Linda M. Mundy

Emergence of New Delhi metallo-β-lactamase type 1-producing Enterobacteriaceae and non-Enterobacteriaceae: global case detection and bacterial surveillance

OBJECTIVEnA systematic review of the literature was conducted to summarize the descriptive and molecular epidemiology of human cases and surveillance reports with New Delhi metallo-β-lactamase type 1 (NDM-1)-producing bacteria reported worldwide from January 2008 through July 6, 2011.nnnMETHODSnA comprehensive literature review was conducted to identify publications of NDM-1-producing bacteria. Studies were divided into two broad categories of (1) case series and case reports of NDM-1-producing bacteria, or (2) active surveillance and environmental surveillance studies of NDM-1-producing bacteria.nnnRESULTSnSixty cases with NDM-1-producing bacteria were reported in the 3.5-year interval since the index case detection. The majority of reported cases represented colonization without evidence of infection (n=39, 65%); urine was the most common specimen source for cases with infection (41.7%) and colonization (33.3%). Seventeen cases (28.3%) had NDM-1-producing bacteria at more than one body site. Klebsiella pneumoniae and Escherichia coli were the most frequent bacteria detected, and the multilocus sequence type data from 34 E. coli and K. pneumoniae clinical isolates provided an incomplete, yet heterogeneous global distribution of NDM-1-producing bacteria. The majority of cases (63.3%) had exposure to the Indian subcontinent of south central Asia, and laboratory surveillance systems, as well as an environmental survey from India, suggest a presence of environmental reservoirs for potential human infection and colonization with NDM-1-producing bacteria.nnnCONCLUSIONSnThe majority of case reports with NDM-1-producing bacteria had presumed colonization, not infection, with one or more bacteria. The available human case reports and surveillance data suggest a global distribution of NDM-1-producing Enterobacteriaceae and non-Enterobacteriaceae.

The high comorbidity burden of the hepatitis C virus infected population in the United States

BackgroundChronic hepatitis C (HCV) disease can be complicated with comorbid conditions that may impact treatment eligibility and outcomes. The aim of the study was to systematically review comorbidities and symptoms in an HCV infected population, specifically assessing comorbidities associated with HCV anti-viral treatment and disease, as well as comparing comorbidities between an HCV infected and uninfected control population.MethodsThis was a retrospective cohort study within a United States medical claims database among patients with chronic HCV designed to estimate the two-year period prevalence of comorbidities. Patients with two HCV diagnosis codes, 24 months of continuous health insurance coverage, and full medical and pharmacy benefits were included.ResultsAmong a chronic HCV cohort of 7411 patients, at least one comorbid condition was seen in almost all patients (> 99%) during the study period. HCV-infected patients reported almost double the number of comorbidities compared to uninfected controls. Of the 25 most common comorbidities, the majority of the comorbidities (n = 22) were known to be associated with either HCV antiviral treatment or disease. The five most frequent comorbidities were liver disease [other] (37.5%), connective tissue disease (37.5%), abdominal pain (36.1%), upper respiratory infections (35.6%), and lower respiratory disease (33.7%). Three notable comorbidities not known to be associated with antiviral treatment or disease were benign neoplasms (24.3%), genitourinary symptoms & ill-defined conditions (14.8%), and viral infections (13.8%).ConclusionsThis US medically insured HCV population is highly comorbid. Effective strategies to manage these comorbidities are necessary to allow wider access to HCV treatment and reduce the future burden of HCV disease and its manifestations.

Colistin-based treatment for extensively drug-resistant Acinetobacter baumannii pneumonia☆

Data for treatment and outcomes of extensively drug-resistant Acinetobacter baumannii (XDR-AB) pneumonia are limited. A retrospective cohort study of 236 adult patients with XDR-AB pneumonia was conducted between January 2009 and December 2012. The median age of subjects was 70 years (range 17-95 years), 53% were male, 55% had ventilator-associated pneumonia and 42% had been admitted to the intensive care unit. All XDR-AB isolates were susceptible only to tigecycline and colistin; 52 (22%) of the 236 subjects did not receive an agent active against XDR-AB, with an associated 28-day survival of 0%. Colistin-based two-drug combination treatment was prescribed to 166 subjects (70%); regimens included (i) colistin and high-dose sulbactam (n=93); (ii) colistin and tigecycline (n=43); and (iii) colistin and high-dose prolonged infusion of a carbapenem (n=30). The 28-day survival rate and mean length of hospital stay were not statistically different between these three regimens (65%, 53% and 60% and 39, 39 and 38 days, respectively). Predictors of mortality included Acute Physiology and Chronic Health Evaluation (APACHE) II score [adjusted odds ratio (aOR)=1.11; P<0.001 for each point increase], duration from infection onset to receipt of active regimen (aOR=1.01; P=0.002 for each hour delay), underlying malignancy (aOR=3.46; P=0.01) and chronic kidney disease (aOR=2.85; P=0.03). These findings suggest that the three colistin-based two-drug combination regimens may be treatment options for XDR-AB pneumonia.

