Nosocomial Infections During Extracorporeal Membrane Oxygenation in Neonatal, Pediatric, and Adult Patients: A Comprehensive Narrative Review.

OBJECTIVES: Extracorporeal membrane oxygenation is increasingly used in critically ill patients with refractory cardiopulmonary failure. Nosocomial infection acquired during extracorporeal membrane oxygenation represents one of the most frequent complications but the available evidence on the risk of infection and its association with outcomes has not been comprehensively analyzed. We performed a narrative review examining the epidemiology of nosocomial infection during extracorporeal membrane oxygenation, association with clinical outcomes, and preventive strategies. DATA SOURCES: We searched PubMed, Web of Science, EMBASE, and the Cochrane Library between 1972 and June 2018. STUDY SELECTION: We included any article which detailed nosocomial infection during extracorporeal membrane oxygenation. Articles were excluded if they were not written in English, detailed extracorporeal membrane oxygenation use for infections acquired prior to extracorporeal membrane oxygenation, or used other forms of extracorporeal support such as ventricular assist devices. DATA EXTRACTION: Two reviewers independently assessed eligibility and extracted data. We screened 984 abstracts and included 59 articles in the final review. DATA SYNTHESIS: The reported risk of nosocomial infection among patients receiving extracorporeal membrane oxygenation ranged from 3.5% to 64% per extracorporeal membrane oxygenation run, while the incidence of infection ranged from 10.1 to 116.2/1,000 extracorporeal membrane oxygenation days. Nosocomial infections during extracorporeal membrane oxygenation were consistently associated with longer duration of extracorporeal membrane oxygenation and, in several large multicenter studies, with increased mortality. Risk factors for nosocomial infection included duration of extracorporeal membrane oxygenation, mechanical and hemorrhagic complications on extracorporeal membrane oxygenation, and use of venoarterial and central extracorporeal membrane oxygenation. Biomarkers had low specificity for infection in this population. Few studies examined strategies on how to prevent nosocomial infection on extracorporeal membrane oxygenation. CONCLUSIONS: Nosocomial infections in extracorporeal membrane oxygenation patients are common and associated with worse outcomes. There is substantial variation in the rates of reported infection, and thus, it is possible that some may be preventable. The evidence for current diagnostic, preventive, and therapeutic strategies for infection during extracorporeal membrane oxygenation is limited and requires further investigation.

Bias and inference from misspecified mixed-effect models in stepped wedge trial analysis.

Many stepped wedge trials (SWTs) are analysed by using a mixed-effect model with a random intercept and fixed effects for the intervention and time periods (referred to here as the standard model). However, it is not known whether this model is robust to misspecification. We simulated SWTs with three groups of clusters and two time periods; one group received the intervention during the first period and two groups in the second period. We simulated period and intervention effects that were either common-to-all or varied-between clusters. Data were analysed with the standard model or with additional random effects for period effect or intervention effect. In a second simulation study, we explored the weight given to within-cluster comparisons by simulating a larger intervention effect in the group of the trial that experienced both the control and intervention conditions and applying the three analysis models described previously. Across 500 simulations, we computed bias and confidence interval coverage of the estimated intervention effect. We found up to 50% bias in intervention effect estimates when period or intervention effects varied between clusters and were treated as fixed effects in the analysis. All misspecified models showed undercoverage of 95% confidence intervals, particularly the standard model. A large weight was given to within-cluster comparisons in the standard model. In the SWTs simulated here, mixed-effect models were highly sensitive to departures from the model assumptions, which can be explained by the high dependence on within-cluster comparisons. Trialists should consider including a random effect for time period in their SWT analysis model. © 2017 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.

Assessing the impact of a cleaning programme on environmental hygiene in labour and neonatal wards: an exploratory study in The Gambia.

