Objective: The preventable proportion of healthcare-associated infections (HAIs) may decrease over time as standards of care improve. We aimed to assess the proportion of HAIs prevented by multifaceted infection control interventions in different economic settings.Methods: In this systematic review and meta-analysis, we searched OVID Medline, EMBASE, CINAHL, PubMed, and The Cochrane Library for studies published between 2005 and 2016 assessing multifaceted interventions to reduce catheter-associated urinary tract infections (CAUTIs), central-line–associated bloodstream infections (CLABSIs), surgical site infections (SSIs), ventilator-associated pneumonia (VAP), and hospital-acquired pneumonia not associated with mechanical ventilation (HAP) in acute-care or long-term care settings. For studies reporting raw rates, we extracted data and calculated the natural log of the risk ratio and variance to obtain pooled risk ratio estimates.Results: Of the 5,226 articles identified by our search, 144 studies were included in the final analysis. Pooled incidence rate ratios associated with multifaceted interventions were 0.543 (95% confidence interval [CI], 0.445–0.662) for CAUTI, 0.459 (95% CI, 0.381–0.554) for CLABSI, and 0.553 (95% CI, 0.465–0.657) for VAP. The pooled rate ratio was 0.461 (95% CI, 0.389–0.546) for interventions aiming at SSI reduction, and for VAP reduction initiatives, the pooled rate ratios were 0.611 (95% CI, 0.414–0.900) for before-and-after studies and 0.509 (95% CI, 0.277–0.937) for randomized controlled trials. Reductions in infection rates were independent of the economic status of the study country. The risk of bias was high in 143 of 144 studies (99.3%).Conclusions: Published evidence suggests a sustained potential for the significant reduction of HAI rates in the range of 35%–55% associated with multifaceted interventions irrespective of a country’s income level.

Infections caused by carbapenemase-producing, multidrug-resistant (MDR), or extensively drug-resistant (XDR) Gram-negative bacteria constitute a major therapeutic challenge. Whether combination antibiotic therapy is superior to monotherapy remains unknown. In this systematic review and meta-analysis OVID MEDLINE, EMBASE, PubMed, The Cochrane Library, and Scopus databases were searched for randomized controlled trials (RCTs) and observational studies published by December 2016 comparing mono- with combination antibiotic therapy for infections with carbapenemase-producing, MDR, or XDR Gram-negative bacteria. Mortality and clinical cure rates served as primary and secondary outcome measures, respectively. Of 8847 initially identified studies, 53 studies – covering pneumonia (n = 10 studies), blood stream (n = 15), osteoarticular (n = 1), and mixed infections (n = 27) - were included. 41% (n = 1848) of patients underwent monotherapy, and 59% (n = 2666) combination therapy. In case series/cohort studies (n = 45) mortality was lower with combination- vs. monotherapy (RR 0.83, CI 0.73–0.93, p = 0.002, I² = 24%). Subgroup analysis revealed lower mortality with combination therapy with at least two in-vitro active antibiotics, in blood stream infections, and carbapenemase-producing Enterobacteriaceae. No mortality difference was seen in case-control studies (n = 6) and RCTs (n = 2). Cure rates did not differ regardless of study type. The two included RCTs had a high and unknown risk of bias, respectively. 16.7% (1/6) of case-control studies and 37.8% (17/45) of cases series/cohort studies were of good quality, whereas quality was poor in the remaining studies. In conclusion, combination antimicrobial therapy of multidrug-resistant Gram-negative bacteria appears to be superior to monotherapy with regard to mortality.

HIV‐infected women are at increased risk of cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC), but it has been difficult to disentangle the influences of heavy exposure to HPV infection, inadequate screening and immunodeficiency. A case‐control study including 364 CIN2/3 and 20 ICC cases matched to 1,147 controls was nested in the Swiss HIV Cohort Study (1985–2013). CIN2/3 risk was significantly associated with low CD4+ cell counts, whether measured as nadir [odds ratio (OR) per 100‐cell/μL decrease = 1.15, 95% CI: 1.08, 1.22], or at CIN2/3 diagnosis (1.10, 95% CI: 1.04, 1.16). An association was evident even for nadir CD4+ 200–349 versus ≥350 cells/μL (OR = 1.57, 95% CI: 1.09, 2.25). After adjustment for nadir CD4+, a protective effect of >2‐year cART use was seen against CIN2/3 (OR versus never cART use = 0.64, 95% CI: 0.42, 0.98). Despite low study power, similar associations were seen for ICC, notably with nadir CD4+ (OR for 50 vs. >350 cells/μL= 11.10, 95% CI: 1.24, 100). HPV16‐L1 antibodies were significantly associated with CIN2/3, but HPV16‐E6 antibodies were nearly exclusively detected in ICC. In conclusion, worsening immunodeficiency, even at only moderately decreased CD4+ cell counts, is a significant risk factor for CIN2/3 and cervical cancer.

