Infection Control & Hospital Epidemiology
Methods Setting and study design
This study was performed at the University Hospital Basel, a tertiary-care center in Switzerland with 855 beds and 35,000 admissions per year, including ∼5,300 admissions to the surgical and medical ICUs. From November 2014 to August 2015, all patients admitted to
the surgical and medical ICUs needing mechanical ventilation and expected to require intensive care for >48 hours were routinely screened on admission for ESBL-PE carriage by a single rectal swab. Routine screening of this patient population is outlined in our institutional guidelines and is conducted for surveillance pur- poses. Automated alerts were set in the computer-based monitor- ing and prescribing software (METAVISION by iMDSoft, Tel Aviv, Israel) and remained active until swabs were marked as per- formed by the ICU nurses. Screening results were available to the treating physicians through the laboratory information system. This study was approved by the local ethics committee
(Ethikkommission Nordwest- und Zentralschweiz, EKNZ BASEC 2016-00704), and informed consent was waived.
Microbiological analyses
Rectal swabs were collected within the first 2 days of ICU admis- sion. Standard culture methods using chromogenic screening agar plates (chromID ESBL, bioMérieux, Marcy-l`Etoile, France) were applied for detection of ESBL-PE. Species identification was con- ducted with matrix-assisted laser desorption/ionization time-of- flight mass spectroscopy (MALDI-TOF MS; Bruker Daltonics, Bremen, Germany). Susceptibility testing was performed using the Vitek 2 system (bioMérieux, Durham, NC). ESBL-PE was con- firmed using Etest strips (bioMérieux, Marcy-l`Etoile, France) containing cefotaxime, ceftazidime, and cefepime, each tested with and without clavulanic acid. Unclear results were further evaluated using the Easyplex Superbug CPE panel including CTX-M1 and CTX-M9 genes. If these genes were absent, the result was consid- ered negative, based on our local epidemiology.15
Clinical data
Pertinent data (baseline characteristics and clinical features) were collected retrospectively by reviewing the electronic patient records. Immunosuppression was defined as high-dose corticoste- roids (prednisone equivalent of ≥1 mg/kg body weight in the pre- vious 7 days) and all types of agents to prevent graft rejection in solid organ or human stem cell or bone marrow transplantation and to treat autoimmune diseases used in the last 3 months. Other data collected included (1) known colonization with multi- drug-resistant bacteria (ie, methicillin-resistant Staphylococcus aureus [MRSA], ESBLs, vancomycin-resistant Enterococci, other multidrug-resistant[MDR] gram-negative bacteria as defined else- where16), (2) antibiotic therapy since hospital admission prior to receipt of the screening result, (3) first course of empiric antibiotic therapy after receipt of the screening result, and (4) carbapenem exposure (days) during ICU stay. We also collected data regarding (5) causative pathogen and infection focus of the first empirically treated infection after receipt of the screening result, (6) presence of septic shock (defined as an increase in serum lactate level and new or increased need for vasopressors) at initiation of a first empiric treatment regimen after receipt of the screening result, and (7) death during hospital stay (ie, overall, attributable to any infection, or attributable to infection caused by ESBL-PE).
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Infections were defined according to the National Healthcare Safety Network Patient Safety Component Manual by the Centers for Disease Control and Prevention.17
Outcome measures
The primary outcomes were colonization and infection with ESBL- PE. Occurrence of any infection during ICU stay, exposure to carbapenems, length of ICU and hospital stay in survivors, as well as death (ie, overall or attributable to infection) were considered as secondary outcomes.
Statistics
Patients were categorized as colonized and not colonized with ESBL-PE. Comparisons were undertaken to identify risk factors for ESBL-PE colonization. Continuous variables were summarized as medians and interquartile ranges and were compared using the Mann-Whitney U test. Categorical variables were summarized as counts, and proportions and differences were assessed using χ2 tests or the Fisher exact test when appropriate. Hazard ratios (HRs) were calculated to assess the risk of any infection, infection with ESBL-PE, exposure to carbapenems, and death. Fine and Gray competing risk regression analyses were used to account for the competing risks of development of infection, as well as receipt of carbapenems and death during hospital stay, where appropriate.18 Time to development of ESBL-PE infection and to receipt of car-
bapenems in association with ESBL-PE colonization were described using a cumulative incidence function plot.19Two-sidedPvalues<.05 were considered significant. Analyses were performed using STATA version 14.0 statistical software (StataCorp, College Station, TX).
Results
Overall, 302 patients were screened for ESBL-PE carriage and were included in the study. Screening was performed within 2 days of ICU admission (median, 1 day; interquartile range [IQR], 1–2 days). Table 1 summarizes their baseline characteristics. Of the included 302 patients, 24 (8.0%) were colonized with ESBL-PE (22 with ESBL Escherichia coli, 1 with ESBL Klebsiella pneumoniae, and 1 with ESBL Providentia stuartii) on ICU admission. The only factor associated with ESBL colonization was known colonization with multidrug-resistant gram-negative pathogens (Table 2). In total, 120 patients (39.4%) were diagnosed with an infection
after the availability of the ESBL-PE screening; among them, 10 (3.3%) developed septic shock. In 66 of these 120 patients (55%), infection was related to a pulmonary source. Patients with ESBL-PE colonization were not at increased risk for developing any infection (HR, 1.21; 95% CI, 0.64–2.28; P=.567) or septic shock (0% vs 3.6%; P=1.000). Infections with ESBL-PE occurred in 4 patients, of whom 3 (75%) had been identified as ESBL-PE- carriers on admission. ESBL-PE colonization on admission was associated with subsequent ESBL-PE infection (HR, 25.52; 95% CI, 2.40–271.41; P=.007) (Fig. 1). In 120 patients (39.9%), empiric antibiotic treatment was
started after the screening result was obtained. In 39 patients (32.5% of those receiving an empiric treatment) empiric therapy included a carbapenem. Colonization with ESBL-PE was associ- ated with increased exposure to carbapenems (HR, 2.42; 95% CI, 1.01–5.79; P=.047) (Fig. 2), whereas the duration of carbape- nem exposure (median 7, days [IQR, 3–8 days] vs median, 6 days [IQR, 3–9 days]; P=.983) did not differ between patients colonized and not colonized with ESBL-PE.
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