To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
To compare clinical outcomes over time of inpatients with healthcare-associated coronavirus disease 2019 (HA-COVID-19) versus community-acquired COVID-19 (CA-COVID-19).
We conducted a multicenter, prospective observational cohort study of inpatients with COVID-19.
The study was conducted across 16 acute-care hospitals in Switzerland.
Participants and methods:
We compared HA-COVID-19 cases, defined as patients with a positive severe acute respiratory coronavirus virus 2 (SARS-CoV-2) test > 5 days after hospital admission, with hospitalized CA-COVID-19 cases, defined as those who tested positive within 5 days of admission. The composite primary outcome was patient transfer to an intensive care unit (ICU) or an intermediate care unit (IMCU) and/or all-cause in-hospital mortality. We used cause-specific Cox regression and Fine-Gray regression to model the time to the composite clinical outcome, adjusting for confounders and accounting for the competing event of discharge from hospital. We compared our results to those from a conventional approach using an adjusted logistic regression model where time-varying effects and competitive risk were ignored.
Between February 19, 2020, and December 31, 2020, we included 1,337 HA-COVID-19 cases and 9,068 CA-COVID-19 cases. HA-COVID-19 patients were significantly older: median, 80 (interquartile range [IQR], 71–87) versus median 70 (IQR, 57–80) (P < .001). A greater proportion of HA-COVID-19 patients had a Charlson comorbidity index ≥ 5 (79% vs 55%; P < .001) than did CA-COVID-19 patients. In time-varying analyses, between day 0 and 8, HA-COVID-19 cases had a decreased risk of death or ICU or IMCU transfer compared to CA-COVID-19 cases (cause-specific hazard ratio [csHR], 0.43; 95% confidence interval [CI], 0.33–0.56). In contrast, from day 8 to 30, HA-COVID-19 cases had an increased risk of death or ICU or IMCU transfer (csHR, 1.49; 95% CI, 1.20–1.85), with no significant effect on the rate of discharge (csHR, 0.83; 95% CI, 0.61–1.14). In the conventional logistic regression model, HA-COVID-19 was protective against transfer to an ICU or IMCU and/or all-cause in-hospital mortality (adjusted odds ratio [aOR], 0.79, 95% CI, 0.67–0.93).
The risk of adverse clinical outcomes for HA-COVID-19 cases increased substantially over time in hospital and exceeded that for CA-COVID-19. Using approaches that do not account for time-varying effects or competing events may not fully capture the true risk of HA-COVID-19 compared to CA-COVID-19.
The aim of this study was to quantify the time delay between screening and initiation of contact isolation for carriers of extended-spectrum beta-lactamase (ESBL)–producing Enterobacterales (ESBL-E).
This study was a secondary analysis of contact isolation periods in a cluster-randomized controlled trial that compared 2 strategies to control ESBL-E (trial no. ISRCTN57648070). Patients admitted to 20 non-ICU wards in Germany, the Netherlands, Spain, and Switzerland were screened for ESBL-E carriage on admission, weekly thereafter, and on discharge. Data collection included the day of sampling, the day the wards were notified of the result, and subsequent ESBL-E isolation days.
Between January 2014 and August 2016, 19,122 patients, with a length of stay ≥2 days were included. At least 1 culture was collected for 16,091 patients (84%), with a median duration between the admission day and the day of first sample collection of 2 days (interquartile range [IQR], 1–3). Moreover, 854 (41%) of all 2,078 ESBL-E carriers remained without isolation during their hospital stay. In total, 6,040 ESBL-E days (32% of all ESBL-E days) accrued for patients who were not isolated. Of 2,078 ESBL-E-carriers, 1,478 ESBL-E carriers (71%) had no previous history of ESBL-E carriage. Also, 697 (34%) were placed in contact isolation with a delay of 4 days (IQR, 2–5), accounting for 2,723 nonisolation days (15% of ESBL-E days).
Even with extensive surveillance screening, almost one-third of all ESBL-E days were nonisolation days. Limitations in routine culture-based ESBL-E detection impeded timely and exhaustive implementation of targeted contact isolation.