Objective: The transfer of pathogens may spread antimicrobial resistance and lead to healthcare-acquired infections. We performed a systematic literature review to generate estimates of pathogen transfer in relation to healthcare provider (HCP) activities.Methods: For this systematic review and meta-analysis, Medline/Ovid, EMBASE, and the Cochrane Library were searched for studies published before July 7, 2017. We reviewed the literature, examining transfer of pathogens associated with HCP activities. We included studies that (1) quantified transfer of pathogens from a defined origin to a defined destination surface; (2) reported a microbiological sampling technique; and (3) described the associated activity leading to transfer. For studies reporting transfer frequencies, we extracted data and calculated the estimated proportion using Freeman-Tukey double arcsine transformation and the DerSimonian-Laird random-effects model.Results: Of 13,121 identified articles, 32 were included. Most articles (n=27, 84%) examined transfer from patients and their environment to HCP hands, gloves, and gowns, with an estimated proportion for transfer frequency of 33% (95% confidence interval [CI], 12%–57%), 30% (95% CI, 23%–38%) and 10% (95% CI, 6%–14%), respectively. Other articles addressed transfer involving the hospital environment and medical devices. Risk factor analyses in 12 studies suggested higher transfer frequencies after contact with moist body sites (n=7), longer duration of care (n=5), and care of patients with an invasive device (n=3).Conclusions: Recognizing the heterogeneity in study designs, the available evidence suggests that pathogen transfer to HCPs occurs frequently. More systematic research is urgently warranted to support targeted and economic prevention policies and interventions.

Background: A multitude of definitions determining multidrug resistance (MDR) of Gram-negative organisms exist worldwide. The definitions differ depending on their purpose and on the issueing country or organization. The MDR definitions of the European Centre for Disease Prevention and Control (ECDC) were primarily chosen to harmonize epidemiological surveillance. The German Commission of Hospital Hygiene and Infection Prevention (KRINKO) issued a national guideline which is mainly used to guide infection prevention and control (IPC) measures. The Swiss University Hospital Zurich (UHZ) – in absentia of national guidelines – developed its own definition for IPC purposes. In this study we aimed to determine the effects of different definitions of multidrug-resistance on rates of Gram-negative multidrug-resistant organisms (GN-MDRO). Methods: MDR definitions of the ECDC, the German KRINKO and the Swiss University Hospital Zurich were applied on a dataset comprising isolates of Escherichia coli, Klebsiella pneumoniae, Enterobacter sp., Pseudomonas aeruginosa, and Acinetobacter baumannii complex. Rates of GN-MDRO were compared and the percentage of patients with a GN-MDRO was calculated. Results: In total 11′407 isolates from a 35 month period were included. For Enterobacterales and P. aeruginosa, highest MDR-rates resulted from applying the ‘ECDC-MDR’ definition. ‘ECDC-MDR’ rates were up to four times higher compared to ‘KRINKO-3/4MRGN’ rates, and up to six times higher compared to UHZ rates. Lowest rates were observed when applying the ‘KRINKO-4MRGN’ definitions. Comparing the ‘KRINKO-3/4MRGN’ with the UHZ definitions did not show uniform trends, but yielded higher rates for E. coli and lower rates for P. aeruginosa. On the patient level, the percentages of GN-MDRO carriers were 2.1, 5.5, 6.6, and 18.2% when applying the ‘KRINKO-4MRGN’, ‘UHZ-MDR’, ‘KRINKO-3/4MRGN’, and the ‘ECDC-MDR’ definition, respectively. Conclusions: Different MDR-definitions lead to considerable variation in rates of GN-MDRO. Differences arise from the number of antibiotic categories required to be resistant, the categories and drugs considered relevant, and the antibiotic panel tested. MDR definitions should be chosen carefully depending on their purpose and local resistance rates, as definitions guiding isolation precautions have direct effects on costs and patient care.

We studied whether the change in antibiotic susceptibility testing (AST) guidelines from CLSI to EUCAST influenced cumulative antibiograms in a tertiary care hospital in Switzerland. Antibiotic susceptibilities of non-duplicate isolates collected within a one-year period before (period A) and after (period B) changing AST interpretation from CLSI 2009 to EUCAST 1.3 (2011) guidelines were analysed. In addition, period B isolates were reinterpreted according to the CLSI 2009, CLSI 2013 and EUCAST 3.1 (2013) guidelines. The majority of species/drug combinations showed no differences in susceptibility rates comparing periods A and B. However, in some gram-negative bacilli, decreased susceptibility rates were observed when comparing CLSI 2009 with EUCAST 1.3 within period B: Escherichia coli / cefepime, 95.8% (CLSI 2009) vs. 93.1% (EUCAST 1.3), P=0.005; Enterobacter cloacae / cefepime, 97.0 (CLSI 2009) vs. 90.5% (EUCAST 1.3), P=0.012; Pseudomonas aeruginosa / meropenem, 88.1% (CLSI 2009) vs. 78.3% (EUCAST 1.3), P=0.002. These differences were still evident when comparing susceptibility rates according to the CLSI 2013 guideline with EUCAST 3.1 guideline. For P. aeruginosa and imipenem, a trend towards a lower antibiotic susceptibility rate in ICUs compared to general wards turned into a significant difference after the change to EUCAST: 87.9% vs. 79.8%, P=0.08 (CLSI 2009) and 86.3% vs. 76.8%, P=0.048 (EUCAST 1.3). The change of AST guidelines from CLSI to EUCAST led to a clinically relevant decrease of susceptibility rates in cumulative antibiograms for defined species/drug combinations, particularly in those with considerable differences in clinical susceptibility breakpoints between the two guidelines.