Amee Patrawalla

Planning against Biological Terrorism: Lessons from Outbreak Investigations

We examined outbreak investigations conducted around the world from 1988 to 1999 by the Centers for Disease Control and Prevention’s Epidemic Intelligence Service. In 44 (4.0%) of 1,099 investigations, identified causative agents had bioterrorism potential. In six investigations, intentional use of infectious agents was considered. Healthcare providers reported 270 (24.6%) outbreaks and infection control practitioners reported 129 (11.7%); together they reported 399 (36.3%) of the outbreaks. Health departments reported 335 (30.5%) outbreaks. For six outbreaks in which bioterrorism or intentional contamination was possible, reporting was delayed for up to 26 days. We confirmed that the most critical component for bioterrorism outbreak detection and reporting is the frontline healthcare profession and the local health departments. Bioterrorism preparedness should emphasize education and support of this frontline as well as methods to shorten the time between outbreak and reporting.

Colistin- and Carbapenem-Resistant Escherichia coli Harboring mcr-1 and blaNDM-5, Causing a Complicated Urinary Tract Infection in a Patient from the United States

ABSTRACT Colistin is increasingly used as an antibiotic of last resort for the treatment of carbapenem-resistant Gram-negative infections. The plasmid-borne colistin resistance gene mcr-1 was initially identified in animal and clinical samples from China and subsequently reported worldwide, including in the United States. Of particular concern is the spread of mcr-1 into carbapenem-resistant bacteria, thereby creating strains that approach pan-resistance. While several reports of mcr-1 have involved carbapenem-resistant strains, no such isolates have been described in the United States. Here, we report the isolation and identification of an Escherichia coli strain harboring both mcr-1 and carbapenemase gene blaNDM-5 from a urine sample in a patient without recent travel outside the United States. The isolate exhibited resistance to both colistin and carbapenems, but was susceptible to amikacin, aztreonam, gentamicin, nitrofurantoin, tigecycline, and trimethoprim-sulfamethoxazole. The mcr-1- and blaNDM-5-harboring plasmids were completely sequenced and shown to be highly similar to plasmids previously reported from China. The strain in this report was first isolated in August 2014, highlighting an earlier presence of mcr-1 within the United States than previously recognized. IMPORTANCE Colistin has become the last line of defense for the treatment of infections caused by Gram-negative bacteria resistant to multiple classes of antibiotics, in particular carbapenem-resistant Enterobacteriaceae (CRE). Resistance to colistin, encoded by the plasmid-borne gene mcr-1, was first identified in animal and clinical samples from China in November 2015 and has subsequently been reported from numerous other countries. In April 2016, mcr-1 was identified in a carbapenem-susceptible Escherichia coli strain from a clinical sample in the United States, followed by a second report from a carbapenem-susceptible E. coli strain originally isolated in May 2015. We report the isolation and identification of an E. coli strain harboring both colistin (mcr-1) and carbapenem (blaNDM-5) resistance genes, originally isolated in August 2014 from urine of a patient with recurrent urinary tract infections. To our knowledge, this is the first report in the United States of a clinical bacterial isolate with both colistin and carbapenem resistance, highlighting the importance of active surveillance efforts for colistin- and carbapenem-resistant organisms. Colistin has become the last line of defense for the treatment of infections caused by Gram-negative bacteria resistant to multiple classes of antibiotics, in particular carbapenem-resistant Enterobacteriaceae (CRE). Resistance to colistin, encoded by the plasmid-borne gene mcr-1, was first identified in animal and clinical samples from China in November 2015 and has subsequently been reported from numerous other countries. In April 2016, mcr-1 was identified in a carbapenem-susceptible Escherichia coli strain from a clinical sample in the United States, followed by a second report from a carbapenem-susceptible E. coli strain originally isolated in May 2015. We report the isolation and identification of an E. coli strain harboring both colistin (mcr-1) and carbapenem (blaNDM-5) resistance genes, originally isolated in August 2014 from urine of a patient with recurrent urinary tract infections. To our knowledge, this is the first report in the United States of a clinical bacterial isolate with both colistin and carbapenem resistance, highlighting the importance of active surveillance efforts for colistin- and carbapenem-resistant organisms.

Contemporary Ventilator Management in Patients With and at Risk of ALI/ARDS

BACKGROUND: Ventilator practices in patients at risk for acute lung injury (ALI) and ARDS are unclear. We examined factors associated with choice of set tidal volumes (VT), and whether VT < 8 mL/kg predicted body weight (PBW) relates to the development of ALI/ARDS. METHODS: We performed a secondary analysis of a multicenter cohort of adult subjects at risk of lung injury with and without ALI/ARDS at onset of invasive ventilation. Descriptive statistics were used to describe ventilator practices in specific settings and ALI/ARDS risk groups. Logistic regression analysis was used to determine the factors associated with the use of VT < 8 mL/kg PBW and the relationship of VT to ALI/ARDS development and outcome. RESULTS: Of 829 mechanically ventilated patients, 107 met the criteria for ALI/ARDS at time of intubation, and 161 developed ALI/ARDS after intubation (post-intubation ALI/ARDS). There was significant intercenter variability in initial ventilator settings, and in the incidence of ALI/ARDS and post-intubation ALI/ARDS. The median VT was 7.96 (IQR 7.14–8.94) mL/kg PBW in ALI/ARDS subjects, and 8.45 (IQR 7.50–9.55) mL/kg PBW in subjects without ALI/ARDS (P = .004). VT decreased from 8.40 (IQR 7.38–9.37) mL/kg PBW to 7.97 (IQR 6.90–9.23) mL/kg PBW (P < .001) in those developing post-intubation ALI/ARDS. Among subjects without ALI/ARDS, VT ≥ 8 mL/kg PBW was associated with shorter height and higher body mass index, while subjects with pneumonia were less likely to get ≥ 8 mL/kg PBW. Initial VT ≥ 8 mL/kg PBW was not associated with the post-intubation ALI/ARDS (adjusted odds ratio 1.30, 95% CI 0.74–2.29) or worse outcomes. Post-intubation ALI/ARDS subjects had mortality similar to subjects intubated with ALI/ARDS. CONCLUSIONS: Clinicians seem to respond to ALI/ARDS with lower initial VT. Initial VT, however, was not associated with the development of post-intubation ALI/ARDS or other outcomes. (ClinicalTrials.gov registration NCT00889772)

