Epidemiology of Citrobacter spp. infections among hospitalized patients: a systematic review and meta-analysis.

BACKGROUND: Infections due to Citrobacter species are increasingly observed in hospitalized patients and are often multidrug-resistant. Yet, the magnitude and burden of Citrobacter spp. resistance in the hospital setting have not been reported. We aimed to evaluate the epidemiology of Citrobacter spp. infections among hospitalized patients, their main resistance patterns and Citrobacter spp. involvement in hospital outbreaks. METHODS: We conducted a systematic review and meta-analysis of published literature (PROSPERO registration Jan-2023, CRD42023390084). We searched Embase, Medline and grey literature for studies on hospitalized patients diagnosed with Citrobacter spp. infections, and nosocomial outbreaks due to Citrobacter spp. published during the years 2000-2022. We included observational, interventional, surveillance studies and outbreak reports. Outcomes of interest were the frequency of Citrobacter spp. infections among hospitalized patients and 3rd generation cephalosporin and/or carbapenem resistance percentages in these infections. We used random-effects models to generate pooled outcome estimates and evaluated risk of bias and quality of reporting of outbreaks. RESULTS: We screened 1609 deduplicated publications, assessed 148 full-texts, and included 41 studies (15 observational, 13 surveillance and 13 outbreak studies). Citrobacter spp. urinary tract- and bloodstream infections were most frequently reported, with Citrobacter freundii being the main causative species. Hospital-acquired infection occurred in 85% (838/990) of hospitalized patients with Citrobacter infection. After 2010, an increasing number of patients with Citrobacter spp. infections was reported in observational studies. Pooled frequency estimates for Citrobacter spp. infections could not be generated due to lack of data. The pooled prevalence of ESBL and carbapenemase producers among Citrobacter isolates were 22% (95%CI 4-50%, 7 studies) and 18% (95%CI 0-63%, 4 studies), respectively. An increased frequency of reported Citrobacter outbreaks was observed after 2016, with an infection/colonization ratio of 1:3 and a case-fatality ratio of 7% (6/89 patients). Common outbreak sources were sinks, toilets, contaminated food and injection material. Implemented preventive measures included environmental cleaning, isolation of positive patients and reinforcement of hand hygiene. Only seven out of 13 outbreaks (54%) were definitively controlled. CONCLUSION: This review highlights the clinical importance of endemic and epidemic Citrobacter spp. in healthcare settings. As an emerging, multidrug­resistant nosocomial pathogen it requires heightened awareness and further dedicated surveillance efforts.

Risk factors for colonisation by Multidrug-Resistant bacteria in critical care units.

INTRODUCTION: Antimicrobial resistance is a major public health challenge recognised by the WHO as an urgent global healthcare concern. Patients in Intensive Care Units (ICUs) are particularly prone to colonisation and/or infection by multidrug-resistant organisms (MDROs). OBJECTIVES: Delineate the epidemiological characteristics and risk factors for MDROs colonisation in mixed ICUs and Resuscitation Units by focusing on initial and nosocomial colonisation. MATERIAL AND METHODS: A descriptive observational study with analytical elements. It uses the Zero-Resistance register from the Preventive Medicine Service of the Albacete General University Hospital (Spain) from April 2016 to December 2021. It identifies the risk factors for MDROs colonisation. RESULTS: Of 7,541 cases, 61.0 % with initial colonisation had risk factors for MDROs versus 34.0 % not colonised upon hospitalisation (p < 0.001). Significant risk factors for initial colonisation included hospitalisation for ≥ 5 days within the last 3 months, prior MDROs colonisation/infection and institutionalization. No significant risk factor differences were found for nosocomial colonisation. An association between longer ICU stays and nosocomial colonisation (p < 0.001) was noted. CONCLUSIONS: Significant risk factors for initial MDROs colonisation were hospitalisation for ≥ 5 days in the last 3 months, prior MDROs colonisation/infection and institutionalisation. Longer ICU stays increased the nosocomial colonisation risk. IMPLICATIONS FOR CLINICAL PRACTICE: This study underscores the importance to early identify and manage patients at risk for MDROs colonisation in ICUs. By recognising factors (i.e. previous hospitalisations, existing colonisation or infection, impact of prolonged ICU stay), healthcare providers can implement targeted strategies to mitigate the spread of MDROs; e.g. enhanced surveillance, stringent infection control measures and judicious antibiotics use. Our findings highlight the need for a comprehensive approach to manage antimicrobial resistance in critical care settings to ultimately improve patient outcomes and reduce MDROs burden in hospitals.