BACKGROUND: Effective surface cleaning in hospitals is crucial to prevent the transmission of pathogens. However, hospitals in low- and middle-income countries face cleaning challenges due to limited resources and inadequate training. METHODS: We assessed the effectiveness of a modified TEACH CLEAN programme for trainers in reducing surface microbiological contamination in the newborn unit of a tertiary referral hospital in The Gambia. We utilised a quasi-experimental design and compared data against those from the labour ward. Direct observations of cleaning practices and key informant interviews were also conducted to clarify the programme's impact. RESULTS: Between July and September 2021 (pre-intervention) and October and December 2021 (post-intervention), weekly surface sampling was performed in the newborn unit and labour ward. The training package was delivered in October 2021, after which their surface microbiological contamination deteriorated in both clinical settings. While some cleaning standards improved, critical aspects such as using fresh cleaning cloths and the one-swipe method did not. Interviews with senior departmental and hospital management staff revealed ongoing challenges in the health system that hindered the ability to improve cleaning practices, including COVID-19, understaffing, disruptions to water supply and shortages of cleaning materials. CONCLUSIONS: Keeping a hospital clean is fundamental to good care, but training hospital cleaning staff in this low-income country neonatal unit failed to reduce surface contamination levels. Further qualitative investigation revealed multiple external factors that challenged any possible impact of the cleaning programme. Further work is needed to address barriers to hospital cleaning in low-income hospitals.

Correction: Postnatal infection surveillance by telephone in Dar es Salaam, Tanzania: An observational cohort study.

[This corrects the article DOI: 10.1371/journal.pone.0254131.].

Why local antibiotic resistance data matters - Informing empiric prescribing through local data collation, app design and engagement in Zambia.

BACKGROUND: Control of antimicrobial resistance (AMR) relies on local knowledge and local intervention implementation. Effective antibiotic stewardship requires locally-suitable prescribing guidelines. We aimed to use a novel digital tool (the ZARIApp) and a participatory approach to help develop locally-relevant empiric antibiotic prescribing guidelines for two hospitals in Lusaka, Zambia. METHODS: We produced an AMR report using samples collected locally and routinely from adults within the prior two years (April 2020 - April 2022). We developed the ZARIApp, which provides prescribing recommendations based on local resistance data and antibiotic prescribing practices. We used qualitative evaluation of focus group discussions among healthcare professionals to assess the feasibility and acceptability of using the ZARIApp and identify the barriers to and enablers of this stewardship approach. RESULTS: Resistance prevalence was high for many key pathogens: for example, 73% of 41 Escherichia coli isolates were resistant to ceftriaxone. We identified that high resistance rates were likely due to low levels of requesting and processing of microbiology samples from patients leading to insufficient and unrepresentative microbiology data. This emerged as the major barrier to generating locally-relevant guidelines. Through active stakeholder engagement, we modified the ZARIApp to better support users to generate empirical antibiotic guidelines within this context of unrepresentative microbiology data. Qualitative evaluation of focus group discussions suggested that the resulting ZARIApp was useful and easy to use. New antibiotic guidelines for key syndromes are now in place in the two study hospitals, but these have substantial residual uncertainty. CONCLUSIONS: Tools such as the free online ZARIApp can empower local settings to better understand and optimise how sampling and prescribing can help to improve patient care and reduce future AMR. However, the usability of the ZARIApp is severely limited by unrepresentative microbiology data; improved routine microbiology surveillance is vitally needed.

Circumstances for treatment and control of invasive Enterobacterales infections in eight hospitals across sub-Saharan Africa: a cross-sectional study.

Background: Bloodstream infections caused by Enterobacterales show high frequency of antimicrobial resistance (AMR) in many Low- and Middle-Income Countries. We aimed to describe the variation in circumstances for management of such resistant infections in a group of African public-sector hospitals participating in a major research study. Methods: We gathered data from eight hospitals across sub-Saharan Africa to describe hospital services, infection prevention and antibiotic stewardship activities, using two WHO-generated tools. We collected monthly cross-sectional data on availability of antibiotics in the hospital pharmacies for bloodstream infections caused by Enterobacterales. We compared the availability of these antibiotics to actual patient-level use of antibiotics in confirmed Enterobacterales bloodstream infections (BSI). Results: Hospital circumstances for institutional management of resistant BSI varied markedly. This included self-evaluated infection prevention level (WHO-IPCAF score: median 428, range 155 to 687.5) and antibiotic stewardship activities (WHO stewardship toolkit questions: median 14.5, range 2 to 23). These results did not correlate with national income levels. Across all sites, ceftriaxone and ciprofloxacin were the most consistently available antibiotic agents, followed by amoxicillin, co-amoxiclav, gentamicin and co-trimoxazole. There was substantial variation in the availability of some antibiotics, especially carbapenems, amikacin and piperacillin-tazobactam with degree of access linked to national income level. Investigators described out-of-pocket payments for access to additional antibiotics at 7/8 sites. The in-pharmacy availability of antibiotics correlated well with actual use of antibiotics for treating BSI patients. Conclusions: There was wide variation between these African hospitals for a range of important circumstances relating to treatment and control of severe bacterial infections, though these did not all correspond to national income level. For most antibiotics, patient-level use reflected in-hospital drug availability, suggesting external antibiotics supply was infrequent. Antimicrobial resistant bacterial infections could plausibly show different clinical impacts across sub-Saharan Africa due to this contextual variation.

