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Sterilization issues in vCJD: significance for prophylaxis
Letters to the Editor multiply antibiotic resistant Klebsiella pneumoniae controllable only by ward closure. J Hosp Infect 2001; 49: 183±192. 5. Martinez-Aguilar G, Alpuche-Aranda CM, Anaya C et al. Outbreak of nosocomial sepsis and pneumonia in a newborn intensive care unit by multiresistant extended-spectrum beta-lactamase-producing Klebsiella pneumoniae: high impact on mortality. Infect Control Hosp Epidemiol 2001; 22: 725±728. 6. Makhoul IR, Sujov P, Smolkin T et al. Epidemiological, clinical, and microbiological characteristics of late-onset sepsis among very low birth weight infants in Israel: a national survey. Pediatrics 2002; 109: 34±39.
doi:10.1053/jhin.2002.1333
Sterilization issues in vCJD: significance for prophylaxis Sir, The article on behalf of the variant Creutzfeld-Jacob disease (vCJD) Consensus Group1 illustrates one major factor: that it is currently impossible to carry out tests for sterility for vCJD; and hence the design or methods for achieving such sterility is problematic. As a result we are forced to use tests and methods known to be adequate for other transmissible spongiform encephalopathies (TSEs) in other animals. The agreement between the Central Sterilizing Club (CSC) and the Hospital Infection Society (HIS) shows acceptance that specific methods that are assumed to be adequate in scrapie and other TSEs are also expected to be effective in vCJD. This is reasonable as prion disease strains seem to be affected similarly by specific environmental factors. It is also logical from what we know of the mode of multiplication of the agent, and the way in which infectivity remains despite specific sterilizing procedures. However it does raise some quite important issues: (1) Repeatedly throughout the bovine spongiform encephalopathy (BSE) epidemic officials and advice groups had claimed that it would not spread to other species in a manner similar to other TSE strains. The Phillips' Inquiry3 showed that this was a mistake and that humans were being, and had been, put at risk. Phillips made it clear that waiting for proof that the horse has bolted before shutting the door was not wise in a disease
155
such as this. Action had to be taken in advance of proof of major human risk. (2) Pentosan polysulphate acts at low toxicity concentrations as a prophylactic agent against scrapie in mice and hamsters.2 The mode of action is by the drug attaching to a heparin-binding site on the surface of the prion. However the Medicines Control Agency (MCA) decided that it should not be expected to act against vCJD prions in humans and that a drug should only be licensed as a prophylactic if proof was available. The logic of the CSC and HIS agrees with that of several experts in the field: that the MCA standard thinking is unwise in this specific aspect, and that this drug should be made available for prescription to specific, named patients considered to be put at recent risk of vCJD (e.g., having received the blood of an infected person). (3) The article1 described the position in September 2000 and literature in this field is progressing rapidly. As a result, perhaps, it has not taken into account the specific decisions by foreign agencies e.g. by the WHO, the USA (concerning blood transfusion risks), and the EC, all of which are of significance. Spencer and Ridgeway have reported what is a reasonable line of thinking, and I feel that this should be followed up with recommendations about prophylaxis. As such, this drug, which acts in a known way against prions in animals should be assumed to work similarly in humans against vCJD until there is some evidence that it does not. The MCA has never had to follow such a consideration before, but the potential nosocomial risks of vCJD may mean that we should follow the CSC and HIS logic and have the drug available. Phillips' clear decision3 that official groups should act against human risk even before proof was present may suggest that MCA logic should be questioned. S. Dealler
Burnley General Hospital, Burnley, UK
References 1. Spencer RC, Ridgway GL. Sterilization issues in vCJDtowards a consensus. J Hosp Infect 2002; 51: 168±174. 2. Dealler SF. Transmissible spongiform encephalopathies: current and future therapeutic strategies. Rev Med Micro 1998; 9: 135±151.
156
Letters to the Editor
3. Lord Phillips of Worth Matravers, Bridgeman J, Ferguson-Smith, M. The BSE Inquiry: The Report. Volume 1: Findings and Conclusions Section 14. Lessons to be learned. 2000; HMSO, London.
