To evaluate probiotics for the primary prevention of Clostridium difficile infection (CDI) among hospital inpatients.

A before-and-after quality improvement intervention comparing 12-month baseline and intervention periods.

A 694-bed teaching hospital.

We administered a multispecies probiotic comprising L. acidophilus (CL1285), L. casei (LBC80R), and L. rhamnosus (CLR2) to eligible antibiotic recipients within 12 hours of initial antibiotic receipt through 5 days after final dose. We excluded (1) all patients on neonatal, pediatric and oncology wards; (2) all individuals receiving perioperative prophylactic antibiotic recipients; (3) all those restricted from oral intake; and (4) those with pancreatitis, leukopenia, or posttransplant. We defined CDI by symptoms plus C. difficile toxin detection by polymerase chain reaction. Our primary outcome was hospital-onset CDI incidence on eligible hospital units, analyzed using segmented regression.

The study included 251 CDI episodes among 360,016 patient days during the baseline and intervention periods, and the incidence rate was 7.0 per 10,000 patient days. The incidence rate was similar during baseline and intervention periods (6.9 vs 7.0 per 10,000 patient days; P=.95). However, compared to the first 6 months of the intervention, we detected a significant decrease in CDI during the final 6 months (incidence rate ratio, 0.6; 95% confidence interval, 0.4–0.9; P=.009). Testing intensity remained stable between the baseline and intervention periods: 19% versus 20% of stools tested were C. difficile positive by PCR, respectively. From medical record reviews, only 26% of eligible patients received a probiotic per the protocol.

Despite poor adherence to the protocol, there was a reduction in the incidence of CDI during the intervention, which was delayed ~6 months after introducing probiotic for primary prevention.

Infect Control Hosp Epidemiol 2018;765–770

To determine whether probiotic prophylaxes reduce the odds of Clostridium difficile infection (CDI) in adults and children.

Individual participant data (IPD) meta-analysis of randomized controlled trials (RCTs), adjusting for risk factors.

We searched 6 databases and 11 grey literature sources from inception to April 2016. We identified 32 RCTs (n=8,713); among them, 18 RCTs provided IPD (n=6,851 participants) comparing probiotic prophylaxis to placebo or no treatment (standard care). One reviewer prepared the IPD, and 2 reviewers extracted data, rated study quality, and graded evidence quality.

Probiotics reduced CDI odds in the unadjusted model (n=6,645; odds ratio [OR] 0.37; 95% confidence interval [CI], 0.25–0.55) and the adjusted model (n=5,074; OR, 0.35; 95% CI, 0.23–0.55). Using 2 or more antibiotics increased the odds of CDI (OR, 2.20; 95% CI, 1.11–4.37), whereas age, sex, hospitalization status, and high-risk antibiotic exposure did not. Adjusted subgroup analyses suggested that, compared to no probiotics, multispecies probiotics were more beneficial than single-species probiotics, as was using probiotics in clinical settings where the CDI risk is ≥5%. Of 18 studies, 14 reported adverse events. In 11 of these 14 studies, the adverse events were retained in the adjusted model. Odds for serious adverse events were similar for both groups in the unadjusted analyses (n=4,990; OR, 1.06; 95% CI, 0.89–1.26) and adjusted analyses (n=4,718; OR, 1.06; 95% CI, 0.89–1.28). Missing outcome data for CDI ranged from 0% to 25.8%. Our analyses were robust to a sensitivity analysis for missingness.

Moderate quality (ie, certainty) evidence suggests that probiotic prophylaxis may be a useful and safe CDI prevention strategy, particularly among participants taking 2 or more antibiotics and in hospital settings where the risk of CDI is ≥5%.

PROSPERO 2015 identifier: CRD42015015701

Infect Control Hosp Epidemiol 2018;771–781

To determine the incidence and risk factors associated with Clostridium difficile colonization among residents of nursing homes and to identify the ribotypes of circulating C. difficile strains.

A prospective cohort study with a follow-up duration of 22 months.

Nursing homes.

