Search

Staphylococcus aureusis one of the most virulent bacteria and frequently causes prosthetic joint infections.

Antibiotic resistance genes evolve in the environment, in animals, and in humans; strategic action is needed on all three fronts to help understand resistance and to limit its spread.

Limited information is available on whether blaKPC-containing plasmids from isolates in a hospital outbreak can be differentiated from epidemiologically unrelated blaKPC-containing plasmids based on sequence data. This study aimed to evaluate the performance of three approaches to distinguish epidemiologically related from unrelated blaKPC-containing pKpQiL-like IncFII(k2)-IncFIB(pQiL) plasmids.

AbstractObjective:The epidemiology of ESBL-producing Enterobacteriaceae (ESBL-PE) has been extensively studied in hospitals, but data on community transmission are scarce. We investigated ESBL-PE cocarriage and acquisition in households using a systematic literature review.Methods:We conducted a systematic literature search to retrieve cross-sectional or cohort studies published between 1990 and 2018 evaluating cocarriage proportions and/or acquisition rates of ESBL-PE among household members, without language restriction. We excluded studies focusing on animal-to-human transmission or conducted in nonhousehold settings. The main outcomes were ESBL-PE cocarriage proportions and acquisition rates, stratified according to phenotypic or genotypic assessment of strain relatedness. Cocarriage proportions of clonally related ESBL-PE were transformed using the double-arcsine method and were pooled using a random-effects model. Potential biases were assessed manually.Results:We included 13 studies. Among 863 household members of ESBL-PE positive index cases, prevalence of ESBL-PE cocarriage ranged from 8% to 37%. Overall, 12% (95% confidence interval [CI], 8%–16%) of subjects had a clonally related strain. Those proportions were higher for Klebsiella pneumoniae(20%–25%) than for Escherichia coli(10%–20%). Acquisition rates of clonally related ESBL-PE among 180 initially ESBL-PE–free household members of a previously identified carrier ranged between 1.56 and 2.03 events per 1,000 person weeks of follow-up. We identified multiple sources of bias and high heterogeneity (I2, 70%) between studies.Conclusions:ESBL-PE household cocarriage is frequent, suggesting intrafamilial acquisition. Further research is needed to evaluate the risk and control of ESBL-PE household transmission.

AbstractObjective:Automated surveillance of healthcare-associated infections reduces workload and improves standardization, but it has not yet been adopted widely. In this study, we assessed the performance and feasibility of an easy implementable framework to develop algorithms for semiautomated surveillance of deep incisional and organ-space surgical site infections (SSIs) after orthopedic, cardiac, and colon surgeries.Design:Retrospective cohort study in multiple countries.Methods:European hospitals were recruited and selected based on the availability of manual SSI surveillance data from 2012 onward (reference standard) and on the ability to extract relevant data from electronic health records. A questionnaire on local manual surveillance and clinical practices was administered to participating hospitals, and the information collected was used to pre-emptively design semiautomated surveillance algorithms standardized for multiple hospitals and for center-specific application. Algorithm sensitivity, positive predictive value, and reduction of manual charts requiring review were calculated. Reasons for misclassification were explored using discrepancy analyses.Results:The study included 3 hospitals, in the Netherlands, France, and Spain. Classification algorithms were developed to indicate procedures with a high probability of SSI. Components concerned microbiology, prolonged length of stay or readmission, and reinterventions. Antibiotics and radiology ordering were optional. In total, 4,770 orthopedic procedures, 5,047 cardiac procedures, and 3,906 colon procedures were analyzed. Across hospitals, standardized algorithm sensitivity ranged between 82% and 100% for orthopedic surgery, between 67% and 100% for cardiac surgery, and between 84% and 100% for colon surgery, with 72%–98% workload reduction. Center-specific algorithms had lower sensitivity.Conclusions:Using this framework, algorithms for semiautomated surveillance of SSI can be successfully developed. The high performance of standardized algorithms holds promise for large-scale standardization.

AbstractTo reduce the of risk infection after colorectal surgery, oral antibiotic preparation (OAP) and mechanical bowel preparation (MBP) can be applied. Whether OAP can be used without MBP is unclear. A meta-analysis of observational studies demonstrated comparable effectiveness of OAP with and without MBP regarding SSI risk.

AbstractObjective:Surveillance of surgical site infections (SSIs) is important for infection control and is usually performed through retrospective manual chart review. The aim of this study was to develop an algorithm for the surveillance of deep SSIs based on clinical variables to enhance efficiency of surveillance.Design:Retrospective cohort study (2012–2015).Setting:A Dutch teaching hospital.Participants:We included all consecutive patients who underwent colorectal surgery excluding those with contaminated wounds at the time of surgery. All patients were evaluated for deep SSIs through manual chart review, using the Centers for Disease Control and Prevention (CDC) criteria as the reference standard.Analysis:We used logistic regression modeling to identify predictors that contributed to the estimation of diagnostic probability. Bootstrapping was applied to increase generalizability, followed by assessment of statistical performance and clinical implications.Results:In total, 1,606 patients were included, of whom 129 (8.0%) acquired a deep SSI. The final model included postoperative length of stay, wound class, readmission, reoperation, and 30-day mortality. The model achieved 68.7% specificity and 98.5% sensitivity and an area under the receiver operator characteristic (ROC) curve (AUC) of 0.950 (95% CI, 0.932–0.969). Positive and negative predictive values were 21.5% and 99.8%, respectively. Applying the algorithm resulted in a 63.4% reduction in the number of records requiring full manual review (from 1,606 to 590).Conclusions:This 5-parameter model identified 98.5% of patients with a deep SSI. The model can be used to develop semiautomatic surveillance of deep SSIs after colorectal surgery, which may further improve efficiency and quality of SSI surveillance.