doi:10.1053/jhin.2002.1346
Spread of a dominant methicillin-resistant Staphylococcus aureus (MRSA) clone between Uruguayan and South of Brazil Hospitals
Sir, Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most important causes of hospitalacquired infection. Epidemiological studies of infections caused by MRSA have shown the presence of a dominant clone in most populations analysed.1±3 One of these, the Iberian clone, seems to be widely spread in some European countries.1±3 Another epidemic MRSA clone, was found in six major Brazilian hospitals, located apart from each other,4 and spread with facility. This clone was identified in Portuguese hospitals,5 indicating intercontinental spread. We examined the distribution of MRSA strains in Porto Alegre (South of Brazil) and Montevideo (Uruguay) hospitals. Two hundred and eighty MRSA strains were isolated between 1996 and 1998 from patients in four hospitals in Porto Alegre; Brazil (7), and five hospitals in Montevideo Uruguay. Two French epidemic MRSA strains6 were provided by the Service de
Microbiologie MeÂdicale, Institut Gustave Roussy, France, for comparisons. The mecA gene was identified as decribed by Vannuffel et al.7 Ten mecA negative strains were eliminated from this study. Pulsed-field gel electrophoresis (PFGE) was performed on bacterial DNA digested with SmaI enzyme (Gibco BRL) and performed in a CHEF-DR II (BioRad). Interpretation of PFGE patterns was by the Molecular Analyst Fingerprinting software (BioRad). Strains were classified according to the criteria proposed for the interpretation of restriction patterns produced by PFGE.8 The SmaI restriction patterns obtained for the 270 MRSA strains were classified in 20 distinct PFGE patterns (A to T). The pattern A, containing 130 strains (48%), is present in all Porto Alegre hospitals and four Montevideo hospitals. The pattern G, with 22 strains (8.2%), were found only in Porto Alegre. Pattern M (22 strains) and the pattern P (seven strains) were exclusively from Uruguayan hospitals. The epidemic French MRSA analysed showed 74% similarity with pattern A. An example of major PFGE patterns is shown in Figure 1(a). DNA present in the PFGE gels was transferred to nylon membranes for Southern blotting analysis. The chromosomal location of the mecA gene was investigated in samples from major PFGE patterns using an internal probe of the mecA gene [Figure 1(b)]. Pattern A showed the mecA gene located on a 125 kb fragment. Pattern M, from Uruguayan hospitals, and the two epidemic French MRSA strains had the mecA gene in a 200 kb fragment. Pattern G [Figure 1(a), lane 18], inspite of a band next to 200 kb, showed a mecA fragment in a 140 kb fragment [Figure 1(b), lane 18].
Figure 1 (a) Major PFGE patterns of MRSA clinical isolates. The PFGE gel (a) was also tested with a mecA DNA probe (b). Lanes 1 and 21, molecular marker (lambda oligomers). Lanes 2 and 3: pattern A7; lanes 4 to 7: pattern P1; lanes 8 to 12: pattern A1; lanes 13 to 17: pattern M; lane 18: pattern G. Lanes 19 and 20: French epidemic MRSA strains. Arrows and numbers at right (b) show molecular size in kilobases.
doi:10.1053/jhin.2002.1333
Sterilization issues in vCJD: significance for prophylaxis Sir, The article on behalf of the variant Creutzfeld-Jacob disease (vCJD) Consensus Group1 illustrates one major factor: that it is currently impossible to carry out tests for sterility for vCJD; and hence the design or methods for achieving such sterility is problematic. As a result we are forced to use tests and methods known to be adequate for other transmissible spongiform encephalopathies (TSEs) in other animals. The agreement between the Central Sterilizing Club (CSC) and the Hospital Infection Society (HIS) shows acceptance that specific methods that are assumed to be adequate in scrapie and other TSEs are also expected to be effective in vCJD. This is reasonable as prion disease strains seem to be affected similarly by specific environmental factors. It is also logical from what we know of the mode of multiplication of the agent, and the way in which infectivity remains despite specific sterilizing procedures. However it does raise some quite important issues: (1) Repeatedly throughout the bovine spongiform encephalopathy (BSE) epidemic officials and advice groups had claimed that it would not spread to other species in a manner similar to other TSE strains. The Phillips' Inquiry3 showed that this was a mistake and that humans were being, and had been, put at risk. Phillips made it clear that waiting for proof that the horse has bolted before shutting the door was not wise in a disease
155
such as this. Action had to be taken in advance of proof of major human risk. (2) Pentosan polysulphate acts at low toxicity concentrations as a prophylactic agent against scrapie in mice and hamsters.2 The mode of action is by the drug attaching to a heparin-binding site on the surface of the prion. However the Medicines Control Agency (MCA) decided that it should not be expected to act against vCJD prions in humans and that a drug should only be licensed as a prophylactic if proof was available. The logic of the CSC and HIS agrees with that of several experts in the field: that the MCA standard thinking is unwise in this specific aspect, and that this drug should be made available for prescription to specific, named patients considered to be put at recent risk of vCJD (e.g., having received the blood of an infected person). (3) The article1 described the position in September 2000 and literature in this field is progressing rapidly. As a result, perhaps, it has not taken into account the specific decisions by foreign agencies e.g. by the WHO, the USA (concerning blood transfusion risks), and the EC, all of which are of significance. Spencer and Ridgeway have reported what is a reasonable line of thinking, and I feel that this should be followed up with recommendations about prophylaxis. As such, this drug, which acts in a known way against prions in animals should be assumed to work similarly in humans against vCJD until there is some evidence that it does not. The MCA has never had to follow such a consideration before, but the potential nosocomial risks of vCJD may mean that we should follow the CSC and HIS logic and have the drug available. Phillips' clear decision3 that official groups should act against human risk even before proof was present may suggest that MCA logic should be questioned. S. Dealler
Burnley General Hospital, Burnley, UK
References 1. Spencer RC, Ridgway GL. Sterilization issues in vCJDtowards a consensus. J Hosp Infect 2002; 51: 168±174. 2. Dealler SF. Transmissible spongiform encephalopathies: current and future therapeutic strategies. Rev Med Micro 1998; 9: 135±151.