Of the 375 residents in 8 nursing homes, 300 residents (80.0%) participated in the study. A further prospective study of 4 nursing homes involving 141 residents with a minimum of 90 days of follow-up was also performed.

Baseline and 90-day stool cultures were obtained; additional stool cultures were obtained for residents who had been discharged from hospitals. Polymerase chain reaction (PCR) ribotyping and slpA typing were performed for all C. difficile strains isolated.

Toxigenic C. difficile was isolated in 30 residents (10%) at baseline, and 9 residents (7.3%) had acquired toxigenic C. difficile in the nursing homes. The presence of nasogastric tube was an independent risk factor (adjusted odds ratio, 8.59; 95% confidence interval, 1.18–62.53; P=.034) for C. difficile colonization. The Kaplan-Meier estimate of median carriage duration was 13 weeks. The C. difficile ribotypes most commonly identified were 002 (40.8%), 014 (16.9%), 029 (9.9%), and 053 (8.5%).

The high incidence of C. difficile colonization and the overrepresentation of C. difficile ribotype 002 confirmed the contribution of nursing home residents to C. difficile transmission across the continuum of care. An infection control program is needed in long-term care.

Infect Control Hosp Epidemiol 2018;782–787

To evaluate the impact of discontinuing routine contact precautions (CP) for endemic methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) on hospital adverse events.

Retrospective, nonrandomized, observational, quasi-experimental study.

Academic medical center with single-occupancy rooms.

Inpatients.

We compared hospital reportable adverse events 1 year before and 1 year after discontinuation of routine CP for endemic MRSA and VRE (preintervention and postintervention periods, respectively). Throughout the preintervention period, daily chlorhexidine gluconate bathing was expanded to nearly all inpatients. Chart reviews were performed to identify which patients and events were associated with CP for MRSA/VRE in the preintervention period as well as the patients that would have met prior criteria for MRSA/VRE CP but were not isolated in the postintervention period. Adverse events during the 2 periods were compared using segmented and mixed-effects Poisson regression models.

There were 24,732 admissions in the preintervention period and 25,536 in the postintervention period. Noninfectious adverse events (ie, postoperative respiratory failure, hemorrhage/hematoma, thrombosis, wound dehiscence, pressure ulcers, and falls or trauma) decreased by 19% (12.3 to 10.0 per 1,000 admissions, P=.022) from the preintervention to the postintervention period. There was no significant difference in the rate of infectious adverse events after CP discontinuation (20.7 to 19.4 per 1,000 admissions, P=.33). Patients with MRSA/VRE showed the largest reduction in noninfectious adverse events after CP discontinuation, with a 72% reduction (21.4 to 6.08 per 1,000 MRSA/VRE admissions; P<.001).

After discontinuing routine CP for endemic MRSA/VRE, the rate of noninfectious adverse events declined, especially in patients who no longer required isolation. This suggests that elimination of CP may substantially reduce noninfectious adverse events.

Infect Control Hosp Epidemiol 2018;788–796

To explore the prevalence and drivers of hospital-level variability in antibiotic utilization among hematopoietic cell transplant (HCT) recipients to inform antimicrobial stewardship initiatives.

Retrospective cohort study using data merged from the Pediatric Health Information System and the Center for International Blood and Marrow Transplant Research.

The study included 27 transplant centers in freestanding children’s hospitals.

The primary outcome was days of broad-spectrum antibiotic use in the interval from day of HCT through neutrophil engraftment. Hospital antibiotic utilization rates were reported as days of therapy (DOTs) per 1,000 neutropenic days. Negative binomial regression was used to estimate hospital utilization rates, adjusting for patient covariates including demographics, transplant characteristics, and severity of illness. To better quantify the magnitude of hospital variation and to explore hospital-level drivers in addition to patient-level drivers of variation, mixed-effects negative binomial models were also constructed.

Adjusted hospital rates of antipseudomonal antibiotic use varied from 436 to 1121 DOTs per 1,000 neutropenic days, and rates of broad-spectrum, gram-positive antibiotic use varied from 153 to 728 DOTs per 1,000 neutropenic days. We detected variability by hospital in choice of antipseudomonal agent (ie, cephalosporins, penicillins, and carbapenems), but gram-positive coverage was primarily driven by vancomycin use. Considerable center-level variability remained even after controlling for additional hospital-level factors. Antibiotic use was not strongly associated with days of significant illness or mortality.

