Evaluation of an infection control link nurse program: an analysis using the RE-AIM framework.

BACKGROUND: Important elements of programs that train and support infection control link nurses (ICLN) are the engagement of stakeholders, support from hospital and ward management and a structure for iterative improvement. The effects of programs, that combine all these elements, are unknown. We evaluated such a comprehensive program to explore its impact on link nurses and infection prevention practices and routines. METHODS: We used the RE-AIM framework, a robust, evidence-based framework within the field of Implementation Science, to evaluate the impact of our ICLN training and support program. We used a mixed methods approach and organized the outcomes along its five dimensions: Reach, Effectiveness, Adoption, Implementation and Maintenance. RESULTS: Between 2014 and 2018, on average 91% of the inpatient wards and 58% of the outpatient clinics participated in the program (Reach) and impacted guideline adherence in inpatient wards. Link nurses felt engaged and empowered, and perceived their contribution to these results as pivotal. Ward managers confirmed the value of ICLN to help with implementing IPC practices (Effectiveness). The program was adopted both at the hospital and at the ward level (Adoption). Based on ongoing evaluations, the program was adapted by refining education, training and support strategies with emphasis on ward specific aspects (Implementation). The ICLN program was described as a key component of the infection prevention policy to sustain its effects (Maintenance). CONCLUSIONS: Our infection control link nurse program helped ICLN to improve infection prevention practices, especially in inpatient wards. The key to these improvements lay within the adaptability of our link nurse program. The adjustments to the program led to a shift of focus from hospital goals to goals tailored to the ward level. It allowed us to tailor activities to align them with the needs specific to each ward.

Esophageal microbiota composition and outcome of esophageal cancer treatment: a systematic review.

BACKGROUND: The role of esophageal microbiota in esophageal cancer treatment is gaining renewed interest, largely driven by novel DNA-based microbiota analysis techniques. The aim of this systematic review is to provide an overview of current literature on the possible association between esophageal microbiota and outcome of esophageal cancer treatment, including tumor response to (neo)adjuvant chemo(radio)therapy, short-term surgery-related complications, and long-term oncological outcome. METHODS: A systematic review of literature was performed, bibliographic databases were searched and relevant articles were selected by two independent researchers. The Newcastle-Ottawa scale was used to estimate the quality of included studies. RESULTS: The search yielded 1303 articles, after selection and cross-referencing, five articles were included for qualitative synthesis and four studies were considered of good quality. Two articles addressed tumor response to neoadjuvant chemotherapy and described a correlation between high intratumoral Fusobacterium nucleatum levels and a poor response. One study assessed surgery-related complications, in which no direct association between esophageal microbiota and occurrence of complications was observed. Three studies described a correlation between shortened survival and high levels of intratumoral F. nucleatum, a low abundance of Proteobacteria and high abundances of Prevotella and Streptococcus species. CONCLUSIONS: Current evidence points towards an association between esophageal microbiota and outcome of esophageal cancer treatment and justifies further research. Whether screening of the individual esophageal microbiota can be used to identify and select patients with a predisposition for adverse outcome needs to be further investigated. This could lead to the development of microbiota-based interventions to optimize esophageal microbiota composition, thereby improving outcome of patients with esophageal cancer.

Gastric acid suppression, lifestyle factors and intestinal carriage of ESBL and carbapenemase-producing Enterobacterales: a nationwide population-based study.

BACKGROUND: Gastric acid-suppressive therapy has been suggested to increase the risk for intestinal carriage of MDR Enterobacterales, but there is scarce community-based evidence substantiating this risk. OBJECTIVES: To investigate if acid-suppressant use is associated with a risk of intestinal carriage of ESBL and carbapenemase-producing Enterobacterales (ESBL-E) in the open population, and to assess possible modifying factors. METHODS: Within the framework of a nationwide seroprevalence study, we identified a population-based cross-sectional cohort comprising 2746 adults (≥18 years), who provided stool specimens between February 2016 and June 2017. Specimens were tested by phenotypic assays and confirmatory genotype analysis to detect carriage of ESBL-E. Covariate data were extracted from self-administered questionnaires. ORs and 95% CIs were estimated using multivariable multilevel logistic regression, controlling for confounders informed by directed acyclic graphs. RESULTS: Among 2746 participants, 316 (11.5%) used acid suppressants; the prevalence of ESBL-E carriage was 7.4% (95% CI, 6.1%-8.6%). Current use of acid suppressants was not associated with ESBL-E carriage (adjusted OR [aOR], 1.05; 95% CI, 0.64-1.74); lifestyle and comorbidity did not modify this association. A higher BMI (≥25 kg/m2) (aOR, 1.42 [95% CI, 1.02-1.98]), non-Western ethnic origin (aOR, 1.96 [95% CI, 1.34-2.87]), travel to Eastern-Mediterranean, Western-Pacific or South-East Asia regions (aOR, 3.16 [95% CI, 1.71-5.83]) were associated with ESBL-E carriage. Sensitivity analyses confirmed these results; spline analysis supported a BMI-associated risk. CONCLUSIONS: In this open population study, current use of acid suppressants was not associated with ESBL-E carriage. Travel to high-endemic regions and non-Western ethnicity were confirmed as risk factors, while a higher BMI emerged as a potential new risk for ESBL-E carriage.