BACKGROUNDExtended-spectrum β-lactamase–producing Enterobacteriaceae (ESBL-E) are emerging worldwide. Contact precautions are recommended for known ESBL-E carriers to control the spread of ESBL-E within hospitals.OBJECTIVEThis study quantified the acquisition of ESBL-E rectal carriage among patients in Dutch hospitals, given the application of contact precautions.METHODSData were used from 2 cluster-randomized studies on isolation strategies for ESBL-E: (1) the SoM study, performed in 14 Dutch hospitals from 2011 through 2014 and (2) the R-GNOSIS study, for which data were limited to those collected in a Dutch hospital in 2014. Perianal cultures were obtained, either during ward-based prevalence surveys (SoM), or at admission and twice weekly thereafter (R-GNOSIS). In both studies, contact precautions were applied to all known ESBL-E carriers. Estimates for acquisition of ESBL-E were based on the results of admission and discharge cultures from patients hospitalized for more than 2 days (both studies) and a Markov chain Monte Carlo (MCMC) model, applied to all patients hospitalized (R-GNOSIS).RESULTSThe absolute risk of acquisition of ESBL-E rectal carriage ranged from 2.4% to 2.9% with an ESBL-E acquisition rate of 2.8 to 3.8 acquisitions per 1,000 patient days. In addition, 28% of acquisitions were attributable to patient-dependent transmission, and the per-admission reproduction number was 0.06.CONCLUSIONSThe low ESBL-E acquisition rate in this study demonstrates that it is possible to control the nosocomial transmission of ESBL in a low-endemic, non-ICU setting where Escherichia coliis the most prevalent ESBL-E and standard and contact precautions are applied for known ESBL-E carriers.TRIAL REGISTRATIONNederlands Trialregister, NTR2799, http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2799; ISRCTN Registry, ISRCTN57648070, http://www.isrctn.com/ISRCTN57648070Infect Control Hosp Epidemiol2018;39:32–39

IMPORTANCE: The human and financial costs of treating surgical site infections (SSIs) are increasing. The number of surgical procedures performed in the United States continues to rise, and surgical patients are initially seen with increasingly complex comorbidities. It is estimated that approximately half of SSIs are deemed preventable using evidence-based strategies. OBJECTIVE: To provide new and updated evidence-based recommendations for the prevention of SSI. EVIDENCE REVIEW: A targeted systematic review of the literature was conducted in MEDLINE, EMBASE, CINAHL, and the Cochrane Library from 1998 through April 2014. A modified Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach was used to assess the quality of evidence and the strength of the resulting recommendation and to provide explicit links between them. Of 5759 titles and abstracts screened, 896 underwent full-text review by 2 independent reviewers. After exclusions, 170 studies were extracted into evidence tables, appraised, and synthesized. FINDINGS: Before surgery, patients should shower or bathe (full body) with soap (antimicrobial or nonantimicrobial) or an antiseptic agent on at least the night before the operative day. Antimicrobial prophylaxis should be administered only when indicated based on published clinical practice guidelines and timed such that a bactericidal concentration of the agents is established in the serum and tissues when the incision is made. In cesarean section procedures, antimicrobial prophylaxis should be administered before skin incision. Skin preparation in the operating room should be performed using an alcohol-based agent unless contraindicated. For clean and clean-contaminated procedures, additional prophylactic antimicrobial agent doses should not be administered after the surgical incision is closed in the operating room, even in the presence of a drain. Topical antimicrobial agents should not be applied to the surgical incision. During surgery, glycemic control should be implemented using blood glucose target levels less than 200 mg/dL, and normothermia should be maintained in all patients. Increased fraction of inspired oxygen should be administered during surgery and after extubation in the immediate postoperative period for patients with normal pulmonary function undergoing general anesthesia with endotracheal intubation. Transfusion of blood products should not be withheld from surgical patients as a means to prevent SSI. CONCLUSIONS AND RELEVANCE: This guideline is intended to provide new and updated evidence-based recommendations for the prevention of SSI and should be incorporated into comprehensive surgical quality improvement programs to improve patient safety.

ABSTRACTResistance to methicillin in Staphylococcus aureusis caused primarily by the mecAgene, which is carried on a mobile genetic element, the staphylococcal cassette chromosome mec(SCCmec). Horizontal transfer of this element is supposed to be an important factor in the emergence of new clones of methicillin-resistant Staphylococcus aureus(MRSA) but has been rarely observed in real time. In 2012, an outbreak occurred involving a health care worker (HCW) and three patients, all carrying a fusidic acid-resistant MRSA strain. The husband of the HCW was screened for MRSA carriage, but only a methicillin-susceptible S. aureus(MSSA) strain, which was also resistant to fusidic acid, was detected. Multiple-locus variable-number tandem-repeat analysis (MLVA) typing showed that both the MSSA and MRSA isolates were MT4053-MC0005. This finding led to the hypothesis that the MSSA strain acquired the SCCmecand subsequently caused an outbreak. To support this hypothesis, next-generation sequencing of the MSSA and MRSA isolates was performed. This study showed that the MSSA isolate clustered closely with the outbreak isolates based on whole-genome multilocus sequence typing and single-nucleotide polymorphism (SNP) analysis, with a genetic distance of 17 genes and 44 SNPs, respectively. Remarkably, there were relatively large differences in the mobile genetic elements in strains within and between individuals. The limited genetic distance between the MSSA and MRSA isolates in combination with a clear epidemiologic link supports the hypothesis that the MSSA isolate acquired a SCCmecand that the resulting MRSA strain caused an outbreak.

ABSTRACTIn the Netherlands, the number of cases of infection with New Delhi metallo-beta-lactamase (NDM)-positive Enterobacteriaceaeis low. Here, we report an outbreak of NDM-1-producing Klebsiella pneumoniaeinfection in a Dutch hospital with interspecies transfer of the resistance plasmid and unexpected occurrence in other unrelated health care centers (HCCs). Next-generation sequencing was performed on 250 carbapenemase-producing Enterobacteriaceaeisolates, including 42 NDM-positive isolates obtained from 29 persons at the outbreak site. Most outbreak isolates were K. pneumoniae(n= 26) and Escherichia coli(n= 11), but 5 isolates comprising three other Enterobacteriaceaespecies were also cultured. The 26 K. pneumoniaeisolates had sequence type 873 (ST873), as did 7 unrelated K. pneumoniaeisolates originating from five geographically dispersed HCCs. The 33 ST873 isolates that clustered closely together using whole-genome multilocus sequence typing (wgMLST) carried the same plasmids and had limited differences in the resistome. The 11 E. colioutbreak isolates showed great variety in STs, did not cluster using wgMLST, and showed considerable diversity in resistome and plasmid profiles. The blaNDM-1gene-carrying plasmid present in the ST873 K. pneumoniaeisolates was found in all the other Enterobacteriaceaespecies cultured at the outbreak location and in a single E. coliisolate from another HCC. We describe a hospital outbreak with an NDM-1-producing K. pneumoniaestrain from an unknown source that was also found in patients from five other Dutch HCCs in the same time frame without an epidemiological link. Interspecies transfer of the resistance plasmid was observed in other Enterobacteriaceaespecies isolated at the outbreak location and in another HCC.