Mortality associated with third-generation cephalosporin resistance in Enterobacterales bloodstream infections at eight sub-Saharan African hospitals (MBIRA): a prospective cohort study.

BACKGROUND: Bacteria of the order Enterobacterales are common pathogens causing bloodstream infections in sub-Saharan Africa and are frequently resistant to third-generation cephalosporin antibiotics. Although third-generation cephalosporin resistance is believed to lead to adverse outcomes, this relationship is difficult to quantify and has rarely been studied in this region. We aimed to measure the effects associated with resistance to third-generation cephalosporins in hospitalised patients with Enterobacterales bloodstream infection in Africa. METHODS: We conducted a prospective, matched, parallel cohort study at eight hospitals across sub-Saharan Africa. We recruited consecutive patients of all age groups with laboratory-confirmed Enterobacterales bloodstream infection and matched them to at least one patient without bloodstream infection on the basis of age group, hospital ward, and admission date. Date of infection onset (and enrolment) was defined as the day of blood sample collection for culturing. Patients infected with bacteria with a cefotaxime minimum inhibitory concentration of 1 mg/L or lower were included in the third-generation cephalosporin-susceptible (3GC-S) cohort, and the remainder were included in the third-generation cephalosporin-resistant (3GC-R) cohort. The primary outcomes were in-hospital death and death within 30 days of enrolment. We used adjusted multivariable regression models to first compare patients with bloodstream infection against matched patients within the 3GC-S and 3GC-R cohorts, then compared estimates between cohorts. FINDINGS: Between Nov 1, 2020, and Jan 31, 2022, we recruited 878 patients with Enterobacterales bloodstream infection (221 [25·2%] to the 3GC-S cohort and 657 [74·8%] to the 3GC-R cohort) and 1634 matched patients (420 [25·7%] and 1214 [74·3%], respectively). 502 (57·2%) bloodstream infections occurred in neonates and infants (age 0-364 days). Klebsiella pneumoniae (393 [44·8%] infections) and Escherichia coli (224 [25·5%] infections) were the most common Enterobacterales species identified. The proportion of patients who died in hospital was higher in patients with bloodstream infection than in matched controls in the 3GC-S cohort (62 [28·1%] of 221 vs 22 [5·2%] of 420; cause-specific hazard ratio 6·79 [95% CI 4·06-11·37] from Cox model) and the 3GC-R cohort (244 [37·1%] of 657 vs 115 [9·5%] of 1214; 5·01 [3·96-6·32]). The ratio of these cause-specific hazard ratios showed no significant difference in risk of in-hospital death in the 3GC-R cohort versus the 3GC-S cohort (0·74 [0·42-1·30]). The ratio of relative risk of death within 30 days (0·82 [95% CI 0·53-1·27]) also indicated no difference between the cohorts. INTERPRETATION: Patients with bloodstream infections with Enterobacterales bacteria either resistant or susceptible to third-generation cephalosporins had increased mortality compared with uninfected matched patients, with no differential effect related to third-generation cephalosporin-resistance status. However, this finding does not account for time to appropriate antibiotic treatment, which remains clinically important to optimise. Measures to prevent transmission of Enterobacterales could reduce bloodstream infection-associated mortality from both drug-resistant and drug-susceptible bacterial strains in Africa. FUNDING: Bill & Melinda Gates Foundation.

Exploring the views of infection consultants in England on a novel delinked funding model for antimicrobials: the SMASH study.