Among a homogenous population of children undergoing HCT for acute leukemia, both the quantity and spectrum of antibiotic exposure in the immediate posttransplant period varied widely. Antimicrobial stewardship initiatives can apply these data to optimize the use of antibiotics in transplant patients.

Infect Control Hosp Epidemiol 2018;797–805

To identify predictors of disagreement with antimicrobial stewardship prospective audit and feedback recommendations (PAFR) at a free-standing children’s hospital.

Retrospective cohort study of audits performed during the antimicrobial stewardship program (ASP) from March 30, 2015, to April 17, 2017.

The ASP included audits of antimicrobial use and communicated PAFR to the care team, with follow-up on adherence to recommendations. The primary outcome was disagreement with PAFR. Potential predictors for disagreement, including patient-level, antimicrobial, programmatic, and provider-level factors, were assessed using bivariate and multivariate logistic regression models.

In total, 4,727 antimicrobial audits were performed during the study period; 1,323 PAFR (28%) and 187 recommendations (15%) were not followed due to disagreement. Providers were more likely to disagree with PAFR when the patient had a gastrointestinal infection (odds ratio [OR], 5.50; 95% confidence interval [CI], 1.99–15.21), febrile neutropenia (OR, 6.14; 95% CI, 2.08–18.12), skin or soft-tissue infections (OR, 6.16; 95% CI, 1.92–19.77), or had been admitted for 31–90 days at the time of the audit (OR, 2.08; 95% CI, 1.36–3.18). The longer the duration since the attending provider had been trained (ie, the more years of experience), the more likely they were to disagree with PAFR recommendations (OR, 1.02; 95% CI, 1.01–1.04).

Evaluation of our program confirmed patient-level predictors of PAFR disagreement and identified additional programmatic and provider-level factors, including years of attending experience. Stewardship interventions focused on specific diagnoses and antimicrobials are unlikely to result in programmatic success unless these factors are also addressed.

Infect Control Hosp Epidemiol 2018;806–813

We conducted a randomized, parallel, unblinded, superiority trial of a laboratory reporting intervention designed to reduce antibiotic treatment of asymptomatic bacteriuria (ASB).

Results of positive urine cultures from 110 consecutive inpatients at 2 urban acute-care hospitals were randomized to standard report (control) or modified report (intervention). The standard report included bacterial count, bacterial identification, and antibiotic susceptibility information including drug dosage and cost. The modified report stated: “This POSITIVE urine culture may represent asymptomatic bacteriuria or urinary tract infection. If urinary tract infection is suspected clinically, please call the microbiology laboratory … for identification and susceptibility results.” We used the following exclusion criteria: age <18 years, pregnancy, presence of an indwelling urinary catheter, samples from patients already on antibiotics, neutropenia, or admission to an intensive care unit. The primary efficacy outcome was the proportion of appropriate antibiotic therapy prescribed.

According to our intention-to-treat (ITT) analysis, the proportion of appropriate treatment (urinary tract infection treated plus ASB not treated) was higher in the modified arm than in the standard arm: 44 of 55 (80.0%) versus 29 of 55 (52.7%), respectively (absolute difference, −27.3%; RR, 0.42; P = .002; number needed to report for benefit, 3.7).

Modified reporting resulted in a significant reduction in inappropriate antibiotic treatment without an increase in adverse events. Safety should be further assessed in a large effectiveness trial before implementation

TRIAL REGISTRATION. clinicaltrials.gov#NCT02797613

Infect Control Hosp Epidemiol 2018;814–819

Collaborative programs have helped reduce catheter-associated urinary tract infection (CAUTI) rates in community-based nursing homes. We assessed whether collaborative participation produced similar benefits among Veterans Health Administration (VHA) nursing homes, which are part of an integrated system.

This study included 63 VHA nursing homes enrolled in the “AHRQ Safety Program for Long-Term Care,” which focused on practices to reduce CAUTI.