Overall benefit of antiretroviral treatment on the risk of fracture in HIV: nested case-control analysis in a health-insured population.

Objectives:Fractures are common and associated with multiple risk factors. We assessed the risks of fracture associated with time-dependent, differential antiretroviral drug exposures among a cohort of persons with HIV infection. Design:Nested case–control study from an HIV cohort of 59u200a594 medically insured persons with HIV infection enrolled in a medical care between January 1997 and March 2008. Methods:Cases were participants with a low-impact, nontraumatic fracture identified by ICD-9-CM codes; noncases were 1u200a:u200a4 matched and without fracture. Results:Cases included 2477 persons with HIV infection with fractures, who were risk-set matched to 9144 persons with HIV infection without fractures. Exposure to antiretroviral therapy by drug class and by duration (any drug/class) was associated with reduced risk for fracture. Drug-specific antiretroviral exposures over time identified an increased risk for fracture associated with darunavir, delavirdine and saquinavir, whereas reduced risk was associated with efavirenz, emtricitabine, lamivudine, tenofovir, and zidovudine. An initial null risk became a reduced risk with increased duration for nevirapine. In a similar pattern, abacavir, didanosine, nelfinavir, ritonavir and stavudine were initially associated with increased risk for fracture, after which the risk became null with increased duration of exposure. Null or uncertain risk for fracture was associated with amprenavir, atazanavir, enfuvirtide, fosamprenavir, indinavir, lopinavir, tipranavir, and zalcitabine. Conclusion:Our findings suggest an overall reduced risk for facture in persons treated versus not treated with antiretroviral drugs for HIV infection. Differential drug-specific exposure–response relationships for fracture will need to be further evaluated in other study populations.

Carbapenem-resistant Gram-negative bacteria: how to prioritize infection prevention and control interventions in resource-limited settings?

Emergences of carbapenem-resistant Gram-negative bacteria (CRGNB) have heightened global awareness of the prioritization of infection prevention and control (IPC) interventions to minimize infections attributed to these bacteria. Effective new antibiotic drugs for CRGNB are estimated to be at least 5 years off completion of trials and approval for use. Hence, effective IPC strategies remain at the core of clinical care and research for patients with CRGNB infection. The authors summarize current evidence and viewpoints for IPC strategies as related to the emergence, transmission and prevention of CRGNB.

Systematic Review and Meta-Analysis of Antimicrobial Treatment Effect Estimation in Complicated Urinary Tract Infection

ABSTRACT Noninferiority trial design and analyses are commonly used to establish the effectiveness of a new antimicrobial drug for treatment of serious infections such as complicated urinary tract infection (cUTI). A systematic review and meta-analysis were conducted to estimate the treatment effects of three potential active comparator drugs for the design of a noninferiority trial. The systematic review identified no placebo trials of cUTI, four clinical trials of cUTI with uncomplicated urinary tract infection as a proxy for placebo, and nine trials with reports of treatment effect estimates for doripenem, levofloxacin, or imipenem-cilastatin. In the meta-analysis, the primary efficacy endpoint of interest was the microbiological eradication rate at the test-of-cure visit in the microbiological intent-to-treat population. The estimated eradication rates and corresponding 95% confidence intervals (CI) were 31.8% (26.5% to 37.2%) for placebo, 81% (77.7% to 84.2%) for doripenem, 79% (75.9% to 82.2%) for levofloxacin, and 80.5% (71.9% to 89.1%) for imipenem-cilastatin. The treatment effect estimates were 40.5% for doripenem, 38.7% for levofloxacin, 34.7% for imipenem-cilastatin, and 40.8% overall. These treatment effect estimates can be used to inform the design and analysis of future noninferiority trials in cUTI study populations.