Objectives: A novel 'subscription-type' funding model was launched in England in July 2022 for ceftazidime/avibactam and cefiderocol. We explored the views of infection consultants on important aspects of the delinked antimicrobial funding model. Methods: An online survey was sent to all infection consultants in NHS acute hospitals in England. Results: The response rate was 31.2% (235/753). Most consultants agreed the model is a welcome development (69.8%, 164/235), will improve treatment of drug-resistant infections (68.5%, 161/235) and will stimulate research and development of new antimicrobials (57.9%, 136/235). Consultants disagreed that the model would lead to reduced carbapenem use and reported increased use of cefiderocol post-implementation. The presence of an antimicrobial pharmacy team, requirement for preauthorization by infection specialists, antimicrobial stewardship ward rounds and education of infection specialists were considered the most effective antimicrobial stewardship interventions. Under the new model, 42.1% (99/235) of consultants would use these antimicrobials empirically, if risk factors for antimicrobial resistance were present (previous infection, colonization, treatment failure with carbapenems, ward outbreak, recent admission to a high-prevalence setting).Significantly higher insurance and diversity values were given to model antimicrobials compared with established treatments for carbapenem-resistant infections, while meropenem recorded the highest enablement value. Use of both 'subscription-type' model drugs for a wide range of infection sites was reported. Respondents prioritized ceftazidime/avibactam for infections by bacteria producing OXA-48 and KPC and cefiderocol for those producing MBLs and infections with Stenotrophomonas maltophilia, Acinetobacter spp. and Burkholderia cepacia. Conclusions: The 'subscription-type' model was viewed favourably by infection consultants in England.

Risk and causes of paediatric hospital-acquired bacteraemia in Kilifi District Hospital, Kenya: a prospective cohort study.

BACKGROUND: In sub-Saharan Africa, community-acquired bacteraemia is an important cause of illness and death in children. Our aim was to establish the magnitude and causes of hospital-acquired (nosocomial) bacteraemia in African children. METHODS: We reviewed prospectively collected surveillance data of 33,188 admissions to Kilifi District Hospital, Kenya, between April 16, 2002, and Sept 30, 2009. We defined bacteraemia as nosocomial if it occurred 48 h or more after admission. We estimated the per-admission risk, daily rate, effect on mortality, and microbial cause of nosocomial bacteraemia and analysed risk factors by multivariable Cox regression. The effect on morbidity was measured as the increase in hospital stay by comparison with time-matched patients without bacteraemia. FINDINGS: The overall risk of nosocomial bacteraemia during this period was 5·9/1000 admissions (95% CI 5·2-6·9) but we recorded an underlying rise in risk of 27% per year. The incidence was 1·0/1000 days in hospital (0·87-1·14), which is about 40 times higher than that of community-acquired bacteraemia in the same region. Mortality in patients with nosocomial bacteraemia was 53%, compared with 24% in community-acquired bacteraemia and 6% in patients without bacteraemia. In survivors, nosocomial bacteraemia lengthened hospital stay by 10·1 days (3·0-17·2). Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Acinetobacter spp, group D streptococci, and Pseudomonas aeruginosa accounted for three-quarters of nosocomial infections. Nosocomial bacteraemia was significantly associated with severe malnutrition (hazard ratio 2·52, 95% CI 1·79-3·57) and blood transfusion in children without severe anaemia (4·99; 3·39-7·37). INTERPRETATION: Our findings show that although nosocomial bacteraemia is rare, it has serious effects on morbidity and mortality, and the microbiological causes are distinct from those of community-acquired bacteraemia. Nosocomial infections are largely unrecognised or undocumented as a health risk in low-income countries, but they are likely to become public health priorities as awareness of their occurrence increases and as other prominent childhood diseases are progressively controlled. FUNDING: Wellcome Trust.

A Better Disinfectant for Low-Resourced Hospitals? A Multi-Period Cluster Randomised Trial Comparing Hypochlorous Acid with Sodium Hypochlorite in Nigerian Hospitals: The EWASH Trial.

