Agam K Rao

Outbreak of carbapenem-resistant enterobacteriaceae at a long-term acute care hospital: sustained reductions in transmission through active surveillance and targeted interventions.

OBJECTIVE To describe a Klebsiella pneumoniae carbapenemase (KPC)-producing carbapenem-resistant Enterobacteriaceae (CRE) outbreak and interventions to prevent transmission. DESIGN, SETTING, AND PATIENTS Epidemiologic investigation of a CRE outbreak among patients at a long-term acute care hospital (LTACH). METHODS Microbiology records at LTACH A from March 2009 through February 2011 were reviewed to identify CRE transmission cases and cases admitted with CRE. CRE bacteremia episodes were identified during March 2009-July 2011. Biweekly CRE prevalence surveys were conducted during July 2010-July 2011, and interventions to prevent transmission were implemented, including education and auditing of staff and isolation and cohorting of CRE patients with dedicated nursing staff and shared medical equipment. Trends were evaluated using weighted linear or Poisson regression. CRE transmission cases were included in a case-control study to evaluate risk factors for acquisition. A real-time polymerase chain reaction assay was used to detect the bla(KPC) gene, and pulsed-field gel electrophoresis was performed to assess the genetic relatedness of isolates. RESULTS Ninety-nine CRE transmission cases, 16 admission cases (from 7 acute care hospitals), and 29 CRE bacteremia episodes were identified. Significant reductions were observed in CRE prevalence (49% vs. 8%), percentage of patients screened with newly detected CRE (44% vs. 0%), and CRE bacteremia episodes (2.5 vs. 0.0 per 1,000 patient-days). Cases were more likely to have received β-lactams, have diabetes, and require mechanical ventilation. All tested isolates were KPC-producing K. pneumoniae, and nearly all isolates were genetically related. CONCLUSION CRE transmission can be reduced in LTACHs through surveillance testing and targeted interventions. Sustainable reductions within and across healthcare facilities may require a regional public health approach.

Cluster of Oseltamivir-Resistant 2009 Pandemic Influenza A (H1N1) Virus Infections on a Hospital Ward among Immunocompromised Patients—North Carolina, 2009

BACKGROUND Oseltamivir resistance among 2009 pandemic influenza A (H1N1) viruses (pH1N1) is rare. We investigated a cluster of oseltamivir-resistant pH1N1 infections in a hospital ward. METHODS We reviewed patient records and infection control measures and interviewed health care personnel (HCP) and visitors. Oseltamivir-resistant pH1N1 infections were found with real-time reverse-transcription polymerase chain reaction and pyrosequencing for the H275Y neuraminidase (NA) mutation. We compared hemagglutinin (HA) sequences from clinical samples from the outbreak with those of other surveillance viruses. RESULTS During the period 6-11 October 2009, 4 immunocompromised patients within a hematology-oncology ward exhibited symptoms of pH1N1 infection. The likely index patient became febrile 8 days after completing a course of oseltamivir; isolation was instituted 9 days after symptom onset. Three other case patients developed symptoms 1, 3, and 5 days after the index patient. Three case patients were located in adjacent rooms. HA and NA sequences from case patients were identical. Twelve HCP and 6 visitors reported influenza symptoms during the study period. No other pH1N1 isolates from the hospital or from throughout the state carried the H275Y mutation. CONCLUSIONS Geographic proximity, temporal clustering, presence of H275Y mutation, and viral sequence homology confirmed nosocomial transmission of oseltamivir-resistant pH1N1. Diagnostic vigilance and prompt isolation may prevent nosocomial transmission of influenza.

A Novel Botulinum Neurotoxin, Previously Reported as Serotype H, Has a Hybrid-Like Structure With Regions of Similarity to the Structures of Serotypes A and F and Is Neutralized With Serotype A Antitoxin

Botulism is a potentially fatal paralytic disease caused by the action of botulinum neurotoxin (BoNT) on nerve cells. There are 7 known serotypes (A-G) of BoNT and up to 40 genetic variants. Clostridium botulinum strain IBCA10-7060 was recently reported to produce BoNT serotype B (BoNT/B) and a novel BoNT, designated as BoNT/H. The BoNT gene (bont) sequence of BoNT/H was compared to known bont sequences. Genetic analysis suggested that BoNT/H has a hybrid-like structure containing regions of similarity to the structures of BoNT/A1 and BoNT/F5. This novel BoNT was serologically characterized by the mouse neutralization assay and a neuronal cell-based assay. The toxic effects of this hybrid-like BoNT were completely eliminated by existing serotype A antitoxins, including those contained in multivalent therapeutic antitoxin products that are the mainstay of human botulism treatment.