Deaths Related to Nontuberculous Mycobacterial Infections in the United States, 1999–2014

RATIONALEnUnlike tuberculosis, nontuberculous mycobacterial disease is not reportable to public health authorities in the United States, and the total burden of disease is uncertain.nnnOBJECTIVESnTo estimate the mortality of nontuberculous mycobacterial disease in the United States over a 15-year period and to identify temporal trends.nnnMETHODSnThe U.S. Multiple Cause of Death Files from 1999 through 2014 were searched for a listing of nontuberculous mycobacterial disease by International Classification of Diseases, Tenth Revision code as either the underlying or a contributing cause of death. Characteristics of individuals with nontuberculous mycobacteria-related deaths in the United States were summarized according to demographic characteristics. Age-adjusted mortality rates and rate ratios were calculated using bridged-race population estimates of U.S. census population data. Time trends were evaluated with negative binomial regression.nnnMEASUREMENTS AND MAIN RESULTSnThere was a significant increase in nontuberculous mycobacteria-related deaths among individuals without a diagnosis of HIV infection (Pu2009=u20090.004). Mortality rates increased with advancing age. Age-adjusted mortality rate ratios were lower for men (risk ratio [RR], 0.84; 95% confidence interval [CI], 0.80-0.87) compared with women, and were lower for Hispanic individuals (RR, 0.53; 95% CI, 0.49-0.56) and black, non-Hispanic persons (RR, 0.83; 95% CI, 0.77-0.88) compared with white, non-Hispanic individuals.nnnCONCLUSIONSnThe mortality rate of nontuberculous mycobacterial disease among HIV-uninfected individuals has increased in the United States between 1999 and 2014. These deaths occurred disproportionately in older white women. Considering the concurrent decline in tuberculosis-related deaths, these findings demonstrate a shift in the epidemiology of fatal mycobacterial infections in the United States.

Medication errors with antituberculosis therapy in an inpatient, academic setting: forgotten but not gone

Tuberculosis, an infectious disease caused by the bacteria Mycobacterium tuberculosis, has significant public health implications. Despite the decreasing prevalence of tuberculosis cases and the availability of well‐established treatment guidelines, errors with antituberculosis medications remain a concern as clinician experience with the infection has waned and the goal of eradicating tuberculosis has remained unfulfilled. Whereas inappropriate use of other anti‐infective classes has been extensively studied, the evaluation of medication errors associated with antituberculosis therapy has been limited to a small number of studies conducted more than two decades ago. This study evaluated the prevalence of inpatient medication errors with antituberculosis therapy in patients with suspected or confirmed tuberculosis disease.

742Evaluation of Anti-Tuberculosis Medication Errors at an Urban University Hospital

Background. Combination therapy with Isoniazid, a Rifamycin, Pyrazinamide and Ethambutol is the standard of care for active tuberculosis (TB) treatment. Errors in medication administration could lead to inadvertent underdosing and resistance development, or significant side effects with overdosing. Given the recent nationwide focus on medication errors we attempted to establish the incidence of TB medication errors at University Hospital in Newark, NJ, a community with a relatively high prevalence of TB compared with the rest of the United States. Methods. A retrospective review of anti-TB medications prescribed during admissions between July 2010 June 2013 was conducted at University Hospital in Newark, NJ. Data was compared to the 2003 CDC guidelines for TB management. Medication errors were classified as improper drug regimen, incorrect dosing, incorrect medication adjustment for kidney and liver dysfunction and errors associated with concomitant highly active anti-retroviral therapy (HAART) use. We also categorized errors by consulting and admitting service at time of initiation. Results. A total of 72 admissions withsuspected, active TB were reviewed during the study period. 42 admissions (58%) had at least one error. Of the 63 total errors identified, the most common errors involved incorrect dosing of pyrazinamide (45%) followed by Ethambutol (25%). Of the 19 patients on concomitant HAART therapy, 37% were dosed incorrectly. Of the three patients in our study with creatinine clearance < 30 ml/minute, not one had appropriate renal dosing. Medication error rate was not significantly different whether the patient had an Infectious Disease (ID) consult (63.6%), a Pulmonology consult (57.4%), or both (61.3%). Conclusion. TB medication error rates are high among inpatients with suspected active TB despite frequent practice exposure. While this is the first recent study to evaluate inpatient anti-TB medication errors, our findings are consistent with those seen in studies of HIV medication errors at this institution and nationwide. The development of certain interventions, such as EMR reminders or mandatory pharmacist consults, could potentially reduce this error rate in the future. Disclosures. All authors: No reported disclosures.