ABSTRACTMolecular 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 Citrobacterspp., the Enterobacter cloacaecomplex, Escherichia coli, Klebsiella oxytoca, and Klebsiella pneumoniaeand 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 Citrobacterspp., the E. cloacaecomplex, E. coli, and K. pneumoniae. wgMLST was shown to have higher discriminatory power and typeability than in silicoMLST. 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.

Livestock-associated methicillin-resistant Staphylococcus aureus(LA-MRSA) is highly prevalent in pigs and veal calves. The environment and air in pig and veal calf barns is often contaminated with LA-MRSA, and can act as a transmission source for humans. This study explores exposure–response relationships between sequence type 398 (ST398) MRSA air exposure level and nasal ST398 MRSA carriage in people working and/or living on farms. Samples and data were used from three longitudinal field studies in pig and veal calf farm populations. Samples consisted of nasal swabs from the human participants and electrostatic dust fall collectors capturing airborne settled dust in barns. In both multivariate and mutually adjusted analyses, a strong association was found between nasal ST398 MRSA carriage in people working in the barns for >20?h per week and MRSA air levels. In people working in the barns < 20?h per week there was a strong association between nasal carriage and number of working hours. Exposure to ST398 MRSA in barn air seems to be an important determinant for nasal carriage, especially in the highly exposed group of farmers, next to duration of contact with animals. Intervention measures should therefore probably also target reduction of ST398 MRSA air levels.

OBJECTIVERisk factors for rectal carriage of ESBL-E and transmission were investigated in an outbreak of extended-spectrum ß-lactamase–producing Enterobacteriaceae (ESBL-E).DESIGNRectal carriage of ESBL-E was determined in a cross-sectional survey by culture of perianal swabs or fecal samples. Both phenotypical and genotypical methods were used to detect the production of ESBL. Nosocomial transmission was defined as the presence of genotypically related strains in =2 residents within the NH. Patient characteristics and variables in infection control practices were registered to investigate risk factors for transmission.SETTINGA nursing home (NH) in the southern Netherlands.PARTICIPANTSOf 189 residents, 160 residents (84.7%) were screened for ESBL-E carriage. Of these 160 residents, 33 (20.6%) were ESBL-E positive. ESBL carriage rates varied substantially between wards (range, 0–47%). Four different ESBL-E clusters were observed. A blaCTX-M1-15positive E. coliST131 constituted the largest cluster (n=21) and was found in multiple wards (n=7).RESULTSOur investigation revealed extensive clonal dissemination of blaCTX-M1-15-positive E. coliST131 in a nursing home. Unexplained differences in ESBL prevalence were detected among the wards.CONCLUSIONSAs NHs constitute potential sources of multidrug-resistant bacteria, it is important to gain a better understanding of the risks factors and routes of transmission of ESBL-E.Infect Control Hosp Epidemiol 2014;00(0): 1–7

Macrolide resistance is an increasing problem; there is therefore debate about when to implement maintenance treatment with macrolides in patients with chronic obstructive pulmonary disease (COPD). We aimed to investigate whether patients with COPD who had received treatment for three or more exacerbations in the previous year would have a decrease in exacerbation rate when maintenance treatment with azithromycin was added to standard care.

Objective.Determine the prevalence of extended-spectrum β-lactamase (ESBL)–producing Enterobacteriaceae (ESBL-PE) contamination of food and colonization of food handlers in a hospital kitchen and compare retrieved ESBL-PE strains with patient isolates.Design.Cross-sectional study.Setting.A 2,200-bed tertiary care university hospital in Switzerland.Participants.Food handlers.Methods.Raw and prepared food samples were obtained from the hospital kitchen, with a comparator group from local supermarkets. Fecal samples collected from food handlers and selectively pre-enriched homogenized food samples were inoculated onto selective chromogenic media. Phenotypic confirmation of ESBL production was performed using the double disk method. Representative ESBL-PE were characterized using polymerase chain reaction (PCR) and sequencing for blaCTX-M, blaSHV, and blaTEMgenes, and Escherichia colistrains were typed using phylotyping, repetitive element palindromic PCR, and multilocus sequence typing. Meat samples were screened for antibiotic residues using liquid chromatography time-of-flight mass spectrometry.Results.Sixty (92%) of the raw chicken samples were ESBL-PE positive, including 30 (86%) of the hospital samples and all supermarket samples. No egg, beef, rabbit, or cooked chicken samples were ESBL-PE positive. No antibiotic residues were detected. Six (6.5%) of 93 food handlers were ESBL-PE carriers. ESBL-PE strains from chicken meat more commonly possessed blaCTX-M-1and blaCTX-M-2, whereas blaCTX-M-14and blaCTX-M-15were predominant among strains of human origin. There was partial overlap in the sequence type of E. colistrains of chicken and human origin. No E. coliST131 strains or blaCTX-M-15genes were isolated from meat.Conclusions.Although there is significant ESBL-PE contamination of delivered chicken meat, current preventive strategies minimize risks to food handlers, hospital staff, and patients.

Chronic obstructive pulmonary disease (COPD) is one of the major health problems in the world. Long-term treatment with macrolide antibiotics is a recent development that has been reported to have beneficial effects on exacerbation frequency. These effects are not only attributed to the antimicrobial effect but also to the immune modulatory effect. Six randomized trials and 1 retrospective study have been performed to investigate the efficacy of macrolides in the prevention of acute exacerbations of COPD. Besides the beneficial effects on the occurrence of exacerbations of COPD, this treatment also seems to improve quality of life and is well tolerated. Antimicrobial resistance is one of the future issues to consider before implementing this therapy.