Environmental hygiene in hospitals is a major challenge worldwide. Low-resourced hospitals in African countries continue to rely on sodium hypochlorite (NaOCl) as major disinfectant. However, NaOCl has several limitations such as the need for daily dilution, irritation, and corrosion. Hypochlorous acid (HOCl) is an innovative surface disinfectant produced by saline electrolysis with a much higher safety profile. We assessed non-inferiority of HOCl against standard NaOCl for surface disinfection in two hospitals in Abuja, Nigeria using a double-blind multi-period randomised cross-over study. Microbiological cleanliness [Aerobic Colony Counts (ACC)] was measured using dipslides. We aggregated data at the cluster-period level and fitted a linear regression. Microbiological cleanliness was high for both disinfectant (84.8% HOCl; 87.3% NaOCl). No evidence of a significant difference between the two products was found (RD = 2%, 90%CI: -5.1%-+0.4%; p-value = 0.163). We cannot rule out the possibility of HOCl being inferior by up to 5.1 percentage points and hence we did not strictly meet the non-inferiority margin we set ourselves. However, even a maximum difference of 5.1% in favour of sodium hypochlorite would not suggest there is a clinically relevant difference between the two products. We demonstrated that HOCl and NaOCl have a similar efficacy in achieving microbiological cleanliness, with HOCl acting at a lower concentration. With a better safety profile, and potential applicability across many healthcare uses, HOCl provides an attractive and potentially cost-efficient alternative to sodium hypochlorite in low resource settings.

Mortality associated with third-generation cephalosporin resistance in Enterobacteriaceae bloodstream infections at one South African hospital.

OBJECTIVES: Enterobacteriaceae are common pathogens causing bloodstream infection (BSI) in sub-Saharan Africa and frequently express third-generation cephalosporin (3GC) resistance; however, the impact of 3GC resistance on clinical outcomes is rarely studied. METHODS: We conducted a single-site prospective cohort study at Tygerberg Hospital, Cape Town, South Africa to examine the feasibility of measuring impacts of 3GC resistance in Enterobacteriaceae BSI. We included patients with 3GC-susceptible and 3GC-resistant BSIs and matched each BSI patient to two uninfected patients. We determined the concordance of initial antibiotic treatment with the corresponding isolate's susceptibility profile. We performed exploratory impact analysis using multivariable regression models. RESULTS: Between 1 June 2017 and 31 January 2018, we matched 177 Enterobacteriaceae BSI patients to 347 uninfected patients. Among these BSIs, 35% were phenotypically 3GC resistant. Parameters describing clinical comorbidity showed strong associations with mortality. We found that 18% of 3GC-R and 3% of 3GC-S BSI patient received non-concordant initial therapy. In multivariable Cox regression, we found a mortality impact over their matched patients for both 3GC-R (cause-specific hazard ratio 23.77; 95% CI 5.12-110.3) and 3GC-S (HR 7.49; 95%CI 3.08-18.19) BSI. There was a nonsignificant ratio of these ratios (HR 3.18; 95% CI 0.54-18.70), limited by the small sample size. CONCLUSION: This form of impact estimation was feasible in one hospital in South Africa where 3GC-R status was associated with non-concordant initial antibiotic treatment. There was a possible increase in mortality among individuals with 3GC-resistant Enterobacteriaceae, but with broad confidence intervals. These analytical approaches could be applied to larger datasets to improve precision of estimates.

Cleaning Neonatal Units in Low-resource Settings: A Hot-topic in Waiting?

Globally, about 3-quarters of births now occur in healthcare facilities, with the proportion being 50% for sub-Saharan Africa, where healthcare-associated infections among newborns are typically 3-20 times higher than in facilities in high-income countries. As this upward trend in institutional deliveries continues, the demand for specialized neonatal care also rises, with dedicated units often only available in tertiary referral hospitals in the case of low- and middle-income countries. Preventing nosocomial infections among vulnerable newborns requires effective and feasible control strategies and interventions. The role of cleaning and cleaners in reducing risks and maintaining a clean safe environment has until very recently been neglected at policy, program, practice, and research levels. There is now an opportunity to reposition cleaning within global and national initiatives related to Water, Sanitation and Hygiene, Infection Prevention and Control, and Antimicrobial Resistance. The evidence base should also be strengthened on cost-effective bundles of cleaning interventions, particularly in the context of low-resource settings. Here increasing overcrowding and shortages of staff and supplies present major threats to neonatal survival and well-being and heighten the case for optimizing the use of low-cost, back-to-basics interventions like cleaning.

The association between antimicrobial resistance and HIV infection: a systematic review and meta-analysis.

