Global prevalence of meticillin-resistant Staphylococcus aureus.
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Biomedical subjects
Publications and source records attributed to Henri A Verbrugh.
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The aim of this study was to determine whether polymorphisms of the glucocorticoid receptor gene, influencing glucocorticoid sensitivity, are associated with persistent nasal carriage of Staphylococcus aureus. Two nasal swab cultures were obtained from each of 2,929 participants. Subjects were classified as persistent carriers (n=563) if both cultures were positive. GG homozygotes of the exon 9beta polymorphism were associated with a 68% reduced risk of persistent S. aureus nasal carriage, whereas carriers of the codon 23 lysine allele displayed an 80% increased risk. Thus, genotype-dependent variation in the sensitivity to glucocorticoids is associated with tolerance toward staphylococcal nasal colonization.
OBJECTIVE: Nasal carriage of Staphylococcus aureus is an important risk factor for S. aureus infection and a reservoir for methicillin-resistant S. aureus. We investigated whether nose picking was among the determinants of S. aureus nasal carriage. SETTING AND PARTICIPANTS: The study cohort comprised 238 patients who visited the ear, nose, and throat (ENT) disease outpatient clinic of a tertiary care hospital and did not have a nose-specific complaint (defined as ENT patients) and 86 healthy hospital employees (including medical students and laboratory personnel). MEASUREMENTS: All participants completed a questionnaire on behavior regarding the nose and were screened for S. aureus nasal carriage; only ENT patients underwent nasal examination by an ear, nose, and throat physician for clinical signs of nose picking. RESULTS: Among ENT patients, nose pickers were significantly more likely than non-nose pickers to carry S. aureus (37 [53.6%] of 69 vs 60 [35.5%] of 169 patients; relative risk, 1.51 [95% confidence interval, 1.03-2.19]). Among healthy volunteers, there was a statistically significant positive correlation between the self-perceived frequency of nose picking and both the frequency of positive culture results (R=0.31; P=.004) and the load of S. aureus present in the nose (R=0.32; P=.003). CONCLUSION: Nose picking is associated with S. aureus nasal carriage. The role of nose picking in nasal carriage may well be causal in certain cases. Overcoming the habit of nose picking may aid S. aureus decolonization strategies.
BACKGROUND: Campylobacter jejuni is the predominant cause of antecedent infection in post-infectious neuropathies such as the Guillain-Barré (GBS) and Miller Fisher syndromes (MFS). GBS and MFS are probably induced by molecular mimicry between human gangliosides and bacterial lipo-oligosaccharides (LOS). This study describes a new C. jejuni-specific high-throughput AFLP (htAFLP) approach for detection and identification of DNA polymorphism, in general, and of putative GBS/MFS-markers, in particular. RESULTS: We compared 6 different isolates of the "genome strain" NCTC 11168 obtained from different laboratories. HtAFLP analysis generated approximately 3000 markers per stain, 19 of which were polymorphic. The DNA polymorphisms could not be confirmed by PCR-RFLP analysis, suggesting a baseline level of 0.6% AFLP artefacts. Comparison of NCTC 11168 with 4 GBS-associated strains revealed 23 potentially GBS-specific markers, 17 of which were identified by DNA sequencing. A collection of 27 GBS/MFS-associated and 17 enteritis control strains was analyzed with PCR-RFLP tests based on 11 of these markers. We identified 3 markers, located in the LOS biosynthesis genes cj1136, cj1138 and cj1139c, that were significantly associated with GBS (P = 0.024, P = 0.047 and P < 0.001, respectively). HtAFLP analysis of 13 highly clonal South African GBS/MFS-associated and enteritis control strains did not reveal GBS-specific markers. CONCLUSION: This study shows that bacterial GBS markers are limited in number and located in the LOS biosynthesis genes, which corroborates the current consensus that LOS mimicry may be the prime etiologic determinant of GBS. Furthermore, our results demonstrate that htAFLP, with its high reproducibility and resolution, is an effective technique for the detection and subsequent identification of putative bacterial disease markers.
Because little is known about the pathophysiology of invasive pulmonary aspergillosis (IPA), we examined changes in pulmonary and general physiology during this disease in an animal model. In a model of fatal left-sided IPA, 19 persistently neutropenic rats were monitored for clinical signs including body temperature, body weight and respiratory distress. A separate group of nine rats with IPA was used for measurements of arterial blood pressure, arterial O2 and CO2 pressure, lung compliance and surfactant function. Body temperature and body weight decreased, whereas respiratory distress increased during progression of the disease. Compared to uninfected controls, in rats with IPA arterial blood pressure and lung compliance were significantly lower, and left lung minimal surface tension was significantly higher. Right lung surfactant function was not affected. Arterial O2 and CO2 pressures were not different between rats with IPA and uninfected controls. Infection with Aspergillus fumigatus in neutropenic rats resulted in hypothermia, body weight loss and respiratory distress. Loss of left lung function was probably compensated by the uninfected right lung, even in a late stage of the disease. Circulatory failure was a major feature in the terminal phase of the infection.