ABSTRACTSelective 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 pneumoniaein an intensive care unit (ICU), on resistance among AGNB. Colistin MICs were determined on stored ESBL-producing K. pneumoniaeisolates using the Etest. The occurrence of both tobramycin resistance among pathogens intrinsically resistant to colistin (CIR) and bacteremia caused by ESBL-producing K. pneumoniaeand CIR were investigated. Of the 134 retested ESBL-producing K. pneumoniaeisolates, 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. pneumoniaebefore 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. pneumoniaeisolates 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.

ABSTRACTWe studied clinical characteristics, appropriateness of initial antibiotic treatment, and other factors associated with day 30 mortality in patients with bacteremia caused by extended-spectrum-β-lactamase (ESBL)-producing bacteria in eight Dutch hospitals. Retrospectively, information was collected from 232 consecutive patients with ESBL bacteremia (due to Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae) between 2008 and 2010. In this cohort (median age of 65 years; 24 patients were <18 years of age), many had comorbidities, such as malignancy (34%) or recurrent urinary tract infection (UTI) (15%). One hundred forty episodes (60%) were nosocomial, 54 (23%) were otherwise health care associated, and 38 (16%) were community acquired. The most frequent sources of infection were UTI (42%) and intra-abdominal infection (28%). Appropriate therapy within 24 h after bacteremia onset was prescribed to 37% of all patients and to 54% of known ESBL carriers. The day 30 mortality rate was 20%. In a multivariable analysis, a Charlson comorbidity index of ≥3, an age of ≥75 years, intensive care unit (ICU) stay at bacteremia onset, a non-UTI bacteremia source, and presentation with severe sepsis, but not inappropriate therapy within <24 h (adjusted odds ratio [OR], 1.53; 95% confidence interval [CI], 0.68 to 3.45), were associated with day 30 mortality. Further assessment of confounding and a stratified analysis for patients with UTI and non-UTI origins of infection did not reveal a statistically significant effect of inappropriate therapy on day 30 mortality, and these results were insensitive to the possible misclassification of patients who had received β-lactam–β-lactamase inhibitor combinations or ceftazidime as initial treatment. In conclusion, ESBL bacteremia occurs mostly in patients with comorbidities requiring frequent hospitalization, and 84% of episodes were health care associated. Factors other than inappropriate therapy within <24 h determined day 30 mortality.

This review discusses the relevant studies on selective decontamination of the digestive tract (SDD) published between 2009 and mid-2011.

Two previous studies in tertiary care hospitals identified Staphylococcus aureuscolonization of intravascular (IV) catheters as a strong predictor of subsequent S. aureusbacteremia (SAB), even in the absence of clinical signs of systemic infection. Bacteremia was effectively prevented by timely antibiotic therapy. We conducted this study to corroborate the validity of these findings in non-university hospitals.

ABSTRACTThe prevalence of methicillin-resistant Staphylococcus aureus(MRSA) carriage in pig and veal calf farmers in the Netherlands is estimated at 25 to 35%. However, no information is available about MRSA carriage in humans after short-term occupational exposure to pigs or veal calves. This study examines the prevalence and duration of MRSA acquisition after short-term intensive exposure to pigs or veal calves for persons not exposed to livestock on a daily basis. The study was performed with field workers who took samples from the animals or the animal houses in studies on MRSA prevalence in pig and veal farms. They were tested for MRSA by taking nasal samples before, directly after, and 24 h after they visited the farms. There were 199 sampling moments from visits to 118 MRSA-positive farms. Thirty-four of these visits (17%) resulted in the acquisition of MRSA. Thirty-one persons (94%) appeared negative again after 24 h. There were 62 visits to 34 MRSA-negative farms; none of the field workers acquired MRSA during these visits. Except for that from one person, all spatypes found in the field workers were identical to those found in the animals or in the dust in animal houses and belonged to the livestock-associated clone. In conclusion, MRSA is frequently present after short-term occupational exposure, but in most cases the strain is lost again after 24 h.

ABSTRACTThe objectives of the present study were to determine the effects of multiple targeted interventions on the level of use of quinolones and the observed rates of resistance to quinolones in Escherichia coliisolates from hospitalized patients. A bundle consisting of four interventions to improve the use of quinolones was implemented. The outcome was measured from the monthly levels of use of intravenous (i.v.) and oral quinolones and the susceptibility patterns for E. coliisolates from hospitalized patients. Statistical analyses were performed using segmented regression analysis and segmented Poisson regression models. Before the bundle was implemented, the annual use of quinolones was 2.7 defined daily doses (DDDs)/100 patient days. After the interventions, in 2007, this was reduced to 1.7 DDDs/100 patient days. The first intervention, a switch from i.v. to oral medication, was associated with a stepwise reduction in i.v. quinolone use of 71 prescribed daily doses (PDDs) per month (95% confidence interval [CI] = 47 to 95 PDDs/month, P< 0.001). Intervention 2, introduction of a new antibiotic guideline and education program, was associated with a stepwise reduction in the overall use of quinolones (reduction, 107 PDDs/month [95% CI = 58 to 156 PDDs/month). Before the interventions the quinolone resistance rate was increasing, on average, by 4.6% (95% CI = 2.6 to 6.1%) per year. This increase leveled off, which was associated with intervention 2 and intervention 4, active monitoring of prescriptions and feedback. Trends in resistance to other antimicrobial agents did not change. This study showed that the hospital-wide use of quinolones can be significantly reduced by an active policy consisting of multiple interventions. There was also a stepwise reduction in the rate of quinolone resistance associated with the bundle of interventions.

Integrons play an important role in the dissemination of resistance genes among bacteria. Nearly 70% of highly resistant gram-negative bacteria isolated at a tertiary care hospital harbored an integron. Epidemiologic analysis suggests that horizontal gene transfer is an important mechanism of resistance spread and has a greater contribution than cross-transmission to levels of resistance in settings where highly resistant gram-negative bacteria are endemic.