Changes in CAUTI rates, catheter utilization, and urine culture orders were assessed from June 2015 through May 2016. Multilevel mixed-effects negative binomial regression was used to derive incidence rate ratios (IRRs) representing changes over the 12-month program period.

There was no significant change in CAUTI among VHA sites, with a CAUTI rate of 2.26 per 1,000 catheter days at month 1 and a rate of 3.19 at month 12 (incidence rate ratio [IRR], 0.99; 95% confidence interval [CI], 0.67–1.44). Results were similar for catheter utilization rates, which were 11.02% at month 1 and 11.30% at month 12 (IRR, 1.02; 95% CI, 0.95–1.09). The numbers of urine cultures per 1,000 residents were 5.27 in month 1 and 5.31 in month 12 (IRR, 0.93; 95% CI, 0.82–1.05).

No changes in CAUTI rates, catheter use, or urine culture orders were found during the program period. One potential reason was the relatively low baseline CAUTI rate, as compared with a cohort of community-based nursing homes. This low baseline rate is likely related to the VHA’s prior CAUTI prevention efforts. While broad-scale collaborative approaches may be effective in some settings, targeting higher-prevalence safety issues may be warranted at sites already engaged in extensive infection prevention efforts.

Infect Control Hosp Epidemiol 2018;820–825

To validate a system to detect ventilator associated events (VAEs) autonomously and in real time.

Retrospective review of ventilated patients using a secure informatics platform to identify VAEs (ie, automated surveillance) compared to surveillance by infection control (IC) staff (ie, manual surveillance), including development and validation cohorts.

The Massachusetts General Hospital, a tertiary-care academic health center, during January–March 2015 (development cohort) and January–March 2016 (validation cohort).

Ventilated patients in 4 intensive care units.

The automated process included (1) analysis of physiologic data to detect increases in positive end-expiratory pressure (PEEP) and fraction of inspired oxygen (FiO2); (2) querying the electronic health record (EHR) for leukopenia or leukocytosis and antibiotic initiation data; and (3) retrieval and interpretation of microbiology reports. The cohorts were evaluated as follows: (1) manual surveillance by IC staff with independent chart review; (2) automated surveillance detection of ventilator-associated condition (VAC), infection-related ventilator-associated complication (IVAC), and possible VAP (PVAP); (3) senior IC staff adjudicated manual surveillance–automated surveillance discordance. Outcomes included sensitivity, specificity, positive predictive value (PPV), and manual surveillance detection errors. Errors detected during the development cohort resulted in algorithm updates applied to the validation cohort.

In the development cohort, there were 1,325 admissions, 479 ventilated patients, 2,539 ventilator days, and 47 VAEs. In the validation cohort, there were 1,234 admissions, 431 ventilated patients, 2,604 ventilator days, and 56 VAEs. With manual surveillance, in the development cohort, sensitivity was 40%, specificity was 98%, and PPV was 70%. In the validation cohort, sensitivity was 71%, specificity was 98%, and PPV was 87%. With automated surveillance, in the development cohort, sensitivity was 100%, specificity was 100%, and PPV was 100%. In the validation cohort, sensitivity was 85%, specificity was 99%, and PPV was 100%. Manual surveillance detection errors included missed detections, misclassifications, and false detections.

Manual surveillance is vulnerable to human error. Automated surveillance is more accurate and more efficient for VAE surveillance.

Infect Control Hosp Epidemiol 2018;826–833

Worldwide, Mycobacterium chimaera infections have been linked to contaminated aerosols from heater-cooler units (HCUs) during open-heart surgery. These infections have mainly been associated with the 3T HCU (LivaNova, formerly Sorin). The reasons for this and the risk of transmission from other HCUs have not been systematically assessed.

Prospective observational study.

University Hospital Basel, Switzerland.

Continuous microbiological surveillance of 3 types of HCUs in use (3T from LivaNova/Sorin and HCU30 and HCU40 from Maquet) was initiated in June 2014, coupled with an epidemiologic workup. Monthly water and air samples were taken. Construction design was analyzed, and exhausted airflow was measured.

