are elicited between weeks 13 and 33.
Abstract: Background. Maternal immunization against pertussis is currently recommended after the 26th gestational week (GW). Data on the optimal timing of maternal immunization are inconsistent.
Methods. We conducted a prospective observational noninferiority study comparing the influence of second-trimester (GW 13–25) vs third-trimester (≥GW 26) tetanus-diphtheria-acellular pertussis (Tdap) immunization in pregnant women who delivered at term. Geometric mean concentrations (GMCs) of cord blood antibodies to recombinant pertussis toxin (PT) and filamentous hemagglutinin (FHA) were assessed by enzyme-linked immunosorbent assay. The primary endpoint were GMCs and expected infant seropositivity rates, defined by birth anti-PT >30 enzyme-linked immunosorbent assay units (EU)/mL to confer seropositivity until 3 months of age.
Results. We included 335 women (mean age, 31.0 ± 5.1 years; mean gestational age, 39.3 ± 1.3 GW) previously immunized with Tdap in the second (n = 122) or third (n = 213) trimester. Anti-PT and anti-FHA GMCs were higher following second- vs third-trimester immunization (PT: 57.1 EU/mL [95% confidence interval {CI}, 47.8–68.2] vs 31.1 EU/mL [95% CI, 25.7–37.7], P < .001; FHA: 284.4 EU/mL [95% CI, 241.3–335.2] vs 140.2 EU/mL [95% CI, 115.3–170.3], P < .001). The adjusted GMC ratios after second- vs third-trimester immunization differed significantly (PT: 1.9 [95% CI, 1.4–2.5]; FHA: 2.2 [95% CI, 1.7–3.0], P < .001). Expected infant seropositivity rates reached 80% vs 55% following second- vs third-trimester immunization (adjusted odds ratio, 3.7 [95% CI, 2.1–6.5], P < .001).
Conclusions. Early second-trimester maternal Tdap immunization significantly increased neonatal antibodies. Recommending immunization from the second trimester onward would widen the immunization opportunity window and could improve seroprotection.
TL;DR: The risk of infection among patients receiving immune checkpoint blockade is unknown, and the main risk factors were receipt of corticosteroids and/or infliximab.
Abstract: The risk of infection among patients receiving immune checkpoint blockade is unknown. We retrospectively reviewed medical records of 740 patients with melanoma who received immune checkpoint blockers. Serious infection occurred in 54 patients (7.3%). The main risk factors were receipt of corticosteroids and/or infliximab.
TL;DR: There is no evidence of increased risk of disease after primary immunization in infants whose mothers received maternal vaccination and there is no longer evidence of additional protection from maternal vaccination after the third infant dose.
Abstract: The effectiveness of maternal immunization in preventing infant pertussis was first demonstrated in England, 1 year after the program using diphtheria-tetanus-5-component acellular pertussis-inactivated polio vaccine (dT5aP-IPV) was introduced in 2012. Vaccine effectiveness against laboratory-confirmed pertussis has been sustained >90% in the 3 years following its introduction, despite changing to another acellular vaccine with different antigen composition. Consistent with this, disease incidence in infants <3 months of age has remained low despite high activity persisting in those aged 1 year and older. Vaccine effectiveness against infant deaths was estimated at 95% (95% confidence interval, 79%-100%). Additional protection from maternal immunization is retained in infants who received their first dose of the primary series. There is no longer evidence of additional protection from maternal vaccination after the third infant dose. Although numbers are small and ongoing assessment is required, there is no evidence of increased risk of disease after primary immunization in infants whose mothers received maternal vaccination.
TL;DR: Middle East respiratory syndrome (MERS) coronavirus was found by reverse-transcription polymerase-chain-reaction from viral cultures of 4 of 7 air samples and 15 of 68 surface swabs from 3 MERS patients' rooms, calling for epidemiologic investigation for contact and airborne transmission.
Abstract: Background. The largest outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) outside the Middle East occurred in South Korea in 2015 and resulted in 186 laboratory-confirmed infections, including 36 (19%) deaths. Some hospitals were considered epicenters of infection and voluntarily shut down most of their operations after nearly half of all transmissions occurred in hospital settings. However, the ways that MERS-CoV is transmitted in healthcare settings are not well defined.
Methods. We explored the possible contribution of contaminated hospital air and surfaces to MERS transmission by collecting air and swabbing environmental surfaces in 2 hospitals treating MERS-CoV patients. The samples were tested by viral culture with reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence assay (IFA) using MERS-CoV Spike antibody, and electron microscopy (EM).
Results. The presence of MERS-CoV was confirmed by RT-PCR of viral cultures of 4 of 7 air samples from 2 patients' rooms, 1 patient's restroom, and 1 common corridor. In addition, MERS-CoV was detected in 15 of 68 surface swabs by viral cultures. IFA on the cultures of the air and swab samples revealed the presence of MERS-CoV. EM images also revealed intact particles of MERS-CoV in viral cultures of the air and swab samples.
Conclusions. These data provide experimental evidence for extensive viable MERS-CoV contamination of the air and surrounding materials in MERS outbreak units. Thus, our findings call for epidemiologic investigation of the possible scenarios for contact and airborne transmission, and raise concern regarding the adequacy of current infection control procedures.
TL;DR: The current large-scale use of fluoroquinolones, macrolides, and third-generation cephalosporins and any potential use of glycopeptides and carbapenems need to be addressed urgently.
Abstract: Antimicrobial use in food animals selects for antimicrobial resistance in bacteria, which can spread to people. Reducing use of antimicrobials-particularly those deemed to be critically important for human medicine-in food production animals continues to be an important step for preserving the benefits of these antimicrobials for people. The World Health Organization ranking of antimicrobials according to their relative importance in human medicine was recently updated. Antimicrobials considered the highest priority among the critically important antimicrobials were quinolones, third- and fourth-generation cephalosporins, macrolides and ketolides, and glycopeptides. The updated ranking allows stakeholders in the agriculture sector and regulatory agencies to focus risk management efforts on drugs used in food animals that are the most important to human medicine. In particular, the current large-scale use of fluoroquinolones, macrolides, and third-generation cephalosporins and any potential use of glycopeptides and carbapenems need to be addressed urgently.