Hand hygiene is a simple, low-cost intervention that may lead to substantial population-level effects in suppressing acute respiratory infection epidemics. However, quantification of the efficacy of hand hygiene on respiratory infection in the community is lacking. We searched PubMed for randomised controlled trials on the effect of hand hygiene for reducing acute respiratory infections in the community published before 11 March 2021. We performed a meta-regression analysis using a Bayesian mixed-effects model. A total of 105 publications were identified, out of which six studies reported hand hygiene frequencies. Four studies were performed in household settings and two were in schools. The average number of handwashing events per day ranged from one to eight in the control arms, and four to 17 in the intervention arms. We estimated that a single hand hygiene event is associated with a 3% (80% credible interval (−1% to 7%)) decrease in the daily probability of an acute respiratory infection. Three of these six studies were potentially at high risk of bias because the primary outcome depended on self-reporting of upper respiratory tract symptoms. Well-designed trials with an emphasis on monitoring hand hygiene adherence are needed to confirm these findings.
An examination of all coronavirus disease 2019 (COVID-19) cases and patient movements in Geneva indicated important disease activity within the healthcare system since the beginning of the pandemic. We estimate that 4.3% of all COVID-19 cases were likely acquired within the healthcare system, contributing to 62% of the COVID-19–related deaths.
The dynamics of coronavirus disease 2019 (COVID-19) seroconversion of hospital employees are understudied. We measured the proportion of seroconverted employees and evaluated risk factors for seroconversion during the first pandemic wave.
In this prospective cohort study, we recruited Geneva University Hospitals employees and sampled them 3 times, every 3 weeks from March 30 to June 12, 2020. We measured the proportion of seroconverted employees and determined prevalence ratios of risk factors for seroconversion using multivariate mixed-effects Poisson regression models.
Overall, 3,421 participants (29% of all employees) were included, with 92% follow-up. The proportion of seroconverted employees increased from 4.4% (95% confidence interval [CI], 3.7%–5.1%) at baseline to 8.5% [(95% CI, 7.6%–9.5%) at the last visit. The proportions of seroconverted employees working in COVID-19 geriatrics and rehabilitation (G&R) wards (32.3%) and non–COVID-19 G&R wards (12.3%) were higher compared to office workers (4.9%) at the last visit. Only nursing assistants had a significantly higher risk of seroconversion compared to office workers (11.7% vs 4.9%; P = .006). Significant risk factors for seroconversion included the use of public transportation (adjusted prevalence ratio, 1.59; 95% CI, 1.25–2.03), known community exposure to severe acute respiratory coronavirus virus 2 (2.80; 95% CI, 2.22–3.54), working in a ward with a nosocomial COVID outbreak (2.93; 95% CI, 2.27–3.79), and working in a COVID-19 G&R ward (3.47; 95% CI, 2.45–4.91) or a non–COVID-19 G&R ward (1.96; 95% CI, 1.46–2.63). We observed an association between reported use of respirators and lower risk of seroconversion (0.73; 95% CI, 0.55–0.96).
Additional preventive measures should be implemented to protect employees in G&R wards. Randomized trials on the protective effect of respirators are urgently needed.
We evaluated the impact of a restriction of procalcitonin measurements on antibiotic use, length of stay, mortality, and cost in a Swiss tertiary-care hospital using interrupted time-series analysis. There was no significant change in level or slope for rates of antibiotic consumption, and costs decreased considerably, by ~54,488 CHF (US$55,714) per month.
Background:Candida auris is an emerging nosocomial fungal pathogen causing invasive illness and outbreaks worldwide. A major issue regarding C. auris is that it can be misidentified unless appropriate technology is used. We conducted a survey of available methods for identification of C. auris in 21 hospital laboratories in India regarding their protocols for prevention of C. auris infection. Methods: The survey was an adaptation of a similar survey conducted for the Connecticut Laboratory Response Network in 2017. We mailed the survey to 30 microbiologists and ID physicians, and 21 of them from 12 states responded. All respondents were from private acute-care and teaching hospitals. The responses were analyzed and compared to the Connecticut study. Results: Of 21 hospitals, 19 (90.5%) can identify C. auris in house. Also, 18 (85.7%) have identified C. auris in the past 18 months. Species level identification was done only for blood cultures in all hospitals. Only 5 (26%) laboratories speciated Candida spp isolated from other sites such as respiratory and urinary specimens. Automated systems were used like Vitek 2 in 16 (84.2%), Phoenix BD in 2(10.5%) and Microscan in 1(5.26%) laboratory. MALDI-TOF MS and PCR for identification were used in 2 laboratories. Antifungal susceptibility testing is done in-house in 19 (90.5%) laboratories. Only 10 (52.6%) responding hospitals from India had infection prevention protocols for C. auris, and 9 (47.4%) of them isolated patients. The major challenges for infection prevention with C. auris are absence of screening in high-risk patients (66.7%), misidentification by automated systems (84.2%), and inability to speciate from nonsterile sites underestimates the prevalence (100%). Conclusions: There is an urgent need to enhance the capacity of hospital laboratories to detect C. auris early, and to implement infection prevention measures. In both studies early detection is the key and as suggested by the US authors, challenges can be overcome through collaboration between hospitals and referral laboratories when resources are limited. This optimizes laboratory capacity and prevents global spread through colonized patients. The limitation of this study is that data from public hospitals are unknown and larger studies are needed.