ObjectiveTo assess the performance of rapid antigen tests with unsupervised nasal and combined oropharyngeal and nasal self-sampling during the omicron period.DesignProspective cross sectional diagnostic test accuracy study.SettingThree public health service covid-19 test sites in the Netherlands, 21 December 2021 to 10 February 2022.Participants6497 people with covid-19 symptoms aged ≥16 years presenting for testing.InterventionsParticipants had a swab sample taken for reverse transcription polymerase chain reaction (RT-PCR, reference test) and received one rapid antigen test to perform unsupervised using either nasal self-sampling (during the emergence of omicron, and when omicron accounted for >90% of infections, phase 1) or with combined oropharyngeal and nasal self-sampling in a subsequent (phase 2; when omicron accounted for >99% of infections). The evaluated tests were Flowflex (Acon Laboratories; phase 1 only), MPBio (MP Biomedicals), and Clinitest (Siemens-Healthineers).Main outcome measuresThe main outcomes were sensitivity, specificity, and positive and negative predictive values of each self-test, with RT-PCR testing as the reference standard.ResultsDuring phase 1, 45.0% (n=279) of participants in the Flowflex group, 29.1% (n=239) in the MPBio group, and 35.4% ((n=257) in the Clinitest group were confirmatory testers (previously tested positive by a self-test at own initiative). Overall sensitivities with nasal self-sampling were 79.0% (95% confidence interval 74.7% to 82.8%) for Flowflex, 69.9% (65.1% to 74.4%) for MPBio, and 70.2% (65.6% to 74.5%) for Clinitest. Sensitivities were substantially higher in confirmatory testers (93.6%, 83.6%, and 85.7%, respectively) than in those who tested for other reasons (52.4%, 51.5%, and 49.5%, respectively). Sensitivities decreased from 87.0% to 80.9% (P=0.16 by χ2test), 80.0% to 73.0% (P=0.60), and 83.1% to 70.3% (P=0.03), respectively, when transitioning from omicron accounting for 29% of infections to >95% of infections. During phase 2, 53.0% (n=288) of participants in the MPBio group and 44.4% (n=290) in the Clinitest group were confirmatory testers. Overall sensitivities with combined oropharyngeal and nasal self-sampling were 83.0% (78.8% to 86.7%) for MPBio and 77.3% (72.9% to 81.2%) for Clinitest. When combined oropharyngeal and nasal self-sampling was compared with nasal self-sampling, sensitivities were found to be slightly higher in confirmatory testers (87.4% and 86.1%, respectively) and substantially higher in those testing for other reasons (69.3% and 59.9%, respectively).ConclusionsSensitivities of three rapid antigen tests with nasal self-sampling decreased during the emergence of omicron but was only statistically significant for Clinitest. Sensitivities appeared to be substantially influenced by the proportion of confirmatory testers. Sensitivities of MPBio and Clinitest improved after the addition of oropharyngeal to nasal self-sampling. A positive self-test result justifies prompt self-isolation without the need for confirmatory testing. Individuals with a negative self-test result should adhere to general preventive measures because a false negative result cannot be ruled out. Manufacturers of MPBio and Clinitest may consider extending their instructions for use to include combined oropharyngeal and nasal self-sampling, and other manufacturers of rapid antigen tests should consider evaluating this as well.

•The NPA of the Xpert Xpress Flu/RSV was ≥99% for Influenza A/B virus and RSV•The PPA of the Xpert Xpress Flu/RSV was ≥92% for Influenza A/B virus and 88% for RSV•The lower PPA for RSV may be explained by a reduced ability to detect RSV-A

Objective.To determine the incidence density of highly resistant organisms (HROs) and the relative contribution of horizontal spread in a setting of endemicity.Methods.Prospective surveillance was performed among hospitalized patients during an 18-month period. Enterobacteriaceae, non-fermentative gram-negative bacilli, Staphylococcus aureus, Streptococcus pneumoniae,and Enterococcus faecium—all considered highly resistant, according to Dutch guidelines—were included. Epidemiological linkage and nosocomial transmission were determined on the basis of molecular typing and hospital admission data.Results.From 119 patients, we recovered a total of 170 unique HRO isolates, as follows: Escherichia coli,96 isolates; Klebsiellaspecies, 11 isolates; Enterobacterspecies, 8 isolates; Proteusspecies, 9 isolates; Citrobacterspecies, 5 isolates; Pseudomonasspecies, 5 isolates; Aci-netobacterspecies, 3 isolates; Morganellaspecies, 2 isolates; Salmonellaspecies, 1 isolate; Serratiaspecies, 1 isolate; S. pneumoniae,20 isolates; and S. aureus,9 isolates. No vancomycin-resistant E. faeciumwas found. The incidence density was 4.3 HRO isolates per 10,000 patient-days. The majority of HRO isolates were unique, and nosocomial transmission was observed 4 times for highly resistant gram-negative bacilli (case reproduction rate, 0.05) and 4 times for penicillin-nonsusceptible S. pneumoniae(case reproduction rate, 0.29). A stay on the intensive care unit was the main determinant for the recovery of an HRO.Conclusion.Nosocomial transmission of HROs was observed 8 times during the 18-month period. The intensive care unit was identified as the main reservoir of horizontal spread of HROs. This study shows that nosocomial transmission of HROs is largely preventable using transmission precautions.

The present review describes the literature about the prevention of Staphylococcus aureusinfections in surgery, published from August 2006 to January 2008, and puts it into perspective.

ABSTRACTThe main aim of our study was to determine the added value of PCR for the diagnosis of Legionnaires’ disease (LD) in routine clinical practice. The specimens were samples submitted for routine diagnosis of pneumonia from December 2002 to November 2005. Patients were evaluated if, in addition to PCR, the results of at least one of the following diagnostic tests were available: (i) culture for Legionellaspp. on buffered charcoal yeast extract agar or (ii) detection of Legionella pneumophilaantigen in urine specimens. Of the 151 evaluated patients, 37 (25%) fulfilled the European Working Group on Legionella Infections criteria for a confirmed case of LD (the “gold standard”). An estimated sensitivity, specificity, and overall percent agreement of 86% (32 of 37; 95% confidence interval [CI] = 72 to 95%), 95% (107 of 112; 95% CI = 90 to 98%), and 93% (139 of 149), respectively, were found for 16S rRNA-based PCR, and corresponding values of 92% (34 of 37; 95% CI = 78 to 98%), 98% (110 of 112; 95% CI = 93 to 100%), and 97% (144 of 149), respectively, were found for the mipgene-based PCR. A total of 35 patients were diagnosed by using the urinary antigen test, and 34 were diagnosed by the 16S rRNA-based PCR. With the mipgene PCR one more case of LD (n= 36; not significant) was detected. By combining urinary antigen test and the mipgene PCR, LD was diagnosed in an additional 4 (11%) patients versus the use of the urinary antigen test alone. The addition of a L. pneumophila-specific mipgene PCR to a urinary antigen test is useful in patients with suspected LD who produce sputum and might allow the early detection of a significant number of additional patients.