Efficacy of Antitoxin Therapy in Treating Patients With Foodborne Botulism: A Systematic Review and Meta-analysis of Cases, 1923–2016

Background Botulism is a rare, potentially severe illness, often fatal if not appropriately treated. Data on treatment are sparse. We systematically evaluated the literature on botulinum antitoxin and other treatments. Methods We conducted a systematic literature review of published articles in PubMed via Medline, Web of Science, Embase, Ovid, and Cumulative Index to Nursing and Allied Health Literature, and included all studies that reported on the clinical course and treatment for foodborne botulism. Articles were reviewed by 2 independent reviewers and independently abstracted for treatment type and toxin exposure. We conducted a meta-analysis on the effect of timing of antitoxin administration, antitoxin type, and toxin exposure type. Results We identified 235 articles that met the inclusion criteria, published between 1923 and 2016. Study quality was variable. Few (27%) case series reported sufficient data for inclusion in meta-analysis. Reduced mortality was associated with any antitoxin treatment (odds ratio [OR], 0.16; 95% confidence interval [CI], .09-.30) and antitoxin treatment within 48 hours of illness onset (OR, 0.12; 95% CI, .03-.41). Data did not allow assessment of critical care impact, including ventilator support, on survival. Therapeutic agents other than antitoxin offered no clear benefit. Patient characteristics did not predict poor outcomes. We did not identify an interval beyond which antitoxin was not beneficial. Conclusions Published studies on botulism treatment are relatively sparse and of low quality. Timely administration of antitoxin reduces mortality; despite appropriate treatment with antitoxin, some patients suffer respiratory failure. Prompt antitoxin administration and meticulous intensive care are essential for optimal outcome.

Safety and Improved Clinical Outcomes in Patients Treated With New Equine-Derived Heptavalent Botulinum Antitoxin

Background Botulism is a rare, life-threatening paralytic illness. Equine-derived heptavalent botulinum antitoxin (HBAT), the only currently available treatment for noninfant botulism in the United States, was licensed in 2013. No reports have systematically examined safety and clinical benefit of HBAT among botulism patients. Methods From March 2010 through March 2013, we collected data prospectively and through medical record reviews of patients with confirmed or suspected botulism who were treated with HBAT under an expanded-access Investigational New Drug program. Results Among 249 HBAT-treated patients, 1 (<1%) child experienced an HBAT-related serious adverse event (hemodynamic instability characterized by bradycardia, tachycardia, and asystole); 22 (9%) patients experienced 38 nonserious adverse events reported by physicians to be HBAT related. Twelve (5%) deaths occurred; all were determined to be likely unrelated to HBAT. Among 104 (42%) patients with confirmed botulism, those treated early (≤2 days) spent fewer days in the hospital (median, 15 vs 25 days; P < .01) and intensive care (10 vs 17 days; P = .04) than those treated later. Improvements in any botulism sign/symptom were detected a median of 2.4 days and in muscle strength a median of 4.8 days after HBAT. Conclusions HBAT was safe and provided clinical benefit in treated patients. HBAT administration within 2 days of symptom onset was associated with shorter hospital and intensive care stays. These results highlight the importance of maintaining clinical suspicion for botulism among patients presenting with paralytic illness to facilitate early HBAT treatment before laboratory confirmation might be available. Clinical consultation and, if indicated, HBAT release, are available to clinicians 24/7 through their state health department in conjunction with CDC.