Tuberculin skin test and QuantiFERON-TB Gold In-tube Test for latent tuberculosis in Thai HIV-infected adults

Limited data exist for the performance of QuantiFERON‐TB Gold In‐tube Test (QFT‐IT) in comparison to tuberculin skin test (TST) for detecting latent tuberculosis (LTB) in patients with human immunodeficiency virus (HIV) infection from tuberculosis (TB)‐endemic Asia‐Pacific countries.

Design and analysis of a pharmacist-enhanced antimicrobial stewardship program in Thailand

BACKGROUNDnThe purpose of this study was to design and evaluate the enhancement of an antibiotic stewardship program (ASP) with trained hospital-based infectious diseases clinical pharmacists (IDCPs).nnnMETHODSnThe IDCP training entailed a 12-hour course by 3 pharmacists. From January 1, 2012-September 30, 2012, all patients consecutively admitted with presumptive infections to 6 medicine units were prospectively followed to discharge. Standard of care (SoC) included ASP measures with or without infectious diseases consultations (IDCs). Physician teams had the option to request IDCs, IDCPs, or both. The IDCP support included pharmacist participation in daily rounds to inform on antibiotic use. Outcomes examined were inappropriate antibiotic use, antibiotic de-escalation, duration of antibiotic use, and hospital length of stay (LOS) stratified by patient groups who received SoC versus adjunctive IDCPs with and without IDCs.nnnRESULTSnThere were 150 patients in the SoC group, 104 in the IDCP group, and 320 in the IDCP plus IDC group. Most antibiotic prescriptions were for empirical therapy (nxa0=xa0373, 65%), and the top-ranked indications were infections of the respiratory tract (nxa0=xa0287, 50%) and urinary tract (nxa0=xa0165, 29%). By multivariate analysis, compared with SoC, the 2 other groups were less likely to be prescribed inappropriate antibiotic use (Pxa0<xa0.001), had de-escalation of antibiotics (Pxa0<xa0.001), received antibiotics <7xa0days (Pxa0<xa0.001), and had subjects with shorter hospital LOSs (Pxa0<xa0.001). There were no group differences in mortality.nnnCONCLUSIONnOur study suggests measurable treatment benefits associated with international IDCP training and the integration of adjunct IDCP services into hospital-based ASPs.

Hospital Infection Prevention and Control Issues Relevant to Extensive Floods

The devastating clinical and economic implications of floods exemplify the need for effective global infection prevention and control (IPC) strategies for natural disasters. Reopening of hospitals after excessive flooding requires a balance between meeting the medical needs of the surrounding communities and restoration of a safe hospital environment. Postflood hospital preparedness plans are a key issue for infection control epidemiologists, healthcare providers, patients, and hospital administrators. We provide recent IPC experiences related to reopening of a hospital after extensive black-water floods necessitated hospital closures in Thailand and the United States. These experiences provide a foundation for the future design, execution, and analysis of black-water flood preparedness plans by IPC stakeholders.

Behavior-Based Interventions to Improve Hand Hygiene Adherence Among Intensive Care Unit Healthcare Workers in Thailand

OBJECTIVEnTo evaluate behavioral-based interventions to improve hand hygiene (HH) among healthcare workers (HCWs) at a Thai tertiary care center.nnnMETHODSnA quasi-experimental study was performed in 6 intensive care units with computer-generated allocation. Baseline demographic characteristics, self-reported stage of HH behavioral commitment, and observed HH adherence were examined from January 1, 2012, through December 31, 2012 (preintervention), and from January 1, 2013, through December 31, 2013 (postintervention). Self-reported HH was categorized by the stages construct from the Transtheoretical Model of Health Behavior Change. The intensive care unit group randomization was to either standard-of-care HH education every 3 months (S1), intensified HH interventions (S2), or intensified HH interventions plus increased availability of alcohol-based handrub throughout the unit (S3).nnnRESULTSnAmong 125 HCWs from 6 intensive care units (42 in S1, 41 in S2, 42 in S3) there were 1,936 total HH observations; most HCWs (100 [ 80%]) were nurses or nurse assistants. Compared with preintervention, overall postintervention HH adherence improved in HCWs assigned to S2 (65% vs 85%; P=.02) and S3 (66% vs 95%; P=.005) but not S1 (68% vs 71%; P=.84). Improvement in HH adherence was demonstrated among HCWs who reported lower stages of HH commitment in S2 (21% vs 84%; P<.001) and S3 (24% vs 89%; P<.001) and in HCWs who self-reported higher stages of commitment in S3 (78% vs 96%; P<.001).nnnCONCLUSIONSnHCW HH programs may benefit from stage-based tailored strategies to promote sustained HH adherence.