Nasal decolonization of Staphylococcus aureus with mupirocin: strengths, weaknesses and future prospects.

Staphylococcus aureus in the nose is a risk factor for endogenous staphylococcal infection. UK guidelines recommend the use of mupirocin for nasal decolonization in certain groups of patients colonized with methicillin-resistant S. aureus (MRSA). Mupirocin is effective at removing S. aureus from the nose over a few weeks, but relapses are common within several months. There are only a few prospective randomized clinical trials that have been completed with sufficient patients, but those that have been reported suggest that clearance of S. aureus from the nose is beneficial in some patient groups for the reduction in the incidence of nosocomial infections. There is no convincing evidence that mupirocin treatment reduces the incidence of surgical site infection. New antibiotics are needed to decolonize the nose because bacterial resistance to mupirocin is rising, and so it will become less effective. Furthermore, a more bactericidal antibiotic than mupirocin is needed, on the grounds that it might reduce the relapse rate, and so clear the patient of MRSA for a longer period of time than mupirocin.

Congenital cataract, muscular hypotonia, developmental delay and sensorineural hearing loss associated with a defect in copper metabolism.

Deficiencies of different proteins involved in copper metabolism have been reported to cause human diseases. Well-known syndromes, for example, are Menkes and Wilson diseases. Here we report a patient presenting with congenital cataract, severe muscular hypotonia, developmental delay, sensorineural hearing loss and cytochrome-c oxidase deficiency with repeatedly low copper and ceruloplasmin levels. These findings were suggestive of a copper metabolism disorder. In support of this, the patient's fibroblasts showed an increased copper uptake with normal retention. Detailed follow-up examinations were performed. Immunoblotting for several proteins including ATP7A (MNK or Menkes protein), ATP7B (Wilson protein) and SOD1 showed normal results, implying a copper metabolism defect other than Wilson or Menkes disease. Sequence analysis of ATOX1 and genes coding for proteins that are known to play a role in the mitochondrial copper metabolism (COI-III, SCO1, SCO2, COX11, COX17, COX19) revealed no mutations. Additional disease genes that have been associated with cytochrome-c oxidase deficiency were negative for mutations as well. As beneficial effects of copper histidinate supplementation have been reported in selected disorders of copper metabolism presenting with low serum copper and ceruloplasmin levels, we initiated a copper histidinate supplementation. Remarkable improvement of clinical symptoms was observed, with complete restoration of cytochrome-c oxidase activity in skeletal muscle.

Microbicides--evaluating multiple formulations of C31G.

Despite a significant worldwide need for effective microbicides to reduce sexually transmitted diseases (STD) and HIV transmission, none is currently available. C31G, a surface active anti-infective agent that is active in vitro against bacterial and viral STD pathogens, was evaluated in a 3-day, once-daily dosing clinical trial designed to assess multiple formulations for safety and acceptance. The trial used a scoring algorithm that was based on relevant subject reported symptoms and signs observed at follow-up. Differences in tolerance and acceptability between the formulations were demonstrated, as was consistency with the results from a previous 7-day trial that involved two of the formulations (1.2% HEC gel, 2.0% N-9). The 1.0% C31G co-polymer gel was the best tolerated, most acceptable formulation, and will be advanced to longer, more comprehensive trials. Thus, formulation differences are relevant to microbicide tolerance and acceptability, and the 3-day trial design validated in this study can be used to assess formulations.

Surveillance of antimicrobial resistance--what, how and whither?

OBJECTIVE: To express the views of a working party held to consider antibiotic resistance surveillance systems, their strengths and weaknesses, and their current and future applications. METHODS: The participants, all of whom were experienced in this field, discussed the development of surveillance systems in relation to the increasing prevalence of resistance to antibacterial agents and the current interest in surveillance systems shown by many official bodies, in both the human and veterinary fields. The problems inherent in surveillance systems were considered together with the applications of different systems. RESULTS: The properties of good antibiotic resistance surveillance systems were defined. Surveillance systems vary widely from those with a narrow base, focusing on few organisms in one disease area, to those covering many diseases, many organisms (including normal flora) and many compounds. Whatever their design, they should be able to detect significant differences and shifts in susceptibility to various antibacterial agents, and the information derived from them should reach as many interested parties as possible in a timely manner. In using this information to decide strategies, criteria for action need to be determined by pragmatic consensus. Funding remains a major problem, with few large studies being supported by official bodies in spite of their professed enthusiasm for surveillance. In consequence, many current systems are funded by the pharmaceutical industry and are of necessity restricted in their focus. CONCLUSIONS: Antibiotic resistance surveillance studies should and can be well planned and well executed. Many current systems suffer from well-recognized but uncorrected biases. Consortium funding will be necessary for large schemes to be successful. There is no "ideal" surveillance system.

The millennium bugs--the need for and development of new antibacterials.