Measles in the vaccinated host.

A woman in her 40s known to have systemic lupus erythematosus presented with a maculopapular rash on her face, neck and chest following measles exposure. She had received a single-dose measles vaccine as a child in the 1970s and was therefore presumed to be immune, and thus not infectious. As a result, she was initially managed in an open bay. Measles virus IgM antibody in serum was undetectable; however, measles virus RNA was subsequently detected in throat swab by PCR, which is consistent with current infection. Measles is one of the most transmissible diseases in the world and cases are rising both in the UK and globally. Our case and literature review highlight the risk of vaccine failure in measles, especially in people who have not received two doses of the measles, mumps and rubella vaccine. It also highlights the challenges in diagnosing measles in previously vaccinated individuals.

Risk assessment and prediction of nosocomial infections based on surveillance data using machine learning methods.

BACKGROUND: Nosocomial infections with heavy disease burden are becoming a major threat to the health care system around the world. Through long-term, systematic, continuous data collection and analysis, Nosocomial infection surveillance (NIS) systems are constructed in each hospital; while these data are only used as real-time surveillance but fail to realize the prediction and early warning function. Study is to screen effective predictors from the routine NIS data, through integrating the multiple risk factors and Machine learning (ML) methods, and eventually realize the trend prediction and risk threshold of Incidence of Nosocomial infection (INI). METHODS: We selected two representative hospitals in southern and northern China, and collected NIS data from 2014 to 2021. Thirty-nine factors including hospital operation volume, nosocomial infection, antibacterial drug use and outdoor temperature data, etc. Five ML methods were used to fit the INI prediction model respectively, and to evaluate and compare their performance. RESULTS: Compared with other models, Random Forest showed the best performance (5-fold AUC = 0.983) in both hospitals, followed by Support Vector Machine. Among all the factors, 12 indicators were significantly different between high-risk and low-risk groups for INI (P < 0.05). After screening the effective predictors through importance analysis, prediction model of the time trend was successfully constructed (R2 = 0.473 and 0.780, BIC = -1.537 and -0.731). CONCLUSIONS: The number of surgeries, antibiotics use density, critical disease rate and unreasonable prescription rate and other key indicators could be fitted to be the threshold predictions of INI and quantitative early warning.

Limited impact of bacterial virulence on early mortality risk factors in Acinetobacter baumannii bacteremia observed in a Galleria mellonella model.

Acinetobacter baumannii (AB) has emerged as a major pathogen in vulnerable and severely ill patients. It remains unclear whether early mortality (EM) due to AB bacteremia is because of worse clinical characteristics of the infected patients or the virulence of the pathogen. In this study, we aimed to investigate the effect of AB virulence on EM due to bacteremia. This retrospective study included 138 patients with AB bacteremia (age: ≥ 18 years) who were admitted to a tertiary care teaching hospital in South Korea between 2015 and 2019. EM was defined as death occurring within 7 days of bacteremia onset. The AB clinical isolates obtained from the patients' blood cultures were injected into 15 Galleria mellonella larvae each, which were incubated for 5 days. Clinical isolates were classified into high- and low-virulence groups based on the number of dead larvae. Patients' clinical data were combined and subjected to multivariate Cox regression analyses to identify the risk factors for EM. In total, 48/138 (34.8%) patients died within 7 days of bacteremia onset. The Pitt bacteremia score was the only risk factor associated with EM. In conclusion, AB virulence had no independent effect on EM in patients with AB bacteremia.

Efficiency of polymyxin B treatment against nosocomial infection: a systematic review and meta-analysis.