OBJECTIVES: People living with HIV (PLWH) are at increased risk of infections with resistant organisms due to more frequent healthcare utilization. Our objective was to investigate the association between HIV and antimicrobial resistance (AMR). METHODS: We searched MEDLINE, EMBASE, Web of Science, LILACS and African Journals Online. Studies were eligible if they reported on AMR for colonization or infection with bacterial pathogens (excluding mycobacteria and bacteria causing sexually transmitted infections) and were stratified by HIV status, species and antimicrobials tested. Pooled odds ratios were used to evaluate the association between HIV and resistance. RESULTS: In total, 92 studies published between 1995 and 2020 were identified. The studies included the following organisms: Staphylococcusaureus (n = 47), Streptococcus pneumoniae (n = 28), Escherichia coli (n = 6) and other Gram-negative bacteria. PLWH had a 2.12 (95%CI 1.36-3.30) higher odds for colonization and 1.90 (95%CI 1.45-2.48) higher odds for infection with methicillin-resistant S. aureus, a 2.28 (95%CI 1.75-2.97) higher odds of infection with S. pneumoniae with decreased penicillin susceptibility, and a 1.59 (95%CI 0.83-3.05) higher odds of resistance to third-generation cephalosporins in E. coli and Klebsiella pneumoniae. CONCLUSION: This review shows an increased risk of AMR in PLWH across a range of bacterial pathogens and multiple drug classes. The lack of laboratory capacity for identifying AMR, and limited access to alternative treatment options in countries with the highest burden of HIV, highlight the need for more research on AMR in PLWH. Overall, the quality of studies was moderate or low, which may impact the findings of this review.

Overuse of antibiotics in maternity and neonatal wards, a descriptive report from public hospitals in Dar es Salaam, Tanzania.

BACKGROUND: Overuse of antibiotics is a major challenge and undermines measures to control drug resistance worldwide. Postnatal women and newborns are at risk of infections and are often prescribed prophylactic antibiotics although there is no evidence to support their universal use in either group. METHODS: We performed point prevalence surveys in three hospitals in Dar es Salaam, Tanzania, in 2018 to collect descriptive data on antibiotic use and infections, in maternity and neonatal wards. RESULTS: Prescribing of antibiotics was high in all three hospitals ranging from 90% (43/48) to 100% (34/34) in women after cesarean section, from 1.4% (1/73) to 63% (30/48) in women after vaginal delivery, and from 89% (76/85) to 100% (77/77) in neonates. The most common reason for prescribing antibiotics was medical prophylaxis in both maternity and neonatal wards. CONCLUSIONS: We observed substantial overuse of antibiotics in postnatal women and newborns. This calls for urgent antibiotic stewardship programs in Tanzanian hospitals to curb this inappropriate use and limit the spread of antimicrobial resistance.

Postnatal infection surveillance by telephone in Dar es Salaam, Tanzania: An observational cohort study.

INTRODUCTION: Maternal and newborn infections are important causes of mortality but morbidity data from low- and middle-income countries is limited. We used telephone surveillance to estimate infection incidence and risk factors in women and newborns following hospital childbirth in Dar es Salaam. METHODS: We recruited postnatal women from two tertiary hospitals and conducted telephone interviews 7 and 28 days after delivery. Maternal infection (endometritis, caesarean or perineal wound, or urinary tract infection) and newborn infection (umbilical cord or possible severe bacterial infection) were identified using hospital case-notes at the time of birth and self-reported symptoms. Adjusted Cox regression models were used to assess the association between potential risk-factors and infection. RESULTS: We recruited 879 women and interviewed 791 (90%). From day 0-7, 6.7% (49/791) women and 6.2% (51/762) newborns developed infection. Using full follow-up data, the infection rate was higher in women with caesarean childbirth versus women with a vaginal delivery (aHR 1.93, 95%CI 1.11-3.36). Only 24% of women received pre-operative antibiotic prophylaxis before caesarean section. Infection was higher in newborns resuscitated at birth versus newborns who were not resuscitated (aHR 4.45, 95%CI 2.10-9.44). At interview, 66% (37/56) of women and 88% (72/82) of newborns with possible infection had sought health-facility care. CONCLUSIONS: Telephone surveillance identified a substantial risk of postnatal infection, including cases likely to have been missed by hospital-based data-collection alone. Risk of maternal endometritis and newborn possible severe bacterial infection were consistent with other studies. Caesarean section was the most important risk-factor for maternal infection. Improved implementation of pre-operative antibiotic prophylaxis is urgently required to mitigate this risk.

