Occult Nosocomial Infections

Even with a good surveillance program, nosocomial infections may be not recognized because of several reasons: absence of symptoms or prolonged incubation period (eg, viral bloodborne infections, tuberculosis); problems with the microbiological diagnosis, because adequate specimens may be difficult to obtain or special methods should be used (eg, fungal infections, virus, new agents); shorter hospital stays (eg, surgical-site infections); difficulty in distinguishing between nosocomial and community-acquired infections (eg, influenza); and failure to detect clinically relevant colonization (eg, multiresistant microorganisms). Because of the important potential consequences of occult nosocomial infections, specific surveillance programs should be designed to address these problem

Prophylaxis Failure Is Associated with a Specific Pneumocystis carinii Genotype

To investigate the possible association between Pneumocystis carinii types and various clinical and demographic parameters, we used molecular typing to analyze 93 bronchoalveolar lavage specimens from patients with P. carinii pneumonia (PCP). Multivariate regression analysis revealed an association between being infected with a specific P. carinii genotype and receiving anti-PCP prophylaxis (odds ratio, 4.4; 95% confidence interval, 1.0-18.6; P = .05), although no association with a specific drug was detecte

Molecular Epidemiology of Methicillin-Resistant Staphyloccocus aureus at a Low-Incidence Hospital over a 4-Year Period

Abstract Objective: To study the epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) over a prolonged period of time with the aid of a molecular typing method (ribotyping). Setting: A 1,000-bed tertiary university medical center. Patients and Methods: Defined epidemiological data were recorded for all patients culture-positive for MRSA between 1989 and 1992. Ribotyping of MRSA strains was performed using three restriction enzymes: EcoRv, HindHI, and KpnI. Results: From 1989 to 1992, MRSA was isolated from clinical specimens in 98 patients and from surveillance cultures in 27 patients. Among the 122 isolates available for typing, 26 different ribotypes were identified. In 20% of the cases, MRSA was community-acquired, and a third of these patients never had been hospitalized previously. Nine ribotypes were responsible for more than one case (2 to 64 patients); 17 appeared only once. Epidemiological data correlated with ribotyping results revealed 14 epidemiologic clusters involving six different ribotypes, whereas only three outbreaks were suspected initially. The median follow-up after the last isolation of a given ribotype was 14 months (range, 1 to 42) for clusters and 25 months (range, 1 to 46) for ribotypes that appeared only once. During clusters, only 16% of the cases occurred after the implementation of control measures in the ward (breakthrough cases). Conclusions: The high diversity of MRSA strains observed over 4 years suggested that new strains were introduced continuously in our hospital. Furthermore, that 17 ribotypes were isolated only once, that breakthrough cases represented only 16% of the cases in clusters, and that the follow-up duration after the last isolation of a given ribotype was more than 14 months suggest that infection control measures were effective in limiting the nosocomial spread of MRSA over a prolonged period of tim

The Impact of Penicillinase on Cefamandole Treatment and Prophylaxis of Experimental Endocarditis Due to Methicillin-Resistant Staphylococcus aureus

β-lactams active against methicillin-resistant Staphylococcus aureus (MRSA) must resist penicillinase hydrolysis and bind penicillin-binding protein 2A (PBP 2A). Cefamandole might share these properties. When tested against 2 isogenic pairs of MRSA that produced or did not produce penicillinase, MICs of cefamandole (8-32 mg/L) were not affected by penicillinase, and cefamandole had a ⩾40 times greater PBP 2A affinity than did methicillin. In rats, constant serum levels of 100 mg/L cefamandole successfully treated experimental endocarditis due to penicillinase-negative isolates but failed against penicillinase-producing organisms. This suggested that penicillinase produced in infected vegetations might hydrolyze the drug. Indeed, cefamandole was slowly degraded by penicillinase in vitro. Moreover, its efficacy was restored by combination with sulbactam in vivo. Cefamandole also uniformly prevented MRSA endocarditis in prophylaxis experiments, a setting in which bacteria were not yet clustered in the vegetations. Thus, while cefamandole treatment was limited by penicillinase, the drug was still successful for prophylaxis of experimental MRSA endocarditi

Interhuman Transmission as a Potential Key Parameter for Geographical Variation in the Prevalence of Pneumocystis jirovecii Dihydropteroate Synthase Mutations