Background: Some cohort studies have explored the effects and safety of polymyxin B (PMB) in comparison to other antibiotics for the treatment of nosocomial infections, yielding inconsistent results. This systematic review aims to explore the effectiveness and safety of PMB and compared it with other antibiotics. Methods: A systematic literature search was conducted in PubMed, Embase, the Cochrane Library, and Web of Science, searching specific terms to identify quantitative cohort studies or RCTs that compared the effects of PMB with other antibiotics in terms of their efficacy and safety. The Newcastle-Ottawa Scale (NOS) was conducted to evaluate the risk of bias of observational studies. Odds ratios with 95% confidence intervals were used for outcome assessment. We evaluated heterogeneity using the I 2 test. Results: A total of 22 observational trials were included in the analysis. The PMB group had a higher mortality rate compared to the control group (odds ratio: 1.84, 95% CI: 1.36-2.50, p<0.00001, I 2 = 73%). while, the ceftazidime-avibactam group demonstrated a distinct advantage with lower mortality rates, despite still exhibiting high heterogeneity (odds ratio 2.73, 95% confidence interval 1.59-4.69; p = 0.0003; I 2 = 53%). Additionally, the PMB group had a lower nephrotoxicity rate compared to the colistin group but exhibited high heterogeneity in the results (odds ratio 0.58, 95% CI 0.36-0.93; p = 0.02; I 2 = 73%). Conclusion: In patients with nosocomial infections, PMB is not superior to other antibiotics in terms of mortality, specifically when compared to ceftazidime-avibactam. However, PMB demonstrated an advantage in terms of nephrotoxicity compared to colistin.

Presentation, management, and outcomes of older compared to younger adults with hospital-acquired bloodstream infections in the intensive care unit: a multicenter cohort study.

PURPOSE: Older adults admitted to the intensive care unit (ICU) usually have fair baseline functional capacity, yet their age and frailty may compromise their management. We compared the characteristics and management of older (≥ 75 years) versus younger adults hospitalized in ICU with hospital-acquired bloodstream infection (HA-BSI). METHODS: Nested cohort study within the EUROBACT-2 database, a multinational prospective cohort study including adults (≥ 18 years) hospitalized in the ICU during 2019-2021. We compared older versus younger adults in terms of infection characteristics (clinical signs and symptoms, source, and microbiological data), management (imaging, source control, antimicrobial therapy), and outcomes (28-day mortality and hospital discharge). RESULTS: Among 2111 individuals hospitalized in 219 ICUs with HA-BSI, 563 (27%) were ≥ 75 years old. Compared to younger patients, these individuals had higher comorbidity score and lower functional capacity; presented more often with a pulmonary, urinary, or unknown HA-BSI source; and had lower heart rate, blood pressure and temperature at presentation. Pathogens and resistance rates were similar in both groups. Differences in management included mainly lower rates of effective source control achievement among aged individuals. Older adults also had significantly higher day-28 mortality (50% versus 34%, p < 0.001), and lower rates of discharge from hospital (12% versus 20%, p < 0.001) by this time. CONCLUSIONS: Older adults with HA-BSI hospitalized in ICU have different baseline characteristics and source of infection compared to younger patients. Management of older adults differs mainly by lower probability to achieve source control. This should be targeted to improve outcomes among older ICU patients.

Characterization and Antimicrobial Susceptibility Patterns of Enterococcus Species Isolated from Nosocomial Infections in a Saudi Tertiary Care Hospital over a Ten-Year Period (2012-2021).

INTRODUCTION: The Enterococcus genus is a common cause of nosocomial infections, with vancomycin-resistant enterococci (VRE) posing a significant treatment challenge. METHOD: This retrospective study, spanning ten years (2012 to 2021), analyzes antimicrobial susceptibility patterns of Enterococcus species from clinical samples in a Saudi Arabian tertiary care hospital. RESULT: A total of 1034 Enterococcus isolates were collected, 729 from general wards and 305 from intensive care unit (ICU) patients. VRE accounted for 15.9% of isolates. E. faecalis was the most common species (54.3% of isolates and 2.7% of VRE), followed by E. faecium (33.6% of isolates and 41.2% of VRE). E. faecium exhibited the highest resistance to ciprofloxacin (84.1%), ampicillin (81.6%), and rifampicin (80%), with daptomycin (0.6%) and linezolid (3.1%) showing the lowest resistance. In E. faecalis, ciprofloxacin resistance was highest (59.7%), followed by rifampicin (20.1%) and ampicillin (11.8%). Daptomycin (0%), linezolid (1.5%), and vancomycin (2.7%) had the lowest resistance. VRE cases had higher mortality rates compared to vancomycin-sensitive enterococci (VSE). CONCLUSION: Eight different strains of Enterocci were identified. E. faecalis was the most commonly identified strain, while E. faecium had the highest percentage of VRE. VRE cases had a significantly higher mortality rate than VSE cases.