A Test-Negative Design with Additional Population Controls Can Be Used to Rapidly Study Causes of the SARS-CoV-2 Epidemic.

Testing of symptomatic persons for infection with severe acute respiratory syndrome coronavirus-2 is occurring worldwide. We propose two types of case-control studies that can be carried out jointly in test settings for symptomatic persons. The first, the test-negative case-control design (TND) is the easiest to implement; it only requires collecting information about potential risk factors for Coronavirus Disease 2019 (COVID-19) from the tested symptomatic persons. The second, standard case-control studies with population controls, requires the collection of data on one or more population controls for each person who is tested in the test facilities, so that test-positives and test-negatives can each be compared with population controls. The TND will detect differences in risk factors between symptomatic persons who have COVID-19 (test-positives) and those who have other respiratory infections (test-negatives). However, risk factors with effect sizes of equal magnitude for both COVID-19 and other respiratory infections will not be identified by the TND. Therefore, we discuss how to add population controls to compare with the test-positives and the test-negatives, yielding two additional case-control studies. We describe two options for population control groups: one composed of accompanying persons to the test facilities, the other drawn from existing country-wide healthcare databases. We also describe other possibilities for population controls. Combining the TND with population controls yields a triangulation approach that distinguishes between exposures that are risk factors for both COVID-19 and other respiratory infections, and exposures that are risk factors for just COVID-19. This combined design can be applied to future epidemics, but also to study causes of nonepidemic disease.

Genomic Characterization of Colistin Heteroresistance in Klebsiella pneumoniae during a Nosocomial Outbreak.

Klebsiella pneumoniae is emerging as an important nosocomial pathogen due to its rapidly increasing multidrug resistance, which has led to a renewed interest in polymyxin antibiotics, such as colistin, as antibiotics of last resort. However, heteroresistance (i.e., the presence of a subpopulation of resistant bacteria in an otherwise susceptible culture) may hamper the effectiveness of colistin treatment in patients. In a previous study, we showed that colistin resistance among extended-spectrum-beta-lactamase (ESBL)-producing K. pneumoniae isolates emerged after the introduction of selective digestive tract decontamination (SDD) in an intensive care unit (ICU). In this study, we investigated heteroresistance to colistin among ESBL-producing K. pneumoniae isolates by using population analysis profiles (PAPs). We used whole-genome sequencing (WGS) to identify the mutations that were associated with the emergence of colistin resistance in these K. pneumoniae isolates. We found five heteroresistant subpopulations, with colistin MICs ranging from 8 to 64 mg/liter, which were derived from five clonally related, colistin-susceptible clinical isolates. WGS revealed the presence of mutations in the lpxM, mgrB, phoQ, and yciM genes in colistin-resistant K. pneumoniae isolates. In two strains, mgrB was inactivated by an IS3-like or ISKpn14 insertion sequence element. Complementation in trans with the wild-type mgrB gene resulted in these strains reverting to colistin susceptibility. The MICs for colistin-susceptible strains increased 2- to 4-fold in the presence of the mutated phoQ, lpxM, and yciM alleles. In conclusion, the present study indicates that heteroresistant K. pneumoniae subpopulations may be selected for upon exposure to colistin. Mutations in mgrB and phoQ have previously been associated with colistin resistance, but we provide experimental evidence for roles of mutations in the yciM and lpxM genes in the emergence of colistin resistance in K. pneumoniae.