The epidemiology of ESBL-producing Enterobacteriaceae (ESBL-PE) has been extensively studied in hospitals, but data on community transmission are scarce. We investigated ESBL-PE cocarriage and acquisition in households using a systematic literature review.
We conducted a systematic literature search to retrieve cross-sectional or cohort studies published between 1990 and 2018 evaluating cocarriage proportions and/or acquisition rates of ESBL-PE among household members, without language restriction. We excluded studies focusing on animal-to-human transmission or conducted in nonhousehold settings. The main outcomes were ESBL-PE cocarriage proportions and acquisition rates, stratified according to phenotypic or genotypic assessment of strain relatedness. Cocarriage proportions of clonally related ESBL-PE were transformed using the double-arcsine method and were pooled using a random-effects model. Potential biases were assessed manually.
We included 13 studies. Among 863 household members of ESBL-PE positive index cases, prevalence of ESBL-PE cocarriage ranged from 8% to 37%. Overall, 12% (95% confidence interval [CI], 8%–16%) of subjects had a clonally related strain. Those proportions were higher for Klebsiella pneumoniae (20%–25%) than for Escherichia coli (10%–20%). Acquisition rates of clonally related ESBL-PE among 180 initially ESBL-PE–free household members of a previously identified carrier ranged between 1.56 and 2.03 events per 1,000 person weeks of follow-up. We identified multiple sources of bias and high heterogeneity (I2, 70%) between studies.
ESBL-PE household cocarriage is frequent, suggesting intrafamilial acquisition. Further research is needed to evaluate the risk and control of ESBL-PE household transmission.
To assess the validity of multivariable models for predicting risk of surgical site infection (SSI) after colorectal surgery based on routinely collected data in national surveillance networks.
Retrospective analysis performed on 3 validation cohorts.
Colorectal surgery patients in Switzerland, France, and England, 2007–2017.
We determined calibration and discrimination (ie, area under the curve, AUC) of the COLA (contamination class, obesity, laparoscopy, American Society of Anesthesiologists [ASA]) multivariable risk model and the National Healthcare Safety Network (NHSN) multivariable risk model in each cohort. A new score was constructed based on multivariable analysis of the Swiss cohort following colorectal surgery, then based on colon and rectal surgery separately.
We included 40,813 patients who had undergone elective or emergency colorectal surgery to validate the COLA score, 45,216 patients to validate the NHSN colon and rectal surgery risk models, and 46,320 patients in the construction of a new predictive model. The COLA score’s predictive ability was poor, with AUC values of 0.64 (95% confidence interval [CI], 0.63–0.65), 0.62 (95% CI, 0.58–0.67), 0.60 (95% CI, 0.58–0.61) in the Swiss, French, and English cohorts, respectively. The NHSN colon-specific model (AUC, 0.61; 95% CI, 0.61–0.62) and the rectal surgery–specific model (AUC, 0.57; 95% CI, 0.53–0.61) showed limited predictive ability. The new predictive score showed poor predictive accuracy for colorectal surgery overall (AUC, 0.65; 95% CI, 0.64–0.66), for colon surgery (AUC, 0.65; 95% CI, 0.65–0.66), and for rectal surgery (AUC, 0.63; 95% CI, 0.60–0.66).
Models based on routinely collected data in SSI surveillance networks poorly predict individual risk of SSI following colorectal surgery. Further models that include other more predictive variables could be developed and validated.
To assess the prevalence of healthcare-associated infections (HAIs) in mainland China.
Systematic review and meta-analysis.
Adults and children from secondary and tertiary acute-care hospitals in mainland China.
We searched PubMed, the China National Knowledge Infrastructure, and Wan Fang for multicenter point-prevalence surveys of acute-care hospitals in mainland China from January 2006 to August 2016. All reports related to HAI, using a point-prevalence methodology and published either in English or Chinese were eligible.