Lysine grafted poly(lactic acid): An intrinsically antimicrobial polymer.

Nosocomial infections or healthcare-associated infections, normally develops after the healthcare treatment in the hospital. Most of them are caused by infected medical devices. Plastics are the most common materials for manufacturing these devices because of their good processability, sterilization efficacy, ease of handling and harmlessness, however, it usually do not display antimicrobial properties. Here, in order to infer antimicrobial activity to poly(lactic acid), it was modified by maleation, followed by l-lysine grafting to its structure. The chemical modifications were confirmed by FTIR and 1H NMR analysis, indicating the success of the reactions. The antimicrobial activity was tested using Escherichia coli and Staphylococcus aureus and the results showed that the sample was capable of inhibiting about 99 % of the S. aureus growth by contact. The samples cytotoxicity was also tested using the L929 mouse cells and the results indicated no cytotoxic effect. These results indicated the sample antimicrobial potential, without affect the normal eukaryotic cells. In addition, the processability of the modified PLA (PLA-g-Lys) was improved without compromising its mechanical properties, as shown by thermal analysis and tensile tests. Thus, this novel PLA derivative can be seen as a promising material for future applications in the manufacturing of biomedical devices.

Effects of coronavirus disease 2019 on the spread of respiratory-transmitted human-to-human bacteria.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has necessitated significant changes in medical systems, social behaviours, and non-pharmaceutical interventions (NPIs). We aimed to determine the effect of the COVID-19 pandemic on changes in the epidemiology of respiratory-transmitted bacteria that have been unexplored. METHODS: We utilised a comprehensive national surveillance database from 2018 to 2021 to compare monthly number of patients with four respiratory-transmitted human-to-human bacteria (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pyogenes) before and after the COVID-19 pandemic, stratified by specimen sources and age groups. RESULTS: The incidence of detected patients with S. pneumoniae, H. influenzae, and S. pyogenes from both respiratory and blood cultures significantly decreased from 2019 to 2020. In 2021, the incidence of detected patients with the respiratory-transmitted bacterial species, except for S. pyogenes, from respiratory cultures, increased again from April to July, primarily affecting the 0-4-year age group. CONCLUSIONS: Our comprehensive national surveillance data analysis demonstrates the dynamic changes and effects of NPIs on respiratory-transmitted bacteria during the COVID-19 pandemic, with variations observed among species, specimen sources, and age groups.

Architectural interventions to mitigate the spread of SARS-CoV-2 in emergency departments.

INTRODUCTION: Emergency departments (EDs) are a critical entry gate for infectious agents into hospitals. In this interdisciplinary study, we explore how infection prevention and control (IPC) architectural interventions mitigate the spread of emerging respiratory pathogens using the example of SARS-CoV-2 in a prototypical ED. METHODS: Using an agent-based approach, we integrated data on patients' and healthcare workers' (HCWs) routines and the architectural characteristics of key ED areas. We estimated the number of transmissions in the ED by modelling the interactions between and among patients and HCWs. Architectural interventions were guided towards the gradual separation of pathogen carriers, compliance with a minimum interpersonal distance, and deconcentrating airborne pathogens (higher air exchange rates (AERs)). Interventions were epidemiologically evaluated for their mitigation effects on diverse endpoints. RESULTS: Simulation results indicated that higher AERs in the ED (compared with baseline) may provide a moderate level of infection mitigation (incidence rate ratio (IRR) of 0.95 (95% confidence interval (CI) 0.93-0.98)) while the overall burden decreased more when rooms in examination areas were separated (IRR of 0.78 (95% CI 0.76-0.81)) or when the size of the ED base was increased (IRR of 0.79 (95% CI 0.78-0.81)). The reduction in SARS-CoV-2-associated nosocomial transmissions was largest when architectural interventions were combined (IRR of 0.61 (95% CI 0.59-0.63)). CONCLUSIONS: These modelling results highlight the importance of IPC architectural interventions; they can be devised independently of profound knowledge of an emerging pathogen, focusing on technical, constructive, and functional components. These results may inform public health decision-makers and hospital architects on how IPC architectural interventions can be optimally used in healthcare premises.

