Daniel J. Morgan

Non-prescription antimicrobial use worldwide: a systematic review

In much of the world antimicrobial drugs are sold without prescription or oversight by health-care professionals. The scale and effect of this practice is unknown. We systematically reviewed published works about non-prescription antimicrobials from 1970-2009, identifying 117 relevant articles. 35 community surveys from five continents showed that non-prescription use occurred worldwide and accounted for 19-100% of antimicrobial use outside of northern Europe and North America. Safety issues associated with non-prescription use included adverse drug reactions and masking of underlying infectious processes. Non-prescription use was common for non-bacterial disease, and antituberculosis drugs were available in many areas. Antimicrobial-resistant bacteria are common in communities with frequent non-prescription use. In a few settings, control efforts that included regulation decreased antimicrobial use and resistance. Non-prescription antimicrobial and antituberculosis use is common outside of North America and northern Europe and must be accounted for in public health efforts to reduce antimicrobial resistance.

Adverse outcomes associated with contact precautions: A review of the literature

BACKGROUND Contact Precautions (CP) are a standard method for preventing patient-to-patient transmission of multiple drug-resistant organisms (MDROs) in hospital settings. With the ongoing worldwide concern for MDROs including methicillin-resistant Staphylococcus aureus (MRSA) and broadened use of active surveillance programs, an increasing number of patients are being placed on CP. Whereas few would argue that CP are an important tool in infection control, many reports and small studies have observed worse noninfectious outcomes in patients on CP. However, no review of this literature exists. METHODS We systematically reviewed the literature describing adverse outcomes associated with CP. We identified 15 studies published between 1989 and 2008 relating to adverse outcomes from CP. Nine were higher quality based on standardized collection of data and/or inclusion of control groups. RESULTS Four main adverse outcomes related to CP were identified in this review. These included less patient-health care worker contact, changes in systems of care that produce delays and more noninfectious adverse events, increased symptoms of depression and anxiety, and decreased patient satisfaction with care. CONCLUSION Although CP are recommended by the Centers for Disease Control and Prevention as an intervention to control spread of MDROs, our review of the literature demonstrates that this approach has unintended consequences that are potentially deleterious to the patient. Measures to ameliorate these deleterious consequences of CP are urgently needed.

Frequent Multidrug-Resistant Acinetobacter baumannii Contamination of Gloves, Gowns, and Hands of Healthcare Workers

BACKGROUND Multidrug-resistant (MDR) gram-negative bacilli are important nosocomial pathogens. OBJECTIVE To determine the incidence of transmission of MDR Acinetobacter baumannii and Pseudomonas aeruginosa from patients to healthcare workers (HCWs) during routine patient care. DESIGN Prospective cohort study. SETTING Medical and surgical intensive care units. Methods. We observed HCWs who entered the rooms of patients colonized with MDR A. baumannii or colonized with both MDR A. baumannii and MDR P. aeruginosa. We examined their hands before room entry, their disposable gloves and/or gowns upon completion of patient care, and their hands after removal of gloves and/or gowns and before hand hygiene. RESULTS Sixty-five interactions occurred with patients colonized with MDR A. baumannii and 134 with patients colonized with both MDR A. baumannii and MDR P. aeruginosa. Of 199 interactions between HCWs and patients colonized with MDR A. baumannii, 77 (38.7% [95% confidence interval {CI}, 31.9%-45.5%]) resulted in HCW contamination of gloves and/or gowns, and 9 (4.5% [95% CI, 1.6%-7.4%]) resulted in contamination of HCW hands after glove removal before hand hygiene. Of 134 interactions with patients colonized with MDR P. aeruginosa, 11 (8.2% [95% CI, 3.6%-12.9%]) resulted in HCW contamination of gloves and/or gowns, and 1 resulted in HCW contamination of hands. Independent risk factors for contamination with MDR A. baumannii were manipulation of wound dressing (adjusted odds ratio [aOR], 25.9 [95% CI, 3.1-208.8]), manipulation of artificial airway (aOR, 2.1 [95% CI, 1.1-4.0]), time in room longer than 5 minutes (aOR, 4.3 [95% CI, 2.0-9.1]), being a physician or nurse practitioner (aOR, 7.4 [95% CI, 1.6-35.2]), and being a nurse (aOR, 2.3 [95% CI, 1.1-4.8]). CONCLUSIONS Gowns, gloves, and unwashed hands of HCWs were frequently contaminated with MDR A. baumannii. MDR A. baumannii appears to be more easily transmitted than MDR P. aeruginosa and perhaps more easily transmitted than previously studied methicillin-resistant Staphylococcus aureus or vancomycin-resistant Enterococcus. This ease of transmission may help explain the emergence of MDR A. baumannii.

Transfer of multidrug-resistant bacteria to healthcare workers' gloves and gowns after patient contact increases with environmental contamination.