In total, 3,021 publications were identified; 115 were eligible for quality assessment and data abstraction. The weighted HAI prevalence (95% confidence interval [CI]) overall, in general hospitals, children’s hospitals, maternal and child health hospitals, and oncology hospitals were 3.12% (95% CI, 2.94%–3.29%), 3.02% (95% CI, 2.79%–3.26%), 4.43% (95% CI, 3.39%–5.47%), 1.88% (95% CI, 1.47%–2.29%), and 3.96% (95% CI, 3.12%–4.79%), respectively. In general hospitals, prevalence was highest in adult intensive care units (26.07%; 95% CI, 23.03%–29.12%), followed by surgery (3.26%; 95% CI, 2.96%–3.57%), and internal medicine (3.06%; 95% CI, 2.67%–3.46%). Overall, lower respiratory tract infection was the most frequent HAI (24,185, 47.28%), followed by urinary tract infection (5,773, 11.29%) and upper respiratory tract infection (5,194, 10.15%). Gram-negative bacilli were the most frequently isolated pathogens, and Pseudomonas aeruginosa (3,395, 14.91%), and Escherichia coli (2,918, 12.82%) were the most common single microorganisms.
This study is the largest systematic review on the prevalence of HAI in mainland China. These results provide a benchmark for future PPSs and a reference for infection prevention and control strategies in mainland China.
Global discussions are ongoing on how to stimulate antibiotic research and development in order to provide patients with new antibiotics able to address the challenges of antimicrobial resistance. In this supplement, we present nine articles derived from the research performed as part of the Innovative Medicine Initiative-funded DRIVE-AB project and others. These publications provide new evidence and arguments in the debate around economic incentives to stimulate antibiotic innovation, including characteristics, implementation and governance.
This systematic literature review reveals that participating in a surgical site infection (SSI) surveillance network is associated with short-term reductions in SSI rates: relative risk [RR] for year 2, 0.80 (95% confidence interval [CI], 0.79–0.82); year 3 RR, 0.92 (95% CI, 0.90–0.94); year 4 RR, 0.98 (95% CI, 0.96–1.00).
Estimates of the excess length of stay (LOS) attributable to healthcare-associated infections (HAIs) in which total LOS of patients with and without HAIs are biased because of failure to account for the timing of infection. Alternate methods that appropriately treat HAI as a time-varying exposure are multistate models and cohort studies, which match regarding the time of infection. We examined the magnitude of this time-dependent bias in published studies that compared different methodological approaches.
We conducted a systematic review of the published literature to identify studies that report attributable LOS estimates using both total LOS (time-fixed) methods and either multistate models or matching patients with and without HAIs using the timing of infection.
Of the 7 studies that compared time-fixed methods to multistate models, conventional methods resulted in estimates of the LOS to HAIs that were, on average, 9.4 days longer or 238% greater than those generated using multistate models. Of the 5 studies that compared time-fixed methods to matching on timing of infection, conventional methods resulted in estimates of the LOS to HAIs that were, on average, 12.6 days longer or 139% greater than those generated by matching on timing of infection.
Our results suggest that estimates of the attributable LOS due to HAIs depend heavily on the methods used to generate those estimates. Overestimation of this effect can lead to incorrect assumptions of the likely cost savings from HAI prevention measures.
Infect. Control Hosp. Epidemiol. 2015;36(9):1089–1094
We performed a contingent valuation survey to elicit the opportunity cost of bed-days consumed by healthcare-associated infections in 11 European hospitals. The opportunity cost of a bed-day was significantly lower than the accounting cost; median values were €72 and €929, respectively (P < .001). Accounting methods overestimate the opportunity cost of bed-days.
Infect Control Hosp Epidemiol 2014;35(10):1294–1297
To test the hypothesis that methicillin-susceptible Staphylococcus aureus (MSSA) carriage may protect against nosocomial methicillin-resistant S. aureus (MRSA) acquisition by competing for colonization of the anterior nares.
Prospective cohort and nested case-control study.
Swiss university hospital.
All adult patients admitted to 14 wards of the general medicine division between April 1 and October 31, 2007.
Patients were screened for MRSA and MSSA carriage at admission to and discharge from the division. Associations between nosocomial MRSA acquisition and MSSA colonization at admission and other confounders were analyzed by univariable and multivariable analysis.