Quality improvement initiative 'S-A-F-H' to reduce healthcare-associated neonatal sepsis in a tertiary neonatal care unit.

BACKGROUND: Neonatal sepsis is a leading cause of morbidity and mortality among admitted neonates. Healthcare-associated infection (HAI) is a significant contributor in this cohort. LOCAL PROBLEM: In our unit, 16.1% of the admissions developed sepsis during their stay in the unit. METHOD: We formed a team of all stakeholders to address the issue. The problem was analysed using various tools, and the main contributing factor was low compliance with hand hygiene and handling of intravenous lines. INTERVENTIONS: The scrub the hub/aseptic non-touch technique/five moments of hand hygiene/hand hygiene (S-A-F-H) protocol was formulated as a quality improvement initiative, and various interventions were done to ensure compliance with hand hygiene, five moments of hand hygiene, aseptic non-touch technique. The data were collected and analysed regularly with the team members, and actions were planned accordingly. RESULTS: Over a few months, the team could reduce the incidence of HAI by 50%, which has been sustained for over a year. The improvement in compliance with the various aspects of S-A-F-H increased. CONCLUSIONS: Compliance with hand hygiene steps, five moments of hand hygiene and an aseptic non-touch technique using quality improvement methodology led to a reduction in neonatal sepsis incidence in the unit. Regular reinforcement is required to maintain awareness of asepsis practices and implementation in day-to-day care and to bring about behavioural changes.

Linezolid and vancomycin for nosocomial infections in pediatric patients: a systematic review

Abstract Objective: To investigate the effectiveness of linezolid and vancomycin for the treatment of nosocomial infections in children under 12 years old. Data sources: This is a systematic review in which five randomized clinical trials about the effectiveness of linezolid and vancomycin, involving a total of 429 children with nosocomial infections, were evaluated. They were searched in scientific databases: PubMed, Bvs, and SciELO. Summary of findings: The main nosocomial infections that affected children were bacteremia, skin, and soft tissue infections followed by nosocomial pneumonia. Most infections were caused by Gram-positive bacteria, which all studies showed infections caused by Staphylococcus aureus, with methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci strains being isolated. Both linezolid and vancomycin showed high therapeutic efficacy against different types of nosocomial infections, ranging from 84.4% to 94% for linezolid and 76.9% to 90% for vancomycin. Patients receiving linezolid had lower rates of rash and red man syndrome compared to those receiving vancomycin. However, despite the adverse reactions, antimicrobials can be safely administered to children to treat nosocomial infections caused by resistant Gram-positive bacteria. Conclusion: Both linezolid and vancomycin showed good efficacy in the treatment of bacterial infections caused by resistant Gram-positive bacteria in hospitalized children. However, linezolid stands out regarding its pharmacological safety. Importantly, to strengthen this conclusion, further clinical trials are needed to provide additional evidence.

Pathogenesis and therapeutic opportunities of gut microbiome dysbiosis in critical illness.