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The epidemiology and risks of Staphylococcus aureus carriage in continuous peritoneal dialysis (CPD) patients was studied in a single tertiary-care institution. On outpatient visits samples for culture were routinely taken prospectively from the CPD catheter exit site and the vestibulum nasi. Seventy-five patients with at least one culture positive for S. aureus in this period were included: 43 had genotypically identical S. aureus strains in over 80% of the cultures and were classified as persistent carriers; 32 were intermittent carriers. Persistent carriage was associated with a threefold higher risk for CPD-related infections and sixfold higher rates of vancomycin consumption compared to those for the intermittent carriers. No methicillin or vancomycin resistance was detected.
A sudden increase in neutropenic hematology patients with Candida krusei colonization and bacteremia prompted a longitudinal epidemiological investigation. We identified 39 patients; 13 developed candidemia, and three died; 25 patients carried the same genotype. We intervened by changing antifungal prophylaxis and implementing strict infection control measures. The incidence dropped immediately.
The Staphylococcus aureus enterotoxin gene cluster, egc, was detected in isolates from healthy individuals and in those from patients with bacteremia. The egc genes cooccur and are slightly enriched in strains from healthy carriers (present in 63.7% of carriage-associated isolates versus 52.9% of invasive isolates; P = 0.03). Multilocus sequence typing revealed that successful staphylococcal clones usually harbor the egc locus.
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Campylobacter jejuni is the predominant cause of antecedent infection in Guillain-Barré syndrome (GBS) or Miller Fisher syndrome (MFS). C. jejuni probably triggers GBS or MFS through molecular mimicry between bacterial sialylated lipo-oligosaccharides (LOS) and gangliosides in peripheral nerve tissue. We investigated whether co-infections with multiple C. jejuni strains occur in GBS or MFS patients and we further characterized these strains. PFGE analysis of 83 C. jejuni isolates from single primary colonies from stool cultures of 13 patients with GBS or MFS revealed co-infection with two different strains in one patient (8%). We showed that only strain GB5.1 contained an LOS biosynthesis gene locus that is associated with neuropathy. The patient serum strongly reacted with the LOS of strain GB5.1 and not with the LOS of strain GB5.2. Mass spectrometry revealed that both strains expressed a non-sialylated outer core structure in their LOS. The patient serum contained anti-asialo-GM2 antibodies that cross-reacted with the LOS of strain GB5.1. This study demonstrates that co-infection with multiple C. jejuni strains occurs in GBS patients. Consequently, not all C. jejuni strains isolated from the faeces of a GBS patient are involved in the pathogenesis of GBS per se. Furthermore, this is the first report in which cross-reactivity of antibodies to asialo-GM2 and to the LOS of a C. jejuni strain from a GBS patient has been demonstrated. This finding suggests that molecular mimicry with non-sialylated structures may also be involved in the pathogenesis of GBS.
We screened 14,008 adult nonsurgical patients for Staphylococcus aureus nasal carriage at hospital admission and assessed them for invasive S. aureus disease and in-hospital mortality. Multilocus sequence typing was performed on endogenous invasive strains and nasal strains of matched asymptomatic carriers to investigate whether virulent clones could be identified in nasal carriers. Clonal complex (CC) 45 was significantly underrepresented (odds ratio [OR], 0.16 [95% confidence interval {CI}, 0.04-0.59]) and CC30 was overrepresented (not statistically significant) among invasive strains (OR, 1.91 [95% CI, 0.91-4.0]). The distribution of CCs of invasive S. aureus strains in noncarriers did not differ from that in carriers. Those infected with S. aureus strains belonging to a CC had higher mortality than those infected with strains not belonging to a CC (P<.05), which indicates the coevolution of S. aureus virulence and spread in humans.
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Staphylococcus aureus is a frequent cause of infections in both the community and hospital. Worldwide, the increasing resistance of this pathogen to various antibiotics complicates treatment of S aureus infections. Effective measures to prevent S aureus infections are therefore urgently needed. It has been shown that nasal carriers of S aureus have an increased risk of acquiring an infection with this pathogen. The nose is the main ecological niche where S aureus resides in human beings, but the determinants of the carrier state are incompletely understood. Eradication of S aureus from nasal carriers prevents infection in specific patient categories-eg, haemodialysis and general surgery patients. However, recent randomised clinical trials in orthopaedic and non-surgical patients failed to show the efficacy of eliminating S aureus from the nose to prevent subsequent infection. Thus we must elucidate the mechanisms behind S aureus nasal carriage and infection to be able to develop new preventive strategies. We present an overview of the current knowledge of the determinants (both human and bacterial) and risks of S aureus nasal carriage. Studies on the population dynamics of S aureus are also summarised.