Objective.To evaluate the economic impact of performing rapid testing for Staphylococcus aureuscolonization before admission for all inpatients who are scheduled to undergo elective surgery and providing subsequent decolonization therapy for those patients found to be colonized with S. aureus.Methods.A budget impact model that used probabilistic sensitivity analysis to account for the uncertainties in the input variables was developed. Primary input variables included the marginal effect of S. aureusinfection on patient outcomes among patients who underwent elective surgery, patient demographic characteristics, the prevalence of nasal carriage of S. aureus,the sensitivity and specificity of the rapid diagnostic test for S. aureuscolonization, the efficacyof decolonization therapy for nasal carriage of S. aureus,and cost data. Data sources for the input variables included the 2003 Nationwide Inpatient Sample data and the published literature.Results.In 2003, there were an estimated 7,181,484 patients admitted to US hospitals for elective surgery. Our analysis indicated preadmission testing and subsequent decolonization therapy for patients colonized with S. aureuswould have produced a mean annual cost savings to US hospitals of $231,538,400 (95% confidence interval [CI], -$300 million to $1.3 billion). The mean annual number of hospital-days that could have been eliminated was estimated at 364,919 days (95% CI, 67,893-926,983 days), and a mean of 935 in-hospital deaths (95% CI, 88-3,691) could have been avoided per year. Sensitivity analysis indicated a 64.5% probability that there would be cost savings to US hospitals as a result of preadmission testing and subsequent decolonization therapy.Conclusion.The addition of preadmission testing and decolonization therapy to standard care would result in significant cost savings, even after accounting for variations in the model input values.

ABSTRACTIncreasing antibiotic resistance in gram-negative bacteria has recently renewed interest in colistin as a therapeutic option. The increasing use of colistin necessitates the availability of rapid and reliable methods for colistin susceptibility testing. We compared seven methods of colistin susceptibility testing (disk diffusion, agar dilution on Mueller-Hinton [MH] and Isosensitest agar, Etest on MH and Isosensitest agar, broth microdilution, and VITEK 2) on 102 clinical isolates collected from patient materials during a selective digestive decontamination or selective oral decontamination trial in an intensive-care unit. Disk diffusion is an unreliable method to measure susceptibility to colistin. High error rates and low levels of reproducibility were observed in the disk diffusion test. The colistin Etest, agar dilution, and the VITEK 2 showed a high level of agreement with the broth microdilution reference method. Heteroresistance for colistin was observed in six Enterobacter cloacaeisolates and in one Acinetobacter baumanniiisolate. This is the first report of heteroresistance to colistin in E. cloacaeisolates. Resistance to colistin in these isolates seemed to be induced upon exposure to colistin rather than being caused by stable mutations. Heteroresistant isolates could be detected in the broth microdilution, agar dilution, Etest, or disk diffusion test. The VITEK 2 displayed low sensitivity in the detection of heteroresistant subpopulations of E. cloacae. The VITEK 2 colistin susceptibility test can therefore be considered to be a reliable tool to determine susceptibility to colistin in isolates of genera that are known not to exhibit resistant subpopulations. In isolates of genera known to (occasionally) exhibit heteroresistance, an alternative susceptibility testing method capable of detecting heteroresistance should be used.

ABSTRACTPrudent use of antibiotics is mandatory to control antibiotic resistance. The objective of this study was to determine if prevalence surveys are useful tools to determine the appropriateness of antimicrobial therapy (AMT) and determinants of inappropriate AMT. The study was performed in a 1,350-bed teaching hospital including all medical specialities. Six consecutive 1-day prevalence surveys of in-patients were performed twice yearly from 2001 to 2004. Data on the demographics, infections, and AMT were gathered. The appropriateness of AMT was assessed according to a standardized algorithm based on the local AMT prescription guidelines. On average, 684 patients were included in each survey (total, 4,105). The use of AMT as determined in the prevalence survey corresponded to the annual data from the pharmacy department. Nine hundred thirty-eight (22.9%) of the patients received AMT, and in 351 (37.4%) of these patients AMT was inappropriate. Only 25 (0.6%) patients did not receive AMT, although it was indicated. After multivariate analysis, the use of quinolones was the only statistically significant variable associated with inappropriate use. Prevalence surveys proved to be useful tools to judge the appropriateness of AMT and to identify determinants of inappropriate use. This study shows that in a setting with a low use of AMT, there are few patients who inadvertently do not receive AMT. On the other hand, a substantial number of the patients are treated inappropriate.

Background:Central-line–associated bloodstream infections (CLABSIs) are serious complications of modern health care, leading to increased morbidity, mortality, and costs. Since 2012, a multimodal insertion and care bundle for central venous catheters (CVCs) has been implemented in the intensive care unit (ICU) of the Amphia Hospital Breda, The Netherlands. The implementation of this bundle was associated with sustainable low CLABSI rates (1 per 1,000 CVC days). There was no surveillance of CLABSI in the other departments of the hospital. Objectives:We implemented semiautomated surveillance for CLABSI in non-ICU inpatients. Methods:A single-center, retrospective study was conducted in a 1,370-bed teaching hospital in The Netherlands between January 2017 and December 2018. All hospitalized patients (aged ≥18 years) in non-ICU wards, with a CVC inserted, were screened for CLABSI. CLABSIs were diagnosed using the definitions of the national nosocomial surveillance network PREZIES, excluding infections already present on admission and secondary bloodstream infection. CLABSI rates were calculated as cases per 1,000 CVC days with 95% CIs. Results:In 2017, 14 CLABSI were reported during 4,656 CVC days (3.0 per 1,000 CVC days; 95% CI, 1.8–5.1). In 2018, 13 CLABSIs were reported during 4,995 catheter days (2.6 per 1,000 CVC days; 95% CI, 1.5–4.5). The mean duration of CVC days prior to CLABSI in 2017 and 2018 were 20 days (range, 4–28) and 14 days (range, 4–25), respectively. Most CLABSI events occurred in patients admitted to the hematology ward (13 of 27, 48.1%). Of those, 11 of 13 (84,6%) were patients with an acute myeloid leukemia (AML) and severe mucositis due to the intensive chemotherapy at the time of CLABSI. The remaining cases occurred in patients of 4 different surgical departments. Coagulase-negative staphylococci were the most common organisms recovered (25 of 27, 92.6%). Conclusions:To our knowledge, this is the first report of CLABSI-rates in non-ICU wards in the Netherlands. The CLABSI rates were higher in non-ICU wards compared to the ICU of our hospital. This difference was mainly because of the high CLABSI rate in the patients with AML.Funding:NoneDisclosures:None