Association between SARS-CoV-2 exposure and antibody status among healthcare workers in two London hospitals: a cross-sectional study.

BACKGROUND: Patient-facing (frontline) health-care workers (HCWs) are at high risk of repeated exposure to SARS-CoV-2. AIM: We sought to determine the association between levels of frontline exposure and likelihood of SARS-CoV-2 seropositivity amongst HCW. METHODS: A cross-sectional study was undertaken using purposefully collected data from HCWs at two hospitals in London, United Kingdom (UK) over eight weeks in May-June 2020. Information on sociodemographic, clinical and occupational characteristics was collected using an anonymised questionnaire. Serology was performed using split SARS-CoV-2 IgM/IgG lateral flow immunoassays. Exposure risk was categorised into five pre-defined ordered grades. Multivariable logistic regression was used to examine the association between being frontline and SARS-CoV-2 seropositivity after controlling for other risks of infection. FINDINGS: 615 HCWs participated in the study. 250/615 (40.7%) were SARS-CoV-2 IgM and/or IgG positive. After controlling for other exposures, there was non-significant evidence of a modest association between being a frontline HCW (any level) and SARS-CoV-2 seropositivity compared to non-frontline status (OR 1.39, 95% CI 0.84-2.30, P=0.200). There was 15% increase in the odds of SARS-CoV-2 seropositivity for each step along the frontline exposure gradient (OR 1.15, 95% CI 1.00-1.32, P=0.043). CONCLUSION: We found a high SARS-CoV-2 IgM/IgG seropositivity with modest evidence for a dose-response association between increasing levels of frontline exposure risk and seropositivity. Even in well-resourced hospital settings, appropriate use of personal protective equipment, in addition to other transmission-based precautions for inpatient care of SARS-CoV-2 patients could reduce the risk of hospital-acquired SARS-CoV-2 infection among frontline HCW.

Erratum to: Mortality attributable to third-generation cephalosporin resistance in Gram-negative bloodstream infections in African hospitals: a multi-site retrospective study.

[This corrects the article DOI: 10.1093/jacamr/dlaa130.].

Mortality attributable to third-generation cephalosporin resistance in Gram-negative bloodstream infections in African hospitals: a multi-site retrospective study.

BACKGROUND: Bloodstream infections (BSI) caused by Enterobacteriaceae show increasing frequency of resistance to third-generation cephalosporin (3GC) antibiotics on the African continent but the mortality impact has not been quantified. METHODS: We used historic data from six African hospitals to assess the impact of 3GC resistance on clinical outcomes in Escherichia coli and Klebsiella pneumoniae BSI. We matched each bacteraemic patient to two uninfected patients. We compared outcomes between 3GC-susceptible and 3GC-resistant BSI and their respective uninfected controls using Cox regression models. RESULTS: For 1431 E. coli BSI patients, we matched 1152 (81%) 3GC-susceptible and 279 (19%) 3GC-resistant cases to 2263 and 546 uninfected inpatient controls. For 1368 K. pneumoniae BSI patients, we matched 502 (37%) 3GC-susceptible and 866 (63%) 3GC-resistant cases to 982 and 1656 uninfected inpatient controls. We found that 3GC-resistant E. coli had similar hazard ratios (HRs) for in-hospital mortality over their matched controls as compared to susceptible infections over their controls (ratio of HRs 1.03, 95% CI 0.73-1.46). Similarly, 3GC-resistance in K. pneumoniae BSI was not associated with mortality (ratio of HR 1.10, 95% CI 0.80-1.52). Estimates of mortality impact varied by site without a consistent pattern. CONCLUSIONS: In a retrospective analysis, including the use of matched uninfected patients, there did not appear to be an impact of 3GC-resistance on mortality in E. coli or K. pneumoniae BSI in African hospitals, as compared with susceptible BSI with equivalent species. Better information on the actual use of antibiotics in treating infections in African hospitals would improve these impact estimates.

The Clean pilot study: evaluation of an environmental hygiene intervention bundle in three Tanzanian hospitals.