Mycobacterium chimaera grew in 8 of 12 water samples (66%) and 22 of 24 air samples (91%) of initial 3T HCUs in use, and in 2 of 83 water samples (2%) and 0 of 41 (0%) air samples of new replacement 3T HCUs. Moreover, 7 of 12 water samples (58%) and 0 of 4 (0%) air samples from the HCU30 were positive, and 0 of 64 (0%) water samples and 0 of 50 (0%) air samples from the HCU40 were positive. We identified 4 relevant differences in HCU design compared to the 3T: air flow direction, location of cooling ventilators, continuous cooling of the water tank at 4°C, and an electronic alarm in the HCU40 reminding the user of the next disinfection cycle.

All infected patients were associated with a 3T HCU. The individual HCU design may explain the different risk of disseminating M. chimaera into the air of the operating room. These observations can help the construction of improved devices to ensure patient safety during cardiac surgery.

Infect Control Hosp Epidemiol 2018;834–840

Identify factors referred to as barriers and facilitators that can prevent or assist safe injection practices in ambulatory care settings to guide quality improvement.

In this mixed-methods study, we utilized observations and interviews.

This study was conducted at ambulatory clinics at a midwestern academic medical center from May through August 2017. Sites included a variety of clinical settings that performed intramuscular, intradermal, intravenous, or intra-articular injections.

Direct observations of injections and interviews of ambulatory care staff were conducted. An observation checklist was created, including standards of injection safety from nationally recognized guidelines. Interview questions were developed using the System Engineering Initiative for Patient Safety (SEIPS) model. Interviews were recorded, transcribed, and then coded by 2 investigators.

In total, 106 observations and 36 interviews were completed at 21 clinics. Injection safety standards with the lowest adherence included using needleless access devices to prepare injections (33%) and the proper use of multidose vials (<80%). Of 819 coded interview segments, 461 (56.3%) were considered facilitators of safe injection practices. The most commonly identified barriers were patient movement during administration, feeling rushed, and inadequate staffing. The most commonly identified facilitators were availability of supplies, experience in the practice area, and availability of safety needles and prefilled syringes.

Perceived barriers and facilitators to infection control elements of injection safety are interconnected with SEIPS elements of persons, organizations, technologies, tasks, and environment. Direct observations demonstrated that knowledge of safety injection standards does not necessarily translate to best practices and may not match self-reported data.

Infect Control Hosp Epidemiol 2018;39:841–848

We report the utility of whole-genome sequencing (WGS) conducted in a clinically relevant time frame (ie, sufficient for guiding management decision), in managing a Streptococcus pyogenes outbreak, and present a comparison of its performance with emm typing.

A 2,000-bed tertiary-care psychiatric hospital.

Active surveillance was conducted to identify new cases of S. pyogenes. WGS guided targeted epidemiological investigations, and infection control measures were implemented. Single-nucleotide polymorphism (SNP)–based genome phylogeny, emm typing, and multilocus sequence typing (MLST) were performed. We compared the ability of WGS and emm typing to correctly identify person-to-person transmission and to guide the management of the outbreak.

The study included 204 patients and 152 staff. We identified 35 patients and 2 staff members with S. pyogenes. WGS revealed polyclonal S. pyogenes infections with 3 genetically distinct phylogenetic clusters (C1–C3). Cluster C1 isolates were all emm type 4, sequence type 915 and had pairwise SNP differences of 0–5, which suggested recent person-to-person transmissions. Epidemiological investigation revealed that cluster C1 was mediated by dermal colonization and transmission of S. pyogenes in a male residential ward. Clusters C2 and C3 were genomically diverse, with pairwise SNP differences of 21–45 and 26–58, and emm 11 and mostly emm120, respectively. Clusters C2 and C3, which may have been considered person-to-person transmissions by emm typing, were shown by WGS to be unlikely by integrating pairwise SNP differences with epidemiology.

WGS had higher resolution than emm typing in identifying clusters with recent and ongoing person-to-person transmissions, which allowed implementation of targeted intervention to control the outbreak.

Infect Control Hosp Epidemiol 2018;852–860