Katherine Haffenreffer

Targeted versus Universal Decolonization to Prevent ICU Infection

BACKGROUND Both targeted decolonization and universal decolonization of patients in intensive care units (ICUs) are candidate strategies to prevent health care-associated infections, particularly those caused by methicillin-resistant Staphylococcus aureus (MRSA). METHODS We conducted a pragmatic, cluster-randomized trial. Hospitals were randomly assigned to one of three strategies, with all adult ICUs in a given hospital assigned to the same strategy. Group 1 implemented MRSA screening and isolation; group 2, targeted decolonization (i.e., screening, isolation, and decolonization of MRSA carriers); and group 3, universal decolonization (i.e., no screening, and decolonization of all patients). Proportional-hazards models were used to assess differences in infection reductions across the study groups, with clustering according to hospital. RESULTS A total of 43 hospitals (including 74 ICUs and 74,256 patients during the intervention period) underwent randomization. In the intervention period versus the baseline period, modeled hazard ratios for MRSA clinical isolates were 0.92 for screening and isolation (crude rate, 3.2 vs. 3.4 isolates per 1000 days), 0.75 for targeted decolonization (3.2 vs. 4.3 isolates per 1000 days), and 0.63 for universal decolonization (2.1 vs. 3.4 isolates per 1000 days) (P=0.01 for test of all groups being equal). In the intervention versus baseline periods, hazard ratios for bloodstream infection with any pathogen in the three groups were 0.99 (crude rate, 4.1 vs. 4.2 infections per 1000 days), 0.78 (3.7 vs. 4.8 infections per 1000 days), and 0.56 (3.6 vs. 6.1 infections per 1000 days), respectively (P<0.001 for test of all groups being equal). Universal decolonization resulted in a significantly greater reduction in the rate of all bloodstream infections than either targeted decolonization or screening and isolation. One bloodstream infection was prevented per 54 patients who underwent decolonization. The reductions in rates of MRSA bloodstream infection were similar to those of all bloodstream infections, but the difference was not significant. Adverse events, which occurred in 7 patients, were mild and related to chlorhexidine. CONCLUSIONS In routine ICU practice, universal decolonization was more effective than targeted decolonization or screening and isolation in reducing rates of MRSA clinical isolates and bloodstream infection from any pathogen. (Funded by the Agency for Healthcare Research and the Centers for Disease Control and Prevention; REDUCE MRSA ClinicalTrials.gov number, NCT00980980).

Validity of health plan and birth certificate data for pregnancy research

To evaluate the validity of health plan and birth certificate data for pregnancy research.

Medication Exposure in Pregnancy Risk Evaluation Program

To describe a program to study medication safety in pregnancy, the Medication Exposure in Pregnancy Risk Evaluation Program (MEPREP). MEPREP is a multi-site collaborative research program developed to enable the conduct of studies of medication use and outcomes in pregnancy. Collaborators include the U.S. Food and Drug Administration and researchers at the HMO Research Network, Kaiser Permanente Northern and Southern California, and Vanderbilt University. Datasets have been created at each site linking healthcare data for women delivering an infant between January 1, 2001 and December 31, 2008 and infants born to these women. Standardized data files include maternal and infant characteristics, medication use, and medical care at 11 health plans within 9 states; birth certificate data were obtained from the state departments of public health. MEPREP currently involves more than 20 medication safety researchers and includes data for 1,221,156 children delivered to 933,917 mothers. Current studies include evaluations of the prevalence and patterns of use of specific medications and a validation study of data elements in the administrative and birth certificate data files. MEPREP can support multiple studies by providing information on a large, ethnically and geographically diverse population. This partnership combines clinical and research expertise and data resources to enable the evaluation of outcomes associated with medication use during pregnancy.

Validation of an Algorithm to Estimate Gestational Age in Electronic Health Plan Databases

To validate an algorithm that uses delivery date and diagnosis codes to define gestational age at birth in electronic health plan databases.