156
Letters to the Editor
3. Lord Phillips of Worth Matravers, Bridgeman J, Ferguson-Smith, M. The BSE Inquiry: The Report. Volume 1: Findings and Conclusions Section 14. Lessons to be learned. 2000; HMSO, London.
doi:10.1053/jhin.2002.1346
Spread of a dominant methicillin-resistant Staphylococcus aureus (MRSA) clone between Uruguayan and South of Brazil Hospitals
Sir, Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most important causes of hospitalacquired infection. Epidemiological studies of infections caused by MRSA have shown the presence of a dominant clone in most populations analysed.1±3 One of these, the Iberian clone, seems to be widely spread in some European countries.1±3 Another epidemic MRSA clone, was found in six major Brazilian hospitals, located apart from each other,4 and spread with facility. This clone was identified in Portuguese hospitals,5 indicating intercontinental spread. We examined the distribution of MRSA strains in Porto Alegre (South of Brazil) and Montevideo (Uruguay) hospitals. Two hundred and eighty MRSA strains were isolated between 1996 and 1998 from patients in four hospitals in Porto Alegre; Brazil (7), and five hospitals in Montevideo Uruguay. Two French epidemic MRSA strains6 were provided by the Service de
Microbiologie MeÂdicale, Institut Gustave Roussy, France, for comparisons. The mecA gene was identified as decribed by Vannuffel et al.7 Ten mecA negative strains were eliminated from this study. Pulsed-field gel electrophoresis (PFGE) was performed on bacterial DNA digested with SmaI enzyme (Gibco BRL) and performed in a CHEF-DR II (BioRad). Interpretation of PFGE patterns was by the Molecular Analyst Fingerprinting software (BioRad). Strains were classified according to the criteria proposed for the interpretation of restriction patterns produced by PFGE.8 The SmaI restriction patterns obtained for the 270 MRSA strains were classified in 20 distinct PFGE patterns (A to T). The pattern A, containing 130 strains (48%), is present in all Porto Alegre hospitals and four Montevideo hospitals. The pattern G, with 22 strains (8.2%), were found only in Porto Alegre. Pattern M (22 strains) and the pattern P (seven strains) were exclusively from Uruguayan hospitals. The epidemic French MRSA analysed showed 74% similarity with pattern A. An example of major PFGE patterns is shown in Figure 1(a). DNA present in the PFGE gels was transferred to nylon membranes for Southern blotting analysis. The chromosomal location of the mecA gene was investigated in samples from major PFGE patterns using an internal probe of the mecA gene [Figure 1(b)]. Pattern A showed the mecA gene located on a 125 kb fragment. Pattern M, from Uruguayan hospitals, and the two epidemic French MRSA strains had the mecA gene in a 200 kb fragment. Pattern G [Figure 1(a), lane 18], inspite of a band next to 200 kb, showed a mecA fragment in a 140 kb fragment [Figure 1(b), lane 18].
Figure 1 (a) Major PFGE patterns of MRSA clinical isolates. The PFGE gel (a) was also tested with a mecA DNA probe (b). Lanes 1 and 21, molecular marker (lambda oligomers). Lanes 2 and 3: pattern A7; lanes 4 to 7: pattern P1; lanes 8 to 12: pattern A1; lanes 13 to 17: pattern M; lane 18: pattern G. Lanes 19 and 20: French epidemic MRSA strains. Arrows and numbers at right (b) show molecular size in kilobases.