Global antibacterial resistance is becoming an increasing public health problem. Bacteria resistant to almost all of the available antibacterials have been identified. The pharmaceutical industry and fledgling biotechnology companies are responding to the threat of antibiotic resistance with renewed efforts to discover novel antibacterials in attempts to overcome bacterial resistance. Both short term and long term strategies are being vigorously pursued. Short-term efforts are focused on developing novel antibacterial agents with a narrow spectrum of action to combat the problem of gram-positive resistant bacteria. Long-term approaches include the use of microbial genomic sequencing techniques to discover novel agents active against potentially new bacterial targets. Better use of existing agents using pharmacodynamic data to optimise antibiotic regimens is increasingly being addressed and the hope is that such measures will prevail until the newer agents are available.

Self-medication of antibacterials without prescription (also called 'over-the-counter' use). A report of a Working Party of the British Society for Antimicrobial Chemotherapy.

The availability of antimicrobial agents for self-medication may increase and could include antibacterial agents for oral or topical use. Wholesale deregulation of antibacterials would be undesirable and likely to encourage misuse of classes of agents currently important in the management of serious infections. Changed regulation from Prescription-Only Medicine (POM) to Pharmacy (P) medicine of selected agents with indications for short-term use in specific minor infections and illness is likely to have advantages to the user. However, safeguards to their use would need to be included in the Patient Information Leaflet (PIL). Agents and indications for self-medication are discussed. Any alteration in licensed status from POM to P will require careful risk-benefit assessment, including the likely impact on bacterial resistance. Safety issues also include concerns relating to age of the user, pregnancy, underlying disease and the potential for drug interactions. The importance of appropriate information with the PIL is emphasized, as is the role of the pharmacist, while ways of improving adverse event notification and monitoring are discussed. The paucity of good denominator-controlled data on the prevalence of in-vitro resistance is highlighted, and recommendations for improving the situation are made. There are currently no levels of resistance accepted by regulatory bodies on which to base a licensing decision, be it for granting a product licence, renewal of a licence or a change in licensed status from POM to P. Due consideration should be given to: the validation of user-defined indications in comparison with those medically defined; the enhancement of pharmacy advice in the purchase of such agents; improved safety monitoring; the establishment of systematic surveillance of susceptibility data.

Cerebral manifestation of Wilson's disease successfully treated with liver transplantation.

The main indication for orthotopic liver transplantation (OLTx) in Wilson's disease (WD) is severe hepatic decompensation. Our 15-year-old patient is the second case to date in whom OLTx was performed because of neurologic manifestations resulting from WD. His initial condition involving recurrent headaches, tremor, and athetoid hand movements progressively deteriorated during therapy with D-penicillamine, zinc sulfate, and trientine until he was severely dysarthric, unable to walk, and bedridden. After OLTx, his neurologic condition became almost normal.

Molecular approaches to diagnosis of pulmonary diseases due to Mycoplasma pneumoniae.

In this prospective study, the use of a culture-enhanced PCR assay for the detection of Mycoplasma pneumoniae, followed by hybridization with a specific probe (MP-HPCR) or without hybridization (MP-PCR), and the use of a nested PCR (MP-NPCR) were evaluated. Clinical samples (190 specimens) from 190 patients with respiratory complaints were incubated in culture broth overnight and then subjected to PCR. The results of the PCR were compared to those obtained by culture, the direct antigen test, and serologic testing by microparticle agglutination and by immunoblotting in unclear cases. The sensitivities were 19 CFU for MP-PCR, 1.9 CFU for MP-HPCR, and 0.019 CFU for MP-NPCR. PCR amplification of the beta-globin gene was possible in 98% of cases: after dilution of the beta-globin-negative samples, all samples were reactive. Correlation between negative MP-NPCR results and negative serology results was found in 89% of cases; a positive correlation was found with 10% of the patients. Samples from three immunocompromised patients were MP-NPCR positive but serologically negative. High respiratory colonization by M. pneumoniae (>10(5) CFU/ml) in patients with acute respiratory disease could be detected by culture, MP-PCR, and MP-NPCR. These results indicate that MP-PCR and MP-NPCR are reliable methods for the detection of M. pneumoniae in respiratory tract samples of patients with respiratory complaints.

Molecular discrimination between Campylobacter jejuni, Campylobacter coli, Campylobacter lari and Campylobacter upsaliensis by polymerase chain reaction based on a novel putative GTPase gene.

Polymerase chain reaction (PCR) mediated DNA fingerprinting has resulted in the identification of a novel Campylobacter jejuni gene, encoding a GTPase protein. The gene, consisting of 383 amino acids contained semi-conserved GTP-binding sites (designated G-1 to G-4), that are characteristic for members of the GTPase protein superfamily. Remarkably, this gene from C. Jejuni appears to encode a member of a novel family of GTP-binding proteins, containing two separate putative GTP-binding domains, each comprising a series of semi-conserved GTP-binding motifs. Spacing between these motifs is highly conserved. Based on this novel gene, a general PCR strategy for the identification of C. jejuni, C. coli, C. lari and C. upsaliensis was developed. PCR primers were deduced from GTP-binding motifs G-1 and G-3 of the first GTP-binding domain. These GTP-binding sites flank a variable region of precisely 117 bp in the four Campylobacter spp. that allowed the development of species-specific probes. This PCR-hybridization assay offers a novel tool for rapid molecular detection and specific identification of the thermophilic Campylobacter spp.