BACKGROUND: Healthcare associated infections (HAI) are estimated to affect up to 15% of hospital inpatients in low-income countries (LICs). A critical but often neglected aspect of HAI prevention is basic environmental hygiene, particularly surface cleaning and linen management. TEACH CLEAN is an educational intervention aimed at improving environmental hygiene. We evaluated the effectiveness of this intervention in a pilot study in three high-volume maternity and newborn units in Dar es Salaam, Tanzania. METHODS: This study design prospectively evaluated the intervention as a whole, and offered a before-and-after comparison of the impact of the main training. We measured changes in microbiological cleanliness [Aerobic Colony Counts (ACC) and presence of Staphylococcus aureus] using dipslides, and physical cleaning action using gel dots. These were analysed with descriptive statistics and logistic regression models. We used qualitative (focus group discussions, in-depth interviews, and semi-structured observation) and quantitative (observation checklist) tools to measure why and how the intervention worked. We describe these findings across the themes of adaptation, fidelity, dose, reach and context. RESULTS: Microbiological cleanliness improved during the study period (ACC pre-training: 19%; post-training: 41%). The odds of cleanliness increased on average by 1.33 weekly during the pre-training period (CI = 1.11-1.60), and by 1.08 (CI = 1.03-1.13) during the post-training period. Cleaning action improved only in the pre-training period. Detection of S. aureus on hospital surfaces did not change substantially. The intervention was well received and considered feasible in this context. The major pitfalls in the implementation were the limited number of training sessions at the hospital level and the lack of supportive supervision. A systems barrier to implementation was lack of regular cleaning supplies. CONCLUSIONS: The evaluation suggests that improvements in microbiological cleanliness are possible using this intervention and can be sustained. Improved microbiological cleanliness is a key step on the pathway to infection prevention in hospitals. Future research should assess whether this bundle is cost-effective in reducing bacterial and viral transmission and infection using a rigorous study design.

The effect of behavioural interventions targeting hand hygiene practices among nurses in high-income hospital settings: a systematic review.

BACKGROUND: Hand hygiene is a critical behaviour for infection control but efforts to raise compliance among clinical professionals have been met with mixed success. The aim of this systematic review was to identify the effectiveness of the behaviour change techniques utilised in recent hand hygiene interventions that seek to improve hand hygiene compliance among nurses in hospitals in high-income countries. Nurses are at the frontline of healthcare delivery, and so improving their HH behaviour and thus increasing HHC rates will have a relatively large impact on reducing transmission and preventing healthcare acquired infections. METHODS: High-quality studies among nurses in high-income countries were surveyed from the scientific literature, following PRISMA guidelines, to identify which kinds of behaviour change mechanisms have been used to effectively increase hand hygiene compliance. Only seven studies met all inclusion criteria. A formal meta-analysis was not conducted due to the heterogeneity of the included studies. Instead, the review analysed studies in line with the Intervention Component Analysis approach to identify which differences in intervention characteristics appear to be important. Analysis proceeded in two steps: first, the Effective Practice and Organization of Care Data Extraction Checklist was used to identify the study design and to describe the intervention, target population, setting, results, outcome measures, and analytic approach. The second step involved inferring the behavioural change techniques used in the complex study interventions. Following coding, logic models were then inferred for each study to identify the Theory of Change behind each intervention. These Theories of Change were then examined for suggestions as to which BCTs were likely to have been responsible for any effectiveness observed. RESULTS: Goals and planning (to achieve specific ends), comparison of behaviour (to peers or some ideal) and feedback and monitoring (observing and providing feedback about behaviour or outcomes) were the most frequently used behaviour change technique groupings used across studies and within interventions. CONCLUSION: The complexity of the interventions used and lack of sufficient studies makes assignment of responsibility for behaviour change to specific behaviour change techniques difficult. Delivery channels and activities identified in the study Theories of Change were also highly individualized and so difficult to compare. However, we identified a temporal shift in types of techniques used in these recent studies on HH interventions, as compared with studies from prior to the review period. These newer interventions did not focus on providing access to alcohol-based hand rub or trying to solely encourage administrative support. Instead, they had nurses create goals and plan how to best facilitate HH, compared both individuals' and the group's behaviour to others, and focused on providing feedback.