For many years, it has been hypothesized that pathological changes to the gut microbiome in critical illness is a driver of infections, organ dysfunction, and other adverse outcomes in the intensive care unit (ICU). The advent of contemporary microbiome methodologies and multi-omics tools have allowed researchers to test this hypothesis by dissecting host-microbe interactions in the gut to better define its contribution to critical illness pathogenesis. Observational studies of patients in ICUs have revealed that gut microbial communities are profoundly altered in critical illness, characterized by markedly reduced alpha diversity, loss of commensal taxa, and expansion of potential pathogens. These key features of ICU gut dysbiosis have been associated with adverse outcomes including life-threatening hospital-acquired (nosocomial) infections. Current research strives to define cellular and molecular mechanisms connecting gut dysbiosis with infections and other outcomes, and to identify opportunities for therapeutic modulation of host-microbe interactions. This review synthesizes evidence from studies of critically ill patients that have informed our understanding of intestinal dysbiosis in the ICU, mechanisms linking dysbiosis to infections and other adverse outcomes, as well as clinical trials of microbiota-modifying therapies. Additionally, we discuss novel avenues for precision microbial therapeutics to combat nosocomial infections and other life-threatening complications of critical illness.

Gram-negative bacteremia, the risk factors, and outcome in children.

We aimed to determine the epidemiology and resistance patterns of Gram-negative bacteria, the risk factors and outcome of bloodstream infection (BSI). In all, 412 episodes in children who were hospitalized with the diagnosis of bacteremia were analyzed. The most common microorganisms were Klebsiella spp. (43.9%), Escherichia coli (13.5 %) and Acinetobacter spp. (10.6 %). Among isolates, 41.2 % were multidrug-resistant, 13.5 % were extensively drug-resistant and 0.4 % were pan-drug-resistant. Carbapenem resistance was revealed in 27.6 % of isolates. Carbapenem and colistin resistance increased over the years. The most common risk factors were the presence of a central-venous catheter and pediatric intensive care unit admission. Clinical response and infection-related mortality were significantly different in cases infected with carbapenem-resistant gram-negative (CRGN) vs carbapenem-susceptible gram-negative bacteria. The increase in multi-resistant Klebsiella spp. seems to be the biggest obstacles in fight against nosocomial infections. The increasing number of CRGN infections over the years affects both the clinical response and mortality rate of BSI.

Varicella zoster virus outbreak in a long-term care unit of a tertiary care hospital in northern India.

Nosocomial outbreak of varicella zoster virus (VZV) has been reported when susceptible individuals encounter a case of chicken pox or shingles. A suspected VZV outbreak was investigated in a 50-bedded in-patient facility of Physical Medicine and Rehabilitation in a tertiary care multispecialty hospital. A 30-year-old female patient admitted with Pott's spine was clinically diagnosed with chicken pox on 31 December 2022. The following week, four more cases were identified in the same ward. All cases were diagnosed as laboratory-confirmed varicella zoster infection by PCR. Primary case was a housekeeping staff who was clinically diagnosed with chicken pox 3 weeks prior (9 December 2022). He returned to work on eighth day of infection (17 December 2022) after apparent clinical recovery but before the lesions had crusted over. Thirty-one HCWs were identified as contacts a and three had no evidence of immunity. Two of these susceptible HCWs had onset of chickenpox shortly after first dose of VZV vaccination was inoculated. All cases recovered after treatment with no reported complications. VZV infection is highly contagious in healthcare settings with susceptible populations. Prompt identification of cases and implementation of infection prevention and control measures like patient isolation and vaccination are essential for the containment of outbreaks.

Ventilator-Associated Pneumonia, Ventilator-Associated Events, and Nosocomial Respiratory Viral Infections on the Leeside of the Pandemic.

The COVID-19 pandemic has had an unprecedented impact on population health and hospital operations. Over 7 million patients have been hospitalized for COVID-19 thus far in the United States alone. Mortality rates for hospitalized patients during the first wave of the pandemic were > 30%, but as we enter the fifth year of the pandemic hospitalizations have fallen and mortality rates for hospitalized patients with COVID-19 have plummeted to 5% or less. These gains reflect lessons learned about how to optimize respiratory support for different kinds of patients, targeted use of therapeutics for patients with different manifestations of COVID-19 including immunosuppressants and antivirals as appropriate, and high levels of population immunity acquired through vaccines and natural infections. At the same time, the pandemic has helped highlight some longstanding sources of harm for hospitalized patients including hospital-acquired pneumonia, ventilator-associated events (VAEs), and hospital-acquired respiratory viral infections. We are, thankfully, on the leeside of the pandemic at present; but the large increases in ventilator-associated pneumonia (VAP), VAEs, bacterial superinfections, and nosocomial respiratory viral infections associated with the pandemic beg the question of how best to prevent these complications moving forward. This paper reviews the burden of hospitalization for COVID-19, the intersection between COVID-19 and both VAP and VAEs, the frequency and impact of hospital-acquired respiratory viral infections, new recommendations on how best to prevent VAP and VAEs, and current insights into effective strategies to prevent nosocomial spread of respiratory viruses.