Botulism During Pregnancy and the Postpartum Period: A Systematic Review

Background Maternal and fetal outcomes associated with botulism and botulinum antitoxin use during pregnancy and the postpartum period have not been systematically reviewed. Methods We searched Global Health, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Scopus, and Medline databases from inception to May 2015 for studies published on botulism or botulinum antitoxin use during pregnancy and the postpartum period, as well as the Centers for Disease Control and Prevention National Botulism Surveillance database. Our search identified 4517 citations. Results Sixteen cases of botulism during pregnancy (11 in the third trimester) and 1 case during the postpartum period were identified. Ten cases were associated with confirmed or likely foodborne exposure; 2 cases were attributed to wound contamination related to heroin use, and the source of 5 cases was unknown. Eleven women with botulism had progressive neurologic deterioration and respiratory failure, requiring intensive care unit admission. Four women had adverse outcomes, including 2 deaths and 2 women who remained in a persistent vegetative state. No neonatal losses or cases of congenital botulism were reported. Among the 12 cases that reported neonatal data, 6 neonates were born preterm. No adverse maternal or neonatal events were identified as associated with botulinum antitoxin therapy among 11 patients who received it. Conclusions Our review of 17 cases of botulism in pregnant/postpartum women found that more than half required ventilator support, 2 women died, and 6 infants were born prematurely. A high level of clinical suspicion is key for early diagnosis and treatment of botulism. Care of pregnant women or new mothers with botulism can include preparation for possible intubation.

A Qualitative Assessment of a Performance Measure for Reporting Influenza Vaccination Rates among Healthcare Personnel

To understand the feasibility of implementing a standardized performance measure for collecting and reporting influenza vaccination rates among healthcare personnel, qualitative, semistructured interviews were conducted with key informants in 32 healthcare facilities. Despite practical and logistical challenges to implementing the measure, respondents perceived clear benefits to its use.

A Qualitative Inquiry About Pruno, an Illicit Alcoholic Beverage Linked to Botulism Outbreaks in United States Prisons

OBJECTIVES Since 2011, 3 outbreaks of botulism in US prisons have been attributed to pruno, which is an alcoholic beverage made by inmates. Following 1 outbreak, we conducted a qualitative inquiry to understand pruno brewing and its social context to inform outbreak prevention measures. METHODS We interviewed staff, inmates, and parolees from 1 prison about pruno production methods, the social aspects of pruno, and strategies for communicating the association between botulism and pruno. RESULTS Twenty-seven inmates and parolees and 13 staff completed interviews. Pruno is fermented from water, fruit, sugar, and miscellaneous ingredients. Knowledge of pruno making was widespread among inmates; staff were familiar with only the most common ingredients and supplies inmates described. Staff and inmates described inconsistent consequences for pruno possession and suggested using graphic health messages from organizations external to the prison to communicate the risk of botulism from pruno. CONCLUSIONS Pruno making was frequent in this prison. Improved staff recognition of pruno ingredients and supplies might improve detection of brewing activities in this and other prisons. Consistent consequences and clear messages about the association between pruno and botulism might prevent outbreaks.

Outbreak of Foodborne Botulism in an Immigrant Community: Overcoming Delayed Disease Recognition, Ambiguous Epidemiologic Links, and Cultural Barriers to Identify the Cause

We describe a botulism outbreak involving 4 Middle Eastern men complicated by delayed diagnosis, ambiguous epidemiologic links among patients, and illness onset dates inconsistent with a point-source exposure. Homemade turshi, a fermented vegetable dish, was the likely cause. Patients ate turshi at 2 locations on different days over 1 month.

Outbreak of Botulism Due to Illicit Prison-Brewed Alcohol: Public Health Response to a Serious and Recurrent Problem

Background Botulism is a rare, sometimes lethal neuroparalytic illness. On 2 October 2011, an inmate at prison A developed symptoms compatible with botulism after drinking pruno, an illicit, prison-brewed alcoholic beverage. Additional illnesses were identified within several days. We conducted an investigation to determine the cause and extent of the outbreak. Methods A case was defined as signs or symptoms of botulism in a prison A inmate with onset during 30 September-9 October 2011. Cases were identified through medical evaluations and interviews with inmates about recent pruno consumption. Laboratory testing was performed for Clostridium botulinum and botulinum neurotoxin. Ingredients, preparation, and sharing of the implicated pruno were investigated. Results Eight prisoners developed botulism; all drank pruno made with a potato. Three received mechanical ventilation. Culture of fluid from a sock that inmates reported using to filter the implicated pruno yielded C. botulinum type A. The implicated batch may have been shared between cells during delivery of meal trays. Challenges of the investigation included identifying affected inmates, overcoming inaccuracies in histories, and determining how the illicit beverage was shared. Costs to taxpayers were nearly