Objective:To assess the role of environmental contamination in the transmission of multidrug-resistant bacteria to healthcare workers’ clothing. Design:Prospective cohort. Setting:Six intensive care units at a tertiary care hospital. Subjects:Healthcare workers including registered nurses, patient care technicians, respiratory therapists, occupational/physical therapists, and physicians. Interventions:None. Measurements and Main Results:One hundred twenty of 585 (20.5%) healthcare worker/patient interactions resulted in contamination of healthcare workers’ gloves or gowns. Multidrug-resistant Acinetobacter baumannii contamination occurred most frequently, 55 of 167 observations (32.9%; 95% confidence interval [CI] 25.8% to 40.0%), followed by multidrug-resistant Pseudomonas aeruginosa, 15 of 86 (17.4%; 95% CI 9.4% to 25.4%), vancomycin-resistant Enterococcus, 25 of 180 (13.9%, 95% CI 8.9, 18.9%) and methicillin-resistant Staphylococcus aureus, 21 of 152 (13.8%; 95% CI 8.3% to 19.2%). Independent risk factors associated with healthcare worker contamination with multidrug-resistant bacteria were positive environmental cultures (odds ratio [OR] 4.2; 95% CI 2.7–6.5), duration in room for >5 mins (OR 2.0; 95% CI 1.2–3.4), performing physical examinations (OR 1.7; 95% CI 1.1–2.8), and contact with the ventilator (OR 1.8; 95% CI, 1.1–2.8). Pulsed field gel electrophoresis determined that 91% of healthcare worker isolates were related to an environmental or patient isolate. Conclusions:The contamination of healthcare workers’ protective clothing during routine care of patients with multidrug-resistant organisms is most frequent with A. baumannii. Environmental contamination was the major determinant of transmission to healthcare workers’ gloves or gowns. Compliance with contact precautions and more aggressive environmental cleaning may decrease transmission.

Clinical outcomes of patients with Klebsiella pneumoniae carbapenemase-producing K. pneumoniae after treatment with imipenem or meropenem

Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae may appear susceptible to imipenem or meropenem by routine susceptibility testing. We report a series of patients with infections caused by K. pneumoniae isolates, which yielded imipenem-susceptible results but were subsequently KPC-positive by polymerase chain reaction. When these infections were treated with imipenem or meropenem, frequent clinical and microbiologic failures were observed.

Potential burden of antibiotic resistance on surgery and cancer chemotherapy antibiotic prophylaxis in the USA: a literature review and modelling study.

BACKGROUND The declining efficacy of existing antibiotics potentially jeopardises outcomes in patients undergoing medical procedures. We investigated the potential consequences of increases in antibiotic resistance on the ten most common surgical procedures and immunosuppressing cancer chemotherapies that rely on antibiotic prophylaxis in the USA. METHODS We searched the published scientific literature and identified meta-analyses and reviews of randomised controlled trials or quasi-randomised controlled trials (allocation done on the basis of a pseudo-random sequence-eg, odd/even hospital number or date of birth, alternation) to estimate the efficacy of antibiotic prophylaxis in preventing infections and infection-related deaths after surgical procedures and immunosuppressing cancer chemotherapy. We varied the identified effect sizes under different scenarios of reduction in the efficacy of antibiotic prophylaxis (10%, 30%, 70%, and 100% reductions) and estimated the additional number of infections and infection-related deaths per year in the USA for each scenario. We estimated the percentage of pathogens causing infections after these procedures that are resistant to standard prophylactic antibiotics in the USA. FINDINGS We estimate that between 38·7% and 50·9% of pathogens causing surgical site infections and 26·8% of pathogens causing infections after chemotherapy are resistant to standard prophylactic antibiotics in the USA. A 30% reduction in the efficacy of antibiotic prophylaxis for these procedures would result in 120,000 additional surgical site infections and infections after chemotherapy per year in the USA (ranging from 40,000 for a 10% reduction in efficacy to 280,000 for a 70% reduction in efficacy), and 6300 infection-related deaths (range: 2100 for a 10% reduction in efficacy, to 15,000 for a 70% reduction). We estimated that every year, 13,120 infections (42%) after prostate biopsy are attributable to resistance to fluoroquinolones in the USA. INTERPRETATION Increasing antibiotic resistance potentially threatens the safety and efficacy of surgical procedures and immunosuppressing chemotherapy. More data are needed to establish how antibiotic prophylaxis recommendations should be modified in the context of increasing rates of resistance. FUNDING DRIVE-AB Consortium.

Trends in Resistance to Carbapenems and Third-Generation Cephalosporins among Clinical Isolates of Klebsiella pneumoniae in the United States, 1999–2010