Background:In The Netherlands, the national guidelines on Methicillin-Resistant Staphylococcus aureus(MRSA) prevention and control advocate screening of healthcare workers (HCWs) after unprotected exposure to MRSA carriers. Although this strategy is largely successful, contact tracing of staff is a time-consuming and costly component. We evaluated our contact tracing policy for HCWs over the years 2010–2018. Methods:A retrospective, observational study was performed in a Dutch teaching hospital. All HCWs who had unprotected contact with an MRSA carrier were included in contact tracing. When there had been a long period of unprotected admission prior to an MRSA finding, or when the index case was an HCW, the entire (nursing) team was tested. All samples of HCWs who were tested for MRSA carriage as part of contact tracing from 2010 until 2018 were included. A pooled nose, throat, and perineum swab was collected using the eSwab medium (Copan) and inoculated on chromID MRSA agar plates (bioMérieux) after enrichment in a broth. Molecular typing was performed using multiple-locus variable number of tandem repeat analysis (MLVA). Results:In total, we included 8,849 samples (range, 677–1,448 samples per year) from 287 contact tracings (range, 26–55 contact tracings per year). Overall, 32 HCWs were colonized with MRSA (0.36%; 95% CI, 0.26%–0.51%). None of them developed a clinical infection. Moreover, 8 HCWs (0.10%; 95% CI, 0.05%–0.19%) were colonized with the same MLVA type as the index case and were detected in 6 of 287 contact tracings (2%). In 4 of 8 of these cases, a positive HCW was the index for undertaking contact tracing. In 3 of 8 cases, it was clear that the HCW who was identified in the contact tracing was the source of the outbreak and was the cause of invasive MRSA infections in patients. Notably, a different MLVA type as the index case was found in 24 HCWs (0.27%; 95% CI, 0.18%–0.40%) of whom 7 of 24 HCWs (29.2%) were intermittent carriers. Conclusions:This study revealed a sustained low MRSA prevalence among samples in contact tracing of HCWs over 9 years. Furthermore, it shows that when MRSA contact tracing is performed according to the national guideline, only 1 of 1,000 samples results in a secondary case. This is similar to the population carriage rate of MRSA in The Netherlands. More frequently, an unrelated strain is found. These findings raise questions regarding the efficacy of the current strategy to perform contact tracing after unprotected exposure.Funding:NoneDisclosures:None

We evaluated the abilities of the Vircell immunoglobulin G (IgG) and IgM indirect immunofluorescence assay (IFA) for Legionella pneumophila serogroup 1, the IgM and IgG enzyme-linked immunosorbent assay (ELISA) for Legionella pneumophila serogroup 1, and the IgM-plus-IgG ELISA for Legionella pneumophila serogroups 1 to 6 to diagnose Legionnaires' disease (LD) in a well-described sample of patients with and without LD. Also, we determined the agreements, sensitivities, and specificities of the different Vircell assays in comparison to a validated ELISA (Serion classic ELISA). Clinical sensitivity and specificity were 74.6% and 96.6%, respectively, for the IgM IFA, 65.1% and 88.0% for the IgG IFA, 92.3% and 100% for the IgM ELISA, 43.3% and 96.6% for the IgG ELISA, and 90.8% and 100% for the IgM-plus-IgG ELISA. Compared to Serion classic ELISA, agreement, sensitivity, and specificity were 80.0%, 83.1%, and 78.4%, respectively, for the IgM IFA, 75.2%, 66.0%, and 79.5% for the IgG IFA, 89.5%, 82.0%, and 97.6% for the IgM ELISA, 81.9%, 88.9%, and 78.0% for the IgG ELISA, and 93.5%, 90.0%, and 96.6% for the IgM-plus-IgG ELISA. The value of a positive diagnostic result obtained by the Vircell IgM IFA, the Vircell IgG IFA, and the Vircell IgG ELISA might not be acceptable for a diagnostic assay. Both the high specificities and sensitivities of the Vircell IgM ELISA and the IgM-plus-IgG ELISA and the high correlation with the Serion classic ELISA indicate that they are useful in the diagnosis of LD.

ABSTRACTWe evaluated the abilities of the Vircell immunoglobulin G (IgG) and IgM indirect immunofluorescence assay (IFA) for Legionella pneumophilaserogroup 1, the IgM and IgG enzyme-linked immunosorbent assay (ELISA) for Legionella pneumophilaserogroup 1, and the IgM-plus-IgG ELISA for Legionella pneumophilaserogroups 1 to 6 to diagnose Legionnaires' disease (LD) in a well-described sample of patients with and without LD. Also, we determined the agreements, sensitivities, and specificities of the different Vircell assays in comparison to a validated ELISA (Serion classic ELISA). Clinical sensitivity and specificity were 74.6% and 96.6%, respectively, for the IgM IFA, 65.1% and 88.0% for the IgG IFA, 92.3% and 100% for the IgM ELISA, 43.3% and 96.6% for the IgG ELISA, and 90.8% and 100% for the IgM-plus-IgG ELISA. Compared to Serion classic ELISA, agreement, sensitivity, and specificity were 80.0%, 83.1%, and 78.4%, respectively, for the IgM IFA, 75.2%, 66.0%, and 79.5% for the IgG IFA, 89.5%, 82.0%, and 97.6% for the IgM ELISA, 81.9%, 88.9%, and 78.0% for the IgG ELISA, and 93.5%, 90.0%, and 96.6% for the IgM-plus-IgG ELISA. The value of a positive diagnostic result obtained by the Vircell IgM IFA, the Vircell IgG IFA, and the Vircell IgG ELISA might not be acceptable for a diagnostic assay. Both the high specificities and sensitivities of the Vircell IgM ELISA and the IgM-plus-IgG ELISA and the high correlation with the Serion classic ELISA indicate that they are useful in the diagnosis of LD.