Background. Pneumocystis jirovecii dihydropteroate synthase (DHPS) mutations are associated with failure of prophylaxis with sulfa drugs. This retrospective study sought to better understand the geographical variation in the prevalence of these mutations. Methods. DHPS polymorphisms in 394 clinical specimens from immunosuppressed patients who received a diagnosis of P. jirovecii pneumonia and who were hospitalized in 3 European cities were examined using polymerase chain reaction (PCR) single-strand conformation polymorphism. Demographic and clinical characteristics were obtained from patients' medical charts. Results. Of the 394 patients, 79 (20%) were infected with a P. jirovecii strain harboring one or both of the previously reported DHPS mutations. The prevalence of DHPS mutations was significantly higher in Lyon than in Switzerland (33.0% vs 7.5%; P<.001). The proportion of patients with no evidence of sulfa exposure who harbored a mutant P. jirovecii DHPS genotype was significantly higher in Lyon than in Switzerland (29.7% vs 3.0%; P<.001). During the study period in Lyon, in contrast to the Swiss hospitals, measures to prevent dissemination of P. jirovecii from patients with P. jirovecii pneumonia were generally not implemented, and most patients received suboptimal prophylaxis, the failure of which was strictly associated with mutated P. jirovecii. Thus, nosocomial interhuman transmission of mutated strains directly or indirectly from other individuals in whom selection of mutants occurred may explain the high proportion of mutations without sulfa exposure in Lyon. Conclusions. Interhuman transmission of P. jirovecii, rather than selection pressure by sulfa prophylaxis, may play a predominant role in the geographical variation in the prevalence in the P. jirovecii DHPS mutation

Importance of Genotypic and Phenotypic Tolerance in the Treatment of Experimental Endocarditis Due to Streptococcus gordonii

Genotypic and phenotypic tolerance was studied in penicillin treatment of experimental endocarditis due to nontolerant and tolerant Streptococcus gordonii and to their backcross transformants. The organisms were matched for in vitro and in vivo growth rates. Rats with aortic endocarditis were treated for 3 or 5 days, starting 12, 24, or 48 h after inoculation. When started at 12 h, during fast intravegetation growth, 3 days of treatment cured 80% of the nontolerant parent compared with <30% of the tolerant derivative (P < .005). When started at 24 or 48 h and if intravegetation growth had reached a plateau, 3 days of treatment failed against both bacteria. However, a significant difference between the 2 organisms was restored when treatment was extended to 5 days. Thus, genotypic tolerance conferred a survival advantage in both fast- and slow-growing bacteria, demonstrating that the in vitro-defined tolerant phenotype also carried the risk of treatment failure in viv

Quantitative Antibiogram as a Typing Method for the Prospective Epidemiological Surveillance and Control of MRSA Comparison with Molecular Typing

Abstract Objective: Evaluation of the quantitative antibiogram as an epidemiological tool for the prospective typing of methicillin-resistant Staphylococcus aureus (MRSA), and comparison with ribotyping. Methods: The method is based on the multivariate analysis of inhibition zone diameters of antibiotics in disk diffusion tests. Five antibiotics were used (erythromycin, clindamycin, cotrimoxazole, gentamicin, and ciprofloxacin). Ribotyping was performed using seven restriction enzymes (EcoRV, HindIII, KpnI, PstI, EcoRI, SfuI, and BamHI). Setting: 1,000-bed tertiary university medical center. Results: During a 1-year period, 31 patients were found to be infected or colonized with MRSA. Cluster analysis of antibiogram data showed nine distinct antibiotypes. Four antibiotypes were isolated from multiple patients (2, 4, 7, and 13, respectively). Five additional antibiotypes were isolated from the remaining five patients. When analyzed with respect to the epidemiological data, the method was found to be equivalent to ribotyping. Among 206 staff members who were screened, six were carriers of MRSA. Both typing methods identified concordant of MRSA types in staff members and in the patients under their care. Conclusions: The quantitative antibiogram was found to be equivalent to ribotyping as an epidemiological tool for typing of MRSA in our setting. Thus, this simple, rapid, and readily available method appears to be suitable for the prospective surveillance and control of MRSA for hospitals that do not have molecular typing facilities and in which MRSA isolates are not uniformly resistant or susceptible to the antibiotics teste

Association between a Specific Pneumocystis jiroveci Dihydropteroate Synthase Mutation and Failure of Pyrimethamine/Sulfadoxine Prophylaxis in Human Immunodeficiency Virus-Positive and -Negative Patients

To investigate the possible association between different prophylactic sulfa drugs and the genotype of the Pneumocystis jiroveci dihydropteroate synthase (DHPS) gene, we examined DHPS polymorphisms in clinical specimens from 158 immunosuppressed patients (38 HIV-negative and 120 HIV-positive), using polymerase chain reaction-single-strand conformation polymorphism. Fifty-seven (36.1%) of 158 patients were infected with a mutant DHPS genotype. All patients who developed P. jiroveci pneumonia (PcP) while receiving pyrimethamine/sulfadoxine (PM/SD) prophylaxis (n=14) had a strain harboring DHPS with an amino acid change at position 57 (Pro→Ser). This mutation was only present in 20 (14%) of 144 patients not receiving prophylaxis (P<.001). Hospitalization in a specific hospital was an independent risk factor for having P. jiroveci harboring the same DHPS mutation, which indirectly supports that interhuman transmission may affect the dissemination of the mutant strain