Longitudinal analysis within one hospital in sub-Saharan Africa over 20 years reveals repeated replacements of dominant clones of Klebsiella pneumoniae and stresses the importance to include temporal patterns for vaccine design considerations.

BACKGROUND: Infections caused by multidrug-resistant gram-negative bacteria present a severe threat to global public health. The WHO defines drug-resistant Klebsiella pneumoniae as a priority pathogen for which alternative treatments are needed given the limited treatment options and the rapid acquisition of novel resistance mechanisms by this species. Longitudinal descriptions of genomic epidemiology of Klebsiella pneumoniae can inform management strategies but data from sub-Saharan Africa are lacking. METHODS: We present a longitudinal analysis of all invasive K. pneumoniae isolates from a single hospital in Blantyre, Malawi, southern Africa, from 1998 to 2020, combining clinical data with genome sequence analysis of the isolates. RESULTS: We show that after a dramatic increase in the number of infections from 2016 K. pneumoniae becomes hyperendemic, driven by an increase in neonatal infections. Genomic data show repeated waves of clonal expansion of different, often ward-restricted, lineages, suggestive of hospital-associated transmission. We describe temporal trends in resistance and surface antigens, of relevance for vaccine development. CONCLUSIONS: Our data highlight a clear need for new interventions to prevent rather than treat K. pneumoniae infections in our setting. Whilst one option may be a vaccine, the majority of cases could be avoided by an increased focus on and investment in infection prevention and control measures, which would reduce all healthcare-associated infections and not just one.

Evaluation of hospital-onset bacteraemia and fungaemia in the USA as a potential healthcare quality measure: a cross-sectional study.

BACKGROUND: Hospital-onset bacteraemia and fungaemia (HOB) is being explored as a surveillance and quality metric. The objectives of the current study were to determine sources and preventability of HOB in hospitalised patients in the USA and to identify factors associated with perceived preventability. METHODS: We conducted a cross-sectional study of HOB events at 10 academic and three community hospitals using structured chart review. HOB was defined as a blood culture on or after hospital day 4 with growth of one or more bacterial or fungal organisms. HOB events were stratified by commensal and non-commensal organisms. Medical resident physicians, infectious disease fellows or infection preventionists reviewed charts to determine HOB source, and infectious disease physicians with training in infection prevention/hospital epidemiology rated preventability from 1 to 6 (1=definitely preventable to 6=definitely not preventable) using a structured guide. Ratings of 1-3 were collectively considered 'potentially preventable' and 4-6 'potentially not preventable'. RESULTS: Among 1789 HOB events with non-commensal organisms, gastrointestinal (including neutropenic translocation) (35%) and endovascular (32%) were the most common sources. Overall, 636/1789 (36%) non-commensal and 238/320 (74%) commensal HOB events were rated potentially preventable. In logistic regression analysis among non-commensal HOB events, events attributed to intravascular catheter-related infection, indwelling urinary catheter-related infection and surgical site infection had higher odds of being rated preventable while events with neutropenia, immunosuppression, gastrointestinal sources, polymicrobial cultures and previous positive blood culture in the same admission had lower odds of being rated preventable, compared with events without those attributes. Of 636 potentially preventable non-commensal HOB events, 47% were endovascular in origin, followed by gastrointestinal, respiratory and urinary sources; approximately 40% of those events would not be captured through existing healthcare-associated infection surveillance. DISCUSSION: Factors identified as associated with higher or lower preventability should be used to guide inclusion, exclusion and risk adjustment for an HOB-related quality metric.