ABSTRACTAn outbreak with a multiresistant Klebsiella pneumoniae(MRKP) strain among seven patients admitted to the adult intensive care unit (ICU) of a regional teaching hospital in The Netherlands was investigated. Epidemiologic investigations revealed a short delay between an operation and the acquisition of the MRKP strain. A case-control study comprising 7 cases and 14 controls was conducted to identify the risk factors associated with the acquisition of the MRKP strain. An operation at each of two operation rooms was strongly associated with the acquisition of the MRKP strain: odds ratio of 36 (95% confidence interval, 2.7 to 481.2; P= 0.003, Fisher exact two-tailed test). Cultures of environmental specimens of the operation rooms revealed contamination of the roll boards used to transport patients from the bed to the operation table with the MRKP strains. Molecular genotyping of the isolates revealed clonal similarity between the isolates of the seven cases, isolates from environmental specimen cultures, and in addition, an MRKP isolate from a repatriated ICU patient from earlier that year. The outbreak ended after cleaning and replacement of the roll boards in the operation rooms and implementation of additional barrier precautions for colonized or infected patients. It was concluded that two operation rooms played a significant role in the transmission of an MRKP strain between ICU patients during the presented outbreak.

The mecA gene was lost in 36 (14.4%) of 250 methicillin-resistant Staphylococcus aureus isolates after 2 years of storage at –80°C with the Microbank system (Pro-lab Diagnostics, Austin, Tex.). Further analysis of 35 of these isolates confirmed loss of the mecA gene in 32 isolates. This finding has important implications for the management of strain collections.

ABSTRACTThe mecAgene was lost in 36 (14.4%) of 250 methicillin-resistant Staphylococcus aureusisolates after 2 years of storage at -80°C with the Microbank system (Pro-lab Diagnostics, Austin, Tex.). Further analysis of 35 of these isolates confirmed loss of the mecAgene in 32 isolates. This finding has important implications for the management of strain collections.

ABSTRACTSeveral small clinical trials have indicated that antibiotic treatment of Chlamydia pneumoniaeinfection is associated with a better outcome in patients with coronary artery disease (CAD). It has not been demonstrated whether antibiotic treatment eradicates C. pneumoniaefrom vascular tissue. The aim of the present study was to assess the effect of clarithromycin on the presence of C. pneumoniaein the vascular tissue of patients with CAD. Patients who had CAD and who were waiting for coronary artery bypass graft surgery were enrolled in a randomized, double-blind, placebo-controlled trial. Patients were treated with clarithromycin at 500 mg or placebo once daily from the day of inclusion in the study until surgery. Several vascular tissue specimens were obtained during surgery. The presence of C. pneumoniaein vascular tissue specimens was examined by immunohistochemical staining (IHC) and two PCR assays. Chlamydiaimmunoglobulin G (IgG) titers were determined by an enzyme-linked immunosorbent assay at the time of inclusion in the study and 8 weeks after surgery. A total of 76 patients were included, and 180 vascular tissue specimens were obtained (80 specimens from the group treated with clarithromycin and 100 specimens from the group treated with placebo). Thirty-five patients received clarithromycin (mean duration, 27 days; standard deviation [SD], 12.2 days), and 41 patients received placebo (mean duration, 27 days; SD, 13.9 days). IHC detected the C. pneumoniaemajor outer membrane protein antigen in 73.8% of the specimens from the group treated with clarithromycin and 77.0% of the specimens from the group treated with placebo (Pwas not significant). Chlamydialipopolysaccharide antigen was found in only one specimen from the group that received placebo. C. pneumoniaeDNA was not detected in any specimen. Baseline Chlamydia-specific IgG titers were equally distributed in both groups and were not significantly different after treatment. There was no indication of an active C. pneumoniaeinfection in vascular tissue. Chlamydia-specific IgG titers remained unchanged throughout the study in both the antibiotic- and the placebo-treated patients.

ABSTRACTTo investigate the effect of slow-release (SR) clarithromycin on colonization and the development of resistance in oropharyngeal and nasal flora, a double-blind, randomized, placebo-controlled trial was performed with 8 weeks of follow-up. A total of 296 patients with documented coronary artery disease were randomized in the preoperative outpatient clinic to receive a daily dose of SR clarithromycin (500 mg) (CL group) or placebo tablets (PB group) until the day of surgery. Nose and throat swabs were taken before the start of therapy, directly after the end of therapy, and 8 weeks later. The presence of potential pathogenic bacteria was determined, and if they were isolated, MIC testing was performed. Quantitative culture on media with and without macrolides was performed for the indigenous oropharyngeal flora. In addition, analysis of the mechanism of resistance was performed with the macrolide-resistant indigenous flora. Basic patient characteristics were comparable in the two treatment groups. The average number of tablets taken was 15 (standard deviation = 6.4). From the throat swabs, Haemophilus parainfluenzaewas isolated and carriage was not affected in either of the treatment groups. Nasal carriage of Staphylococcus aureus, however, was significantly reduced in the CL group (from 35.3 to 4.3%) compared to the PB group (from 32.4 to 30.3%) (P< 0.0001; relative risk [RR], 7.0; 95% confidence interval [CI], 3.1 to 16.0). Resistance to clarithromycin was present significantly more frequently in H. parainfluenzaein the CL group after treatment (P= 0.007; RR, 1.6; 95% CI, 1.1 to 2.3); also, the percentage of patients with resistance to macrolides in the indigenous flora after treatment was significantly higher in the CL group (31 to 69%) (P< 0.0001; RR, 1.9; 95% CI, 1.4 to 2.5). This persisted for at least 8 weeks. This study shows that besides the effective elimination of nasal carriage of S. aureus, treatment with SR clarithromycin for approximately 2 weeks has a marked and sustained effect on the development of resistance in the oropharyngeal flora for at least 8 weeks.