OBJECTIVE Multidrug-resistant Enterobacteriaceae pose a serious infection control challenge and have emerged as a public health threat. We examined national trends in the proportion of Klebsiella pneumoniae isolates resistant to carbapenems (CRKP) and third-generation cephalosporins (G3CRKP). DESIGN AND SETTING Retrospective analysis of approximately 500,000 K. pneumoniae isolates cultured between January 1999 and July 2010 at 287 clinical laboratories throughout the United States. METHODS Isolates were defined as CRKP if they were nonsusceptible to 1 or more carbapenems and were defined as G3CRKP if they were nonsusceptible to ceftazidime, ceftriaxone, or related antibiotics. A multivariable analysis examined trends in the proportion of resistant isolates, adjusting for age, sex, isolate source, patient location, and geographic region. RESULTS The crude proportion of CRKP increased from less than 0.1% to 4.5% between 2002 and 2010; the frequency of G3CRKP increased from 5.3% to 11.5% between 1999 and 2010. G3CRKP and CRKP were more common among elderly patients (those greater than 65 years of age); the adjusted odds ratio (aOR) relative to pediatric patients (those less than 18 years of age) was 1.2 for G3CRKP (95% confidence interval [CI], 1.2-1.3) and 3.3 for CRKP (95% CI, 2.6-4.2). G3CRKP and CRKP were also more common among patients from the northeastern United States (aOR, 2.9 [95% CI, 2.8-3.0] and 9.0 [95% CI, 7.9-10.4]) than among those from the western United States. The prevalence of outpatient CRKP isolates increased after 2006, reaching 1.9% of isolates in our sample in 2010 (95% CI, 1.6%-2.1%). CONCLUSIONS The frequency of G3CRKP and CRKP is increasing in all regions of the United States, and resistance is emerging among isolates recovered in the outpatient setting. This underscores the need for enhanced laboratory capacity and coordinated surveillance strategies to contain the further spread of these emerging pathogens.

Setting a research agenda for medical overuse

Although overuse in medicine is gaining increased attention, many questions remain unanswered. Dan Morgan and colleagues propose an agenda for coordinated research to improve our understanding of the problem

Reconsidering contact precautions for endemic methicillin-resistant staphylococcus aureus and vancomycin-resistant enterococcus

BACKGROUND Whether contact precautions (CP) are required to control the endemic transmission of methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE) in acute care hospitals is controversial in light of improvements in hand hygiene, MRSA decolonization, environmental cleaning and disinfection, fomite elimination, and chlorhexidine bathing. OBJECTIVE To provide a framework for decision making around use of CP for endemic MRSA and VRE based on a summary of evidence related to use of CP, including impact on patients and patient care processes, and current practices in use of CP for MRSA and VRE in US hospitals. DESIGN A literature review, a survey of Society for Healthcare Epidemiology of America Research Network members on use of CP, and a detailed examination of the experience of a convenience sample of hospitals not using CP for MRSA or VRE. PARTICIPANTS Hospital epidemiologists and infection prevention experts. RESULTS No high quality data support or reject use of CP for endemic MRSA or VRE. Our survey found more than 90% of responding hospitals currently use CP for MRSA and VRE, but approximately 60% are interested in using CP in a different manner. More than 30 US hospitals do not use CP for control of endemic MRSA or VRE. CONCLUSIONS Higher quality research on the benefits and harms of CP in the control of endemic MRSA and VRE is needed. Until more definitive data are available, the use of CP for endemic MRSA or VRE in acute care hospitals should be guided by local needs and resources.

Assessment of empirical antibiotic therapy optimisation in six hospitals: an observational cohort study

BACKGROUND Modification of empirical antimicrobials when warranted by culture results or clinical signs is recommended to control antimicrobial overuse and resistance. We aimed to assess the frequency with which patients were started on empirical antimicrobials, characteristics of the empirical regimen and the clinical characteristics of patients at the time of starting antimicrobials, patterns of changes to empirical therapy at different timepoints, and modifiable factors associated with changes to the initial empirical regimen in the first 5 days of therapy. METHODS We did a chart review of adult inpatients receiving one or more antimicrobials in six US hospitals on 4 days during 2009 and 2010. Our primary outcome was the modification of antimicrobial regimen on or before the 5th day of empirical therapy, analysed as a three-category variable. Bivariate analyses were used to establish demographic and clinical variables associated with the outcome. Variables with p values below 0·1 were included in a multivariable generalised linear latent and mixed model with multinomial logit link to adjust for clustering within hospitals and accommodate a non-binary outcome variable. FINDINGS Across the six study sites, 4119 (60%) of 6812 inpatients received antimicrobials. Of 1200 randomly selected patients with active antimicrobials, 730 (61%) met inclusion criteria. At the start of therapy, 220 (30%) patients were afebrile and had normal white blood cell counts. Appropriate cultures were collected from 432 (59%) patients, and 250 (58%) were negative. By the 5th day of therapy, 12·5% of empirical antimicrobials were escalated, 21·5% were narrowed or discontinued, and 66·4% were unchanged. Narrowing or discontinuation was more likely when cultures were collected at the start of therapy (adjusted OR 1·68, 95% CI 1·05-2·70) and no infection was noted on an initial radiological study (1·76, 1·11-2·79). Escalation was associated with multiple infection sites (2·54, 1·34-4·83) and a positive culture (1·99, 1·20-3·29). INTERPRETATION Broad-spectrum empirical therapy is common, even when clinical signs of infection are absent. Fewer than one in three inpatients have their regimens narrowed within 5 days of starting empirical antimicrobials. Improved diagnostic methods and continued education are needed to guide discontinuation of antimicrobials. FUNDING US Centers for Disease Control and Prevention, Division of Healthcare Quality Promotion; Robert Wood Johnson Foundation; US Department of Veterans Administration; US Department of Homeland Security.