Long-term Mortality After Rapid Screening and Decolonization of Staphylococcus Aureus Carriers: Observational Follow-up Study of a Randomized, Placebo-controlled Trial.

OBJECTIVE: To identify patients who benefit most from Staphylococcus aureus screening and decolonization treatment upon admission. BACKGROUND: S. aureus carriers are at increased risk of developing surgical-site infections with S. aureus. Previously, we demonstrated in a randomized, placebo-controlled trial (RCT) that these infections can largely be prevented by detection of carriage and decolonization treatment upon admission. In this study, we analyzed 1- and 3-year mortality rates in both treatment arms of the RCT to identify patient groups that should be targeted when implementing the screen-and-treat strategy. METHODS: Three years after enrolment in the RCT, mortality dates of all surgical patients were checked. One- and 3-year mortality rates were calculated for all patients and for various subgroups. RESULTS: After 3 years, 44 of 431 (10.2%) and 43 of 362 (11.9%) patients had died in the mupirocin/chlorhexidine and placebo groups, respectively. No significant differences in mortality rates were observed between the treatment groups or the subgroups according to type of surgery. In the subgroup of patients with clean procedures (382 cardiothoracic, 167 orthopedic, 61 vascular, and 56 other), mupirocin/chlorhexidine reduced 1-year mortality: 11 of 365 (3.0%) died in the mupirocin/chlorhexidine versus 21 of 301 (7.0%) in the placebo group [hazard ratio = 0.38 (95% CI: 0.18-0.81)]. CONCLUSIONS: Detection and decolonization of S. aureus carriage not only prevents S. aureus surgical-site infections but also reduces 1-year mortality in surgical patients undergoing clean procedures. Such patients with a high risk of developing S. aureus infections should therefore be the primary target when implementing the screen-and-treat strategy in clinical practice.

Infection of zebrafish embryos with live fluorescent Streptococcus pneumoniae as a real-time pneumococcal meningitis model.

BACKGROUND: Streptococcus pneumoniae is one of the most important causes of bacterial meningitis, an infection where unfavourable outcome is driven by bacterial and host-derived toxins. In this study, we developed and characterized a pneumococcal meningitis model in zebrafish embryos that allows for real-time investigation of early host-microbe interaction. METHODS: Zebrafish embryos were infected in the caudal vein or hindbrain ventricle with green fluorescent wild-type S. pneumoniae D39 or a pneumolysin-deficient mutant. The kdrl:mCherry transgenic zebrafish line was used to visualize the blood vessels, whereas phagocytic cells were visualized by staining with far red anti-L-plastin or in mpx:GFP/mpeg1:mCherry zebrafish, that have green fluorescent neutrophils and red fluorescent macrophages. Imaging was performed by fluorescence confocal and time-lapse microscopy. RESULTS: After infection by caudal vein, we saw focal clogging of the pneumococci in the blood vessels and migration of bacteria through the blood-brain barrier into the subarachnoid space and brain tissue. Infection with pneumolysin-deficient S. pneumoniae in the hindbrain ventricle showed attenuated growth and migration through the brain as compared to the wild-type strain. Time-lapse and confocal imaging revealed that the initial innate immune response to S. pneumoniae in the subarachnoid space mainly consisted of neutrophils and that pneumolysin-mediated cytolytic activity caused a marked reduction of phagocytes. CONCLUSIONS: This new meningitis model permits detailed analysis and visualization of host-microbe interaction in pneumococcal meningitis in real time and is a very promising tool to further our insights in the pathogenesis of pneumococcal meningitis.

Automated Broad-Range Molecular Detection of Bacteria in Clinical Samples.

Molecular detection methods, such as quantitative PCR (qPCR), have found their way into clinical microbiology laboratories for the detection of an array of pathogens. Most routinely used methods, however, are directed at specific species. Thus, anything that is not explicitly searched for will be missed. This greatly limits the flexibility and universal application of these techniques. We investigated the application of a rapid universal bacterial molecular identification method, IS-pro, to routine patient samples received in a clinical microbiology laboratory. IS-pro is a eubacterial technique based on the detection and categorization of 16S-23S rRNA gene interspace regions with lengths that are specific for each microbial species. As this is an open technique, clinicians do not need to decide in advance what to look for. We compared routine culture to IS-pro using 66 samples sent in for routine bacterial diagnostic testing. The samples were obtained from patients with infections in normally sterile sites (without a resident microbiota). The results were identical in 20 (30%) samples, IS-pro detected more bacterial species than culture in 31 (47%) samples, and five of the 10 culture-negative samples were positive with IS-pro. The case histories of the five patients from whom these culture-negative/IS-pro-positive samples were obtained suggest that the IS-pro findings are highly clinically relevant. Our findings indicate that an open molecular approach, such as IS-pro, may have a high added value for clinical practice.