Of 898 patients included, 183 (20%) were treated with antibiotics. Nosocomial MRSA acquisition occurred in 70 (8%) of the patients (case patients); 828 (92%) of the patients (control subjects) were free of MRSA colonization at discharge. MSSA carriage at admission was 20% and 21% for case patients and control subjects, respectively. After adjustment by multivariate logistic regression, no association was observed between MSSA colonization at admission and nosocomial MRSA acquisition (adjusted odds ratio [aOR], 1.2 [95% confidence interval (CI), 0.6–2.3]). By contrast, 4 independent predictors of nosocomial MRSA acquisition were identified: older age (aOR per 1-year increment, 1.05 [95% CI, 1.02–1.08]); increased length of stay (aOR per 1-day increment, 1.05 [95% CI, 1.02–1.09]); increased nursing workload index (aOR per 1-point increment, 1.02 [95% CI, 1.01–1.04]); and previous treatment with macrolides (aOR, 5.6 [95% CI, 1.8–17.7]).
Endogenous MSSA colonization does not appear to protect against nosocomial MRSA acquisition in a population of medical patients without frequent antibiotic exposure.
Determine the prevalence of extended-spectrum β-lactamase (ESBL)–producing Enterobacteriaceae (ESBL-PE) contamination of food and colonization of food handlers in a hospital kitchen and compare retrieved ESBL-PE strains with patient isolates.
A 2,200-bed tertiary care university hospital in Switzerland.
Raw and prepared food samples were obtained from the hospital kitchen, with a comparator group from local supermarkets. Fecal samples collected from food handlers and selectively pre-enriched homogenized food samples were inoculated onto selective chromogenic media. Phenotypic confirmation of ESBL production was performed using the double disk method. Representative ESBL-PE were characterized using polymerase chain reaction (PCR) and sequencing for blaCTX-M, blaSHV, and blaTEM genes, and Escherichia coli strains were typed using phylotyping, repetitive element palindromic PCR, and multilocus sequence typing. Meat samples were screened for antibiotic residues using liquid chromatography time-of-flight mass spectrometry.
Sixty (92%) of the raw chicken samples were ESBL-PE positive, including 30 (86%) of the hospital samples and all supermarket samples. No egg, beef, rabbit, or cooked chicken samples were ESBL-PE positive. No antibiotic residues were detected. Six (6.5%) of 93 food handlers were ESBL-PE carriers. ESBL-PE strains from chicken meat more commonly possessed blaCTX-M-1 and blaCTX-M-2, whereas blaCTX-M-14and blaCTX-M-15 were predominant among strains of human origin. There was partial overlap in the sequence type of E. coli strains of chicken and human origin. No E. coli ST131 strains or blaCTX-M-15 genes were isolated from meat.
Although there is significant ESBL-PE contamination of delivered chicken meat, current preventive strategies minimize risks to food handlers, hospital staff, and patients.
To obtain an unbiased estimate of the excess hospital length of stay (LOS) and cost attributable to extended-spectrum β-lactamase (ESBL) positivity in bloodstream infections (BSIs) due to Enterobacteriaceae.
Retrospective cohort study.
A 2,200-bed academic medical center in Geneva, Switzerland.
Patients admitted during 2009.
We used multistate modeling and Cox proportional hazards models to determine the excess LOS and adjusted end-of-LOS hazard ratio (HR) for ESBL-positive and ESBL-negative BSI. We estimated economic burden as the product of excess LOS and average bed-day cost. Patient-level accounting data provided a complementary analysis of economic burden. A predictive model was fitted to national surveillance data.
Thirty ESBL-positive and 96 ESBL-negative BSI cases were included. The excess LOS attributable to ESBL-positive and ESBL-negative BSI was 9.4 (95% confidence interval [CI], 0.4–18.4) and 2.6 (95% CI, 0.7–5.9) days, respectively. ESBL positivity was therefore associated with 6.8 excess days and CHF 9,473 per BSI. The adjusted end-of-LOS HRs for ESBL-positive and ESBL-negative BSI were 0.62 (95% CI, 0.43–0.89) and 0.90 (95% CI, 0.74–1.10), respectively. After reimbursement, the average financial loss per acute care episode in ESBL-positive BSI, ESBL-negative BSI, and control cohorts was CHF 48,674, 48,131, and 13,532, respectively. Our predictive model estimated that the nationwide cost of third-generation cephalosporin resistance would increase from CHF 2,084,000 in 2010 to CHF 3,526,000 in 2015.
This is the first hospital-wide analysis of excess LOS attributable to ESBL positivity determined using multistate modeling to avoid time-dependent bias. These results may inform health-economic evaluations of interventions targeting ESBL control.