Chlorhexidine and Mupirocin Susceptibility of Methicillin-Resistant Staphylococcus aureus Isolates in the REDUCE-MRSA Trial

ABSTRACT Whether targeted or universal decolonization strategies for the control of methicillin-resistant Staphylococcus aureus (MRSA) select for resistance to decolonizing agents is unresolved. The REDUCE-MRSA trial (ClinicalTrials registration no. NCT00980980) provided an opportunity to investigate this question. REDUCE-MRSA was a 3-arm, cluster-randomized trial of either screening and isolation without decolonization, targeted decolonization with chlorhexidine and mupirocin, or universal decolonization without screening to prevent MRSA infection in intensive-care unit (ICU) patients. Isolates from the baseline and intervention periods were collected and tested for susceptibility to chlorhexidine gluconate (CHG) by microtiter dilution; mupirocin susceptibility was tested by Etest. The presence of the qacA or qacB gene was determined by PCR and DNA sequence analysis. A total of 3,173 isolates were analyzed; 2 were nonsusceptible to CHG (MICs, 8 μg/ml), and 5/814 (0.6%) carried qacA or qacB. At baseline, 7.1% of MRSA isolates expressed low-level mupirocin resistance, and 7.5% expressed high-level mupirocin resistance. In a mixed-effects generalized logistic regression model, the odds of mupirocin resistance among clinical MRSA isolates or MRSA isolates acquired in an ICU in intervention versus baseline periods did not differ across arms, although estimates were imprecise due to small numbers. Reduced susceptibility to chlorhexidine and carriage of qacA or qacB were rare among MRSA isolates in the REDUCE-MRSA trial. The odds of mupirocin resistance were no different in the intervention versus baseline periods across arms, but the confidence limits were broad, and the results should be interpreted with caution.

Effect of body surface decolonisation on bacteriuria and candiduria in intensive care units: an analysis of a cluster-randomised trial

BACKGROUND Urinary tract infections (UTIs) are common health-care-associated infections. Bacteriuria commonly precedes UTI and is often treated with antibiotics, particularly in hospital intensive care units (ICUs). In 2013, a cluster-randomised trial (REDUCE MRSA Trial [Randomized Evaluation of Decolonization vs Universal Clearance to Eradicate MRSA]) showed that body surface decolonisation reduced all-pathogen bloodstream infections. We aim to further assess the effect of decolonisation on bacteriuria and candiduria in patients admitted to ICUs. METHODS We did a secondary analysis of a three-group, cluster-randomised trial of 43 hospitals (clusters) with patients in 74 adult ICUs. The three groups included were either meticillin-resistant Staphylococcus aureus (MRSA) screening and isolation, targeted decolonisation (screening, isolation, and decolonisation of MRSA carriers) with chlorhexidine and mupirocin, and universal decolonisation (no screening, all patients decolonised) with chlorhexidine and mupirocin. Protocol included chlorhexidine cleansing of the perineum and proximal 6 inches (15·24 cm) of urinary catheters. ICUs within the same hospital were assigned the same strategy. Outcomes included high-level bacteriuria (≥50 000 colony forming units [CFU]/mL) with any uropathogen, high-level candiduria (≥50 000 CFU/mL), and any bacteriuria with uropathogens. Sex-specific analyses were specified a priori. Proportional hazards models assessed differences in outcome reductions across groups, comparing an 18-month intervention period to a 12-month baseline period. FINDINGS 122 646 patients (48 390 baseline, 74 256 intervention) were enrolled. Intervention versus baseline hazard ratios (HRs) for high-level bacteriuria were 1·02 (95% CI 0·88-1·18) for screening or isolation, 0·88 (0·76-1·02) for targeted decolonisation, and 0·87 (0·77-1·00) for universal decolonisation (no difference between groups, p=0·26), with no sex-specific reductions (HRs for men: 1·09 [95% CI 0·85-1·40] for screening or isolation, 1·01 [0·79-1·29] for targeted decolonisation, and 0·78 [0·63-0·98] for universal decolonisation, p=0·12; HRs for women: 0·97 [0·80-1·17] for screening and isolation, 0·83 [0·70-1·00] for targeted decolonisation, and 0·93 [0·79-1·09] for universal decolonisation, p=0·49). HRs for high-level candiduria were 1·14 (0·95-1·37) for screening and isolation, 0·99 (0·83-1·18) for targeted decolonisation, and 0·83 (0·70-0·99) for universal decolonisation (p=0·05). Differences between sexes were due to reductions in men in the universal decolonisation group (HRs: 1·21 [95% CI 0·88-1·68] for screening or isolation, 1·01 [0·73-1·39] for targeted decolonisation, and 0·63 [0·45-0·89] for universal decolonisation, p=0·02). Bacteriuria with any CFU/mL was also reduced in men in the universal decolonisation group (HRs 1·01 [0·81-1·25] for screening or isolation, 1·04 [0·83-1·30] for targeted decolonisation, and 0·74 [0·61-0·90] for universal decolonisation, p=0·04). INTERPRETATION Universal decolonisation of patients in the ICU with once a day chlorhexidine baths and short-course nasal mupirocin could be a potential preventive strategy in male patients because it significantly decreases candiduria and any bacteriuria, but not for women. FUNDING HAI Program from AHRQ, US Department of Health and Human Services as part of the Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) program, CDC Prevention Epicenters Program.