Whole-Genome Multilocus Sequence Typing of Extended-Spectrum-Beta-Lactamase-Producing Enterobacteriaceae.

Molecular typing has become indispensable in the detection of nosocomial transmission of bacterial pathogens and the identification of sources and routes of transmission in outbreak settings, but current methods are labor-intensive, are difficult to standardize, or have limited resolution. Whole-genome multilocus sequence typing (wgMLST) has emerged as a whole-genome sequencing (WGS)-based gene-by-gene typing method that may overcome these limitations and has been applied successfully for several species in outbreak settings. In this study, genus-, genetic-complex-, and species-specific wgMLST schemes were developed for Citrobacter spp., the Enterobacter cloacae complex, Escherichia coli, Klebsiella oxytoca, and Klebsiella pneumoniae and used to type a national collection of 1,798 extended-spectrum-beta-lactamase-producing Enterobacteriaceae (ESBL-E) isolates obtained from patients in Dutch hospitals. Genus-, genetic-complex-, and species-specific thresholds for genetic distance that accurately distinguish between epidemiologically related and unrelated isolates were defined for Citrobacter spp., the E. cloacae complex, E. coli, and K. pneumoniae wgMLST was shown to have higher discriminatory power and typeability than in silico MLST. In conclusion, the wgMLST schemes developed in this study facilitate high-resolution WGS-based typing of the most prevalent ESBL-producing species in clinical practice and may contribute to further elucidation of the complex epidemiology of antimicrobial-resistant Enterobacteriaceae wgMLST opens up possibilities for the creation of a Web-accessible database for the global surveillance of ESBL-producing bacterial clones.

Assessment of appropriate antimicrobial prescribing: do experts agree?

OBJECTIVES: Little is known about the validity and reliability of expert assessments of the quality of antimicrobial prescribing, despite their importance in antimicrobial stewardship. We investigated how infectious disease doctors' assessments compared with a reference standard (modal expert opinion) and with the assessments of their colleagues. METHODS: Twenty-four doctors specialized in infectious diseases or clinical microbiology (16 specialists and 8 residents) from five hospitals were asked to assess the appropriateness of antimicrobial agents prescribed for a broad spectrum of indications in 56 paper cases. They were instructed how to handle guideline applicability and deviations. We created a reference standard of antimicrobial appropriateness using the modal assessment of 16 specialists. We calculated criterion validity and interrater and intrarater overall and specific agreement with an index expert (senior infectious disease physician) and analysed the influence of doctor characteristics on validity. RESULTS: Specialists agreed with the reference standard in 80% of cases (range 75%-86%), with a sensitivity and specificity of 75% and 84%, respectively. This did not differ by clinical specialty, hospital or years of experience, and residents had similar results. Specialists agreed with the index expert in 76% of cases and the index expert agreed with his previous assessments in 71% of cases. CONCLUSIONS: Doctors specialized in infectious diseases and clinical microbiology assess the appropriateness of antimicrobials prescribed for a broad spectrum of indications with acceptable agreement and validity, regardless of their experience or hospital of employment. However, there is room for improvement, which merits attention in multidisciplinary discussions and education.

Rapid, accurate, and on-site detection of C. difficile in stool samples.