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BACKGROUND: We investigated the impact of staphylococcal carriage among patients on continuous peritoneal dialysis (CPD) in a university hospital. METHODS: Patients were screened for Staphylococcus aureus carriage and categorized as persistent, intermittent, or non-S. aureus nasal carriers. Patients were subsequently recultured every 12 weeks for S. aureus and coagulase negative staphylococcal (CoNS) carriage, and followed-up for CPD-related infections and antibiotic resistance. RESULTS: Fifty-two patients were included: 20 peristent, 10 intermittent, and 22 non-S. aureus carriers. Only persistent S. aureus carriage was significantly associated with an increased risk for all CPD-related infections [incidence rate ratio (IRR) 3.52 (95% CI: 2.56-4.85)], exit site infections [IRR 5.59 (95% CI: 3.50-8.92)], and peritonitis [IRR 2.19 (95% CI: 1.39-3.45)], as well as increased antibiotic use [IRR 3.43 (95% CI: 2.50-4.72)], including vancomycin [IRR 2.15 (95%: 2.13-2.16)]. No vancomycin-resistant S. aureus strains were detected. However, eight (2%) out of 407 CoNS strains isolated were vancomycin intermediately susceptible. In all five patients (four persistent and one intermittent carriers) concerned, this was significantly related to a higher antibiotic (including vancomycin) usage [IRR 2.65 (95% CI: 1.82-3.84)]. CONCLUSION: Persistent-but not intermittent-S. aureus nasal carriage is the major determinant of CPD-related infections, and is associated with a significantly higher consumption of antibiotics, including vancomycin. The highly diverse population of CoNS appears to be the prime reservoir of staphylococcal vancomycin resistance. Accurate determination of the S. aureus nasal carriage state of CPD patients is essential to better target intervention strategies to prevent CPD-related infections.
Nasal carriage of Staphylococcus aureus is an important risk factor for S. aureus infections. Mupirocin nasal ointment is presently the treatment of choice for decolonizing the anterior nares. However, recent clinical trials show limited benefit from mupirocin prophylaxis in preventing nosocomial S. aureus infections, probably due to (re)colonization from extranasal carriage sites. Therefore, we studied the effectiveness of mupirocin nasal ointment treatment on the dynamics of S. aureus nasal and extranasal carriage. Twenty noncarriers, 26 intermittent carriers, and 16 persistent carriers had nasal, throat, and perineum samples taken 1 day before and 5 weeks after mupirocin treatment (twice daily for 5 days) and assessed for growth of S. aureus. The identities of cultured strains were assessed by restriction fragment length polymorphisms of the coagulase and protein A genes. The overall carriage rate (either nasal, pharyngeal, or perineal carrier or a combination) was significantly reduced after mupirocin treatment from 30 to 17 carriers (P = 0.003). Of the 17 carriers, 10 (60%) were still colonized with their old strain, 6 (35%) were colonized with an exogenous strain, and 1 (5%) was colonized with both. Two noncarriers became carriers after treatment. The acquisition of exogenous strains after mupirocin treatment is a common phenomenon. The finding warrants the use of mupirocin only in proven carriers for decolonization purposes. Mupirocin is effective overall in decolonizing nasal carriers but less effective in decolonizing extranasal sites.
A number of antimycobacterial agents were evaluated with respect to their bacteriostatic activity (growth inhibition) versus the bactericidal activity against a clinical isolate of Mycobacterium avium (Mycobacterium avium complex [MAC] strain 101) in relation to the time of exposure and the growth phase of the mycobacteria. In terms of growth inhibition the MAC in the active phase of growth was susceptible to clarithromycin, ethambutol, rifampin, amikacin, and the quinolones moxifloxacin, ciprofloxacin, and sparfloxacin. In terms of bactericidal activity in relation to the time of exposure these agents differed substantially with respect to the killing rate. An initial high killing capacity at low concentration was observed for amikacin, which in this respect was superior to the other agents. The bactericidal activity of clarithromycin and ethambutol was only seen at relatively high concentrations and increased with time. Killing by rifampin was concentration dependent as well as time dependent. The bactericidal activity of moxifloxacin was marginally dependent on the concentration or the time of exposure. The activity of clarithromycin in combination with ethambutol was not significantly enhanced compared to single-agent exposure. Only an additive effect was observed. The addition of rifampin or moxifloxacin as a third agent only marginally effected increased killing of MAC. However, by addition of amikacin the activity of the clarithromycin-ethambutol combination was significantly improved. The combination of amikacin and amoxicillin-clavulanic acid exhibited synergistic antimycobacterial activity. Towards MAC at low growth rates, only the quinolones exhibited a bactericidal effect.