Antibiotic resistance: a view from the pharmaceutical industry.

The development of new antibiotics has been successful in significantly reducing morbidity and mortality. With increasing use there has occurred an increase in antibiotic resistance but not a parallel increase in new agents with significantly improved spectrum of activity. Without concerted action from the pharmaceutical industry, physicians, academia, health care providers, and governments, the prospects look gloomy.

[Periodic breathing with periodic oxygen variation in infancy]. / Periodische Atmung mit periodischen Sauerstoffschwankungen im Säuglingsalter.

Oxycardiorespirographies, recording arterial oxygen saturation (SaO2), breathing movements, heart rate and ECG with a mean recording time of 22.3 hours, were performed on 85 preterm (mean postconceptional age: 38 weeks) and 81 term infants (mean postconceptional age 42.4 weeks). 83% of the preterm infants showed periodic breathing (PB), in 97% of them this was accompanied by periodic variations of arterial oxygen saturation (PVO). Periodic breathing occurred in 61% of the term infants, 84% of them showed PVO during periodic breathing. The mean variation of oxygen saturation was between 92.8 and 96.8% (+/- 1.7) for preterm and between 92.9 and 96.0% (+/- 2.2) for term infants. In some infants the peak to peak amplitude of the SaO2 cycles was up to 22%, sometimes a further fall of SaO2 occurred. There was a strong correlation of the PVO both at the beginning and end of the episode as well as with the PB-cycle periodicity itself. The fall of the oxygen saturation occurred 3.1 to 7.8 s after the beginning of the first apnea of an episode of periodic breathing, the minimum SaO2 was reached approximately 4.2 to 8.6 s later. This periodic rapid fall of SaO2 from a high oxygenation level cannot be explained by the apneas of a rather short duration during periodic breathing. It is discussed that PVO during periodic breathing may be caused by an ideopathic right to left shunting across fetal circulation pathways which occurs intermittently and periodically. This mechanism could-via patterns of reaction exhibited during the fetal and neonatal time period-lead to acute hypoxemia, as found in apparently life threatening events (ALTE) and as postulated in sudden infant death (SID).

Multicenter evaluation of arbitrarily primed PCR for typing of Staphylococcus aureus strains.

Fifty-nine isolates of Staphylococcus aureus and a single strain of Staphylococcus intermedius were typed by arbitrarily primed PCR (AP-PCR). To study reproducibility and discriminatory abilities, AP-PCR was carried out in seven laboratories with a standardized amplification protocol, template DNA isolated in a single institution, and a common set of three primers with different resolving powers. The 60 strains could be divided into 16 to 30 different genetic types, depending on the laboratory. This difference in resolution was due to differences in technical procedures (as shown by the deliberate introduction of experimental variables) and/or the interpretation of the DNA fingerprints. However, this did not hamper the epidemiologically correct clustering of related strains. The average number of different genotypes identified exceeded those of the more traditional typing strategies (F. C. Tenover, R. Arbeit, G. Archer, J. Biddle, S. Byrne, R. Goering, G. Hancock, G. A. Hebert, B. Hill, R. Hollis, W. R. Jarvis, B. Kreiswirth, W. Eisner, J. Maslow, L. K. McDougal, J. M. Miller, M. Mulligan, and M. A. Pfaller, J. Clin. Microbiol. 32:407-415, 1994). Comparison of AP-PCR with pulsed-field gel electrophoresis (PFGE) indicated the existence of strains with constant PFGE types but variable AP-PCR types. The reverse (constant AP-PCR and variable PFGE patterns) was also observed. This indicates additional resolution for combined analyses. It is concluded that AP-PCR is well suited for genetic analysis and monitoring of nosocomial spreading of staphylococci. The interlaboratory reproducibility of DNA-banding patterns and the intralaboratory standardization need improvement.

Comparison of four genotyping assays for epidemiological study of methicillin-resistant Staphylococcus aureus.

Twenty-six methicillin-resistant Staphylococcus aureus strains were genetically differentiated by interrepeat PCR and the results compared with those of ribotyping, pulsed-field gel electrophoresis (PFGE) and random amplified polymorphic DNA analysis obtained in a previous study for the same strains. The comparison showed that the PCR-mediated assays were as discriminatory as PFGE, whereas ribotyping was the least powerful genotyping method. Due to the ease of performance, PCR fingerprinting may become the method of choice for establishing clonal relationship among Staphylococcus aureus isolates.