OBJECTIVES: A rapid test to diagnose Clostridium difficile infection (CDI) on hospital wards could minimize common but critical diagnostic delay. Field asymmetric ion mobility spectrometry (FAIMS) is a portable mass spectrometry instrument that quickly analyses the chemical composition of gaseous mixtures (e.g., above a stool sample). Can FAIMS accurately distinguish C. difficile-positive from -negative stool samples? METHODS: We analyzed 213 stool samples with FAIMS, of which 71 were C. difficile positive by microbiological analysis. The samples were divided into training, test, and validation samples. We used the training and test samples (n=135) to identify which sample characteristics discriminate between positive and negative samples, and to build machine learning algorithms interpreting these characteristics. The best performing algorithm was then prospectively validated on new, blinded validation samples (n=78). The predicted probability of CDI (as calculated by the algorithm) was compared with the microbiological test results (direct toxin test and culture). RESULTS: Using a Random Forest classification algorithm, FAIMS had a high discriminatory ability on the training and test samples (C-statistic 0.91 (95% confidence interval (CI): 0.86-0.97)). When applied to the blinded validation samples, the C-statistic was 0.86 (0.75-0.97). For samples analyzed ≤7 days of collection (n=76), diagnostic accuracy was even higher (C-statistic: 0.93 (0.85-1.00)). A cutoff value of 0.32 for predicted probability corresponded with a sensitivity of 92.3% (95% CI: 77.4-98.6%) and specificity of 86.0% (78.3-89.3%). For even fresher samples, discriminatory ability further increased. CONCLUSIONS: FAIMS analysis of unprocessed stool samples can differentiate between C. difficile-positive and -negative samples with high diagnostic accuracy.

Role of the Environment in the Transmission of Antimicrobial Resistance to Humans: A Review.

To establish a possible role for the natural environment in the transmission of clinically relevant AMR bacteria to humans, a literature review was conducted to systematically collect and categorize evidence for human exposure to extended-spectrum ß-lactamase-producing Enterobacteriaceae, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus spp. in the environment. In total, 239 datasets adhered to inclusion criteria. AMR bacteria were detected at exposure-relevant sites (35/38), including recreational areas, drinking water, ambient air, and shellfish, and in fresh produce (8/16). More datasets were available for environmental compartments (139/157), including wildlife, water, soil, and air/dust. Quantitative data from exposure-relevant sites (6/35) and environmental compartments (11/139) were scarce. AMR bacteria were detected in the contamination sources (66/66) wastewater and manure, and molecular data supporting their transmission from wastewater to the environment (1/66) were found. The abundance of AMR bacteria at exposure-relevant sites suggests risk for human exposure. Of publications pertaining to both environmental and human isolates, however, only one compared isolates from samples that had a clear spatial and temporal relationship, and no direct evidence was found for transmission to humans through the environment. To what extent the environment, compared to the clinical and veterinary domains, contributes to human exposure needs to be quantified. AMR bacteria in the environment, including sites relevant for human exposure, originate from contamination sources. Intervention strategies targeted at these sources could therefore limit emission of AMR bacteria to the environment.

General secretion signal for the mycobacterial type VII secretion pathway.

Mycobacterial pathogens use specialized type VII secretion (T7S) systems to transport crucial virulence factors across their unusual cell envelope into infected host cells. These virulence factors lack classical secretion signals and the mechanism of substrate recognition is not well understood. Here we demonstrate that the model T7S substrates PE25/PPE41, which form a heterodimer, are targeted to the T7S pathway ESX-5 by a signal located in the C terminus of PE25. Site-directed mutagenesis of residues within this C terminus resulted in the identification of a highly conserved motif, i.e., YxxxD/E, which is required for secretion. This motif was also essential for the secretion of LipY, another ESX-5 substrate. Pathogenic mycobacteria have several different T7S systems and we identified a PE protein that is secreted by the ESX-1 system, which allowed us to compare substrate recognition of these two T7S systems. Surprisingly, this ESX-1 substrate contained a C-terminal signal functionally equivalent to that of PE25. Exchange of these C-terminal secretion signals between the PE proteins restored secretion, but each PE protein remained secreted via its own ESX secretion system, indicating that an additional signal(s) provides system specificity. Remarkably, the YxxxD/E motif was also present in and required for efficient secretion of the ESX-1 substrates CFP-10 and EspB. Therefore, our data show that the YxxxD/E motif is a general secretion signal that is present in all known mycobacterial T7S substrates or substrate complexes.

Cyanovirin-N inhibits mannose-dependent Mycobacterium-C-type lectin interactions but does not protect against murine tuberculosis.