Does Chlorhexidine Bathing in Adult Intensive Care Units Reduce Blood Culture Contamination? A Pragmatic Cluster-Randomized Trial

OBJECTIVE To determine rates of blood culture contamination comparing 3 strategies to prevent intensive care unit (ICU) infections: screening and isolation, targeted decolonization, and universal decolonization. DESIGN Pragmatic cluster-randomized trial. SETTING Forty-three hospitals with 74 ICUs; 42 of 43 were community hospitals. PATIENTS Patients admitted to adult ICUs from July 1, 2009, to September 30, 2011. METHODS After a 6-month baseline period, hospitals were randomly assigned to 1 of 3 strategies, with all participating adult ICUs in a given hospital assigned to the same strategy. Arm 1 implemented methicillin-resistant Staphylococcus aureus (MRSA) nares screening and isolation, arm 2 targeted decolonization (screening, isolation, and decolonization of MRSA carriers), and arm 3 conducted no screening but universal decolonization of all patients with mupirocin and chlorhexidine (CHG) bathing. Blood culture contamination rates in the intervention period were compared to the baseline period across all 3 arms. RESULTS During the 6-month baseline period, 7,926 blood cultures were collected from 3,399 unique patients: 1,099 sets in arm 1, 928 in arm 2, and 1,372 in arm 3. During the 18-month intervention period, 22,761 blood cultures were collected from 9,878 unique patients: 3,055 sets in arm 1, 3,213 in arm 2, and 3,610 in arm 3. Among all individual draws, for arms 1, 2, and 3, the contamination rates were 4.1%, 3.9%, and 3.8% for the baseline period and 3.3%, 3.2%, and 2.4% for the intervention period, respectively. When we evaluated sets of blood cultures rather than individual draws, the contamination rate in arm 1 (screening and isolation) was 9.8% (N = 108 sets) in the baseline period and 7.5% (N = 228) in the intervention period. For arm 2 (targeted decolonization), the baseline rate was 8.4% (N = 78) compared to 7.5% (N = 241) in the intervention period. Arm 3 (universal decolonization) had the greatest decrease in contamination rate, with a decrease from 8.7% (N = 119) contaminated blood cultures during the baseline period to 5.1% (N = 184) during the intervention period. Logistic regression models demonstrated a significant difference across the arms when comparing the reduction in contamination between baseline and intervention periods in both unadjusted (P = .02) and adjusted (P = .02) analyses. Arm 3 resulted in the greatest reduction in blood culture contamination rates, with an unadjusted odds ratio (OR) of 0.56 (95% confidence interval [CI], 0.044-0.71) and an adjusted OR of 0.55 (95% CI, 0.43-0.71). CONCLUSION In this large cluster-randomized trial, we demonstrated that universal decolonization with CHG bathing resulted in a significant reduction in blood culture contamination.

Methods of linking mothers and infants using health plan data for studies of pregnancy outcomes

Research on medication safety in pregnancy often utilizes health plan and birth certificate records. This study discusses methods used to link mothers with infants, a crucial step in such research.

Antiemetic use among pregnant women in the United States: the escalating use of ondansetron

To examine ondansetron use in pregnancy in the context of other antiemetic use among a large insured United States population of women delivering live births.

Trimethoprim–sulfonamide use during the first trimester of pregnancy and the risk of congenital anomalies

Sulfonamide antibacterials are widely used in pregnancy, but evidence about their safety is mixed. The objective of this study was to assess the association between first‐trimester sulfonamide exposure and risk of specific congenital malformations.