Cyanovirin-N (CV-N) is a mannose-binding lectin that inhibits HIV-1 infection by blocking mannose-dependent target cell entry via C-type lectins. Like HIV-1, Mycobacterium tuberculosis expresses mannosylated surface structures and exploits C-type lectins to gain cell access. In this study, we investigated whether CV-N, like HIV-1, can inhibit M. tuberculosis infection. We found that CV-N specifically interacted with mycobacteria by binding to the mannose-capped lipoglycan lipoarabinomannan. Furthermore, CV-N competed with the C-type lectins DC-SIGN and mannose receptor for ligand binding and inhibited the binding of M. tuberculosis to dendritic cells but, unexpectedly, not to macrophages. Subsequent in vivo infection experiments in a mouse model demonstrated that, despite its activity, CV-N did not inhibit or delay M. tuberculosis infection. This outcome argues against a critical role for mannose-dependent C-type lectin interactions during the initial stages of murine M. tuberculosis infection and suggests that, depending on the circumstances, M. tuberculosis can productively infect cells using different modes of entry.

Extended-spectrum ß-lactamase-producing Escherichia coli from retail chicken meat and humans: comparison of strains, plasmids, resistance genes, and virulence factors.

BACKGROUND: The worldwide prevalence of extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae is increasing rapidly both in hospitals and in the community. A connection between ESBL-producing bacteria in food animals, retail meat, and humans has been suggested. We previously reported on the genetic composition of a collection of ESBL-producing Escherichia coli (ESBL-EC) from chicken meat and humans from a restricted geographic area. Now, we have extended the analysis with plasmid replicons, virulence factors, and highly discriminatory genomic profiling methods. METHODS: One hundred forty-five ESBL-EC isolates from retail chicken meat, human rectal carriers, and blood cultures were analyzed using multilocus sequence typing, phylotyping, ESBL genes, plasmid replicons, virulence genes, amplified fragment length polymorphism (AFLP), and pulsed-field gel electrophoresis (PFGE). RESULTS: Three source groups overlapped substantially when their genetic composition was compared. A combined analysis using all variables yielded the highest resolution (Wilks lambda [Λ]: 0.08). Still, a prediction model based on the combined data classified 40% of the human isolates as chicken meat isolates. AFLP and PFGE showed that the isolates from humans and chicken meat could not be segregated and identified 1 perfect match between humans and chicken meat. CONCLUSIONS: We found significant genetic similarities among ESBL-EC isolates from chicken meat and humans according to mobile resistance elements, virulence genes, and genomic backbone. Therefore, chicken meat is a likely contributor to the recent emergence of ESBL-EC in human infections in the study region. This raises serious food safety questions regarding the abundant presence of ESBL-EC in chicken meat.

Emergence of colistin resistance in Enterobacteriaceae after the introduction of selective digestive tract decontamination in an intensive care unit.

Selective decontamination of the digestive tract (SDD) selectively eradicates aerobic Gram-negative bacteria (AGNB) by the enteral administration of oral nonabsorbable antimicrobial agents, i.e., colistin and tobramycin. We retrospectively investigated the impact of SDD, applied for 5 years as part of an infection control program for the control of an outbreak with extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae in an intensive care unit (ICU), on resistance among AGNB. Colistin MICs were determined on stored ESBL-producing K. pneumoniae isolates using the Etest. The occurrence of both tobramycin resistance among pathogens intrinsically resistant to colistin (CIR) and bacteremia caused by ESBL-producing K. pneumoniae and CIR were investigated. Of the 134 retested ESBL-producing K. pneumoniae isolates, 28 were isolated before SDD was started, and all had MICs of <1.5 mg/liter. For the remaining 106 isolated after starting SDD, MICs ranged between 0.5 and 24 mg/liter. Tobramycin-resistant CIR isolates were found sporadically before the introduction of SDD, but their prevalence increased immediately afterward. Segmented regression analysis showed a highly significant relationship between SDD and resistance to tobramycin. Five patients were identified with bacteremia caused by ESBL-producing K. pneumoniae before SDD and 9 patients thereafter. No bacteremia caused by CIR was found before SDD, but its occurrence increased to 26 after the introduction of SDD. In conclusion, colistin resistance among ESBL-producing K. pneumoniae isolates emerged rapidly after SDD. In addition, both the occurrence and the proportion of tobramycin resistance among CIR increased under the use of SDD. SDD should not be applied in outbreak settings when resistant bacteria are prevalent.

Preventing surgical-site infections in nasal carriers of Staphylococcus aureus.

BACKGROUND: Nasal carriers of Staphylococcus aureus are at increased risk for health care-associated infections with this organism. Decolonization of nasal and extranasal sites on hospital admission may reduce this risk. METHODS: In a randomized, double-blind, placebo-controlled, multicenter trial, we assessed whether rapid identification of S. aureus nasal carriers by means of a real-time polymerase-chain-reaction (PCR) assay, followed by treatment with mupirocin nasal ointment and chlorhexidine soap, reduces the risk of hospital-associated S. aureus infection. RESULTS: From October 2005 through June 2007, a total of 6771 patients were screened on admission. A total of 1270 nasal swabs from 1251 patients were positive for S. aureus. We enrolled 917 of these patients in the intention-to-treat analysis, of whom 808 (88.1%) underwent a surgical procedure. All the S. aureus strains identified on PCR assay were susceptible to methicillin and mupirocin. The rate of S. aureus infection was 3.4% (17 of 504 patients) in the mupirocin-chlorhexidine group, as compared with 7.7% (32 of 413 patients) in the placebo group (relative risk of infection, 0.42; 95% confidence interval [CI], 0.23 to 0.75). The effect of mupirocin-chlorhexidine treatment was most pronounced for deep surgical-site infections (relative risk, 0.21; 95% CI, 0.07 to 0.62). There was no significant difference in all-cause in-hospital mortality between the two groups. The time to the onset of nosocomial infection was shorter in the placebo group than in the mupirocin-chlorhexidine group (P=0.005). CONCLUSIONS: The number of surgical-site S. aureus infections acquired in the hospital can be reduced by rapid screening and decolonizing of nasal carriers of S. aureus on admission. (Current Controlled Trials number, ISRCTN56186788.)

Incidence of infection with multidrug-resistant Gram-negative bacteria and vancomycin-resistant enterococci in carriers: a systematic review and meta-regression analysis.

BACKGROUND: Carriers of multidrug-resistant bacteria are at risk of infections with these bacteria; the precise size of this risk is unclear. We aimed to quantify the effect of gut colonisation on subsequent risk of infection with multidrug-resistant bacteria. METHODS: We performed a systematic review and meta-regression analysis. We searched PubMed, Embase, Web of Science Core Collection, and Google Scholar for follow-up studies published from Jan 1, 1995, to March 17, 2022, that measured the incidence of infections with multidrug-resistant Gram-negative bacteria (MDR-GNB) and from Jan 1, 1995, to March 15, 2022, that measured the incidence of infections with vancomycin-resistant enterococci (VRE). We included original cohort studies and case-control studies that used incidence-density sampling, included 50 or more patients with enteric colonisation or positive urinary samples as a surrogate marker of colonisation, or both, and analysed infections clearly preceded by colonisation. We did not use any language restrictions. We excluded studies not reporting length of follow-up. Summary data were extracted and independently cross-verified by two authors. Carriage was defined as MDR-GNB or VRE, detected in faecal or urinary cultures. Our primary outcomes were cumulative incidence and incidence density of infection in patients colonised by multidrug-resistant bacteria. To estimate pooled incidences, general linearised mixed-effects meta-regressions were used, adjusting for varying follow-up durations. This study is registered with PROSPERO, CRD42020222415. FINDINGS: Of the 301 studies identified, 44 studies (26 on MDR-GNB, 14 on VRE, and four on both MDR-GNB and VRE) from 14 countries were retained for qualitative synthesis, 40 of which were analysed with meta-regression, comprising data for 14 049 patients colonised with multidrug-resistant bacteria. The pooled cumulative incidence of infection was 14% (95% CI 10-18; p<0·0001) at a median follow-up time of 30 days for MDR-GNB (845 cases of infection in 9034 patients colonised) and 8% (5-13; p<0·0001) at 30 days for VRE (229 cases of infection in 4747 patients colonised). Infection incidence density (4·26 infections per 1000 patient-days; 95% CI 1·69-6·82) and cumulative incidence of infection (19%, 95% CI 15-25; p<0·0001; 602 cases of infection in 4547 patients colonised) were highest for carbapenem-resistant Gram-negative bacteria at 30 days. Risk of bias was rated low to moderate. INTERPRETATION: The risk of infection was substantial, with the highest risk for patients colonised with carbapenem-resistant Gram-negative bacteria and the lowest in patients with VRE. These data might help to guide prophylactic and treatment decisions and form a valuable resource for planning clinical trials on targeted prevention. FUNDING: The Netherlands Organization for Health Research and Development.