Frecuencia de Aparición de Estafilococos Resistentes a Meticilina, Conclusiones

1. Nuestros resultados reflejan la prevalencia de 27% de cepas de Staphylococcus sp. resistentes a meticilina, para las cuales predomina en 77%, el fenotipo de resistencia heterogéneo con la presencia del gen mecA, mientras que 23% posee otros mecanismos de resistencia que necesitan ser detectados por la determinación de la concentración mínima inhibitoria (MIC).

2. Se demostró la existencia en estas cepas de resistencia cruzada a otras familias de antibióticos, así como la presencia en todas de penicinilasas.

3. Del total de cepas ensayadas, 93% es resistente a penicilinas y 17 % presenta un fenotipo inducible de resistencia a antibióticos macrólidos.

4. Los resultados de resistencia encontrados son el reflejo de las ventajas obtenidas de la aplicación de una política de uso racional de antibióticos, lo que implica un control directo sobre la resistencia, una protección a los antibióticos como recursos naturales y por consiguiente una mejora en la calidad de vida del paciente. Sin embargo, debemos mantener una vigilancia sistemática en nuestros hospitales para prevenir un aumento de resistencia y la aparición de brotes fatales.

5. Aunque la investigación de los mecanismos moleculares de la resistencia a la meticilina ha avanzado, aún no hemos llegado al nivel de conocimiento necesario para controlar este fenómeno. Se espera que la total comprensión de los mecanismos de resistencia del MRSA se logre tomando en consideración la diversidad genética de la especie S. aureus. Desde este punto de vista, los estudios futuros deben incluir la identificación epidemiológica de esas cepas que son analizadas.

6. La vigilancia a nivel mundial de la resistencia a los antibióticos ayudará a identificar los factores que llevan a la emergencia y a la diseminación de dichos aislados y por tanto, permitirá descubrir nuevos genes o factores que conducirán a la mejor comprensión de este fenómeno y su control.

Summary

In this study we evaluated 425 nosocomial strains of Staphylococcus sp. which were obtained from seven hospitals in Habana (Cuba), following the reference methods suggested in the guidelines of NCCLS. The mechanism of resistance in all resistant strains was determined and also the presence of the mecA gen, using the polymerase chain reaction (PCR). A correlation was established between the mechanism of resistance, disc diffusion methods and MIC’s. Of all 425 strains, 273 (68%) were S. aureus and133 (32%) Staphylococcus coagulase negative. In general, 27% of all strains were methicillin-resistant by the disc-diffusion method, 25% grew in the presence of oxacillin and only 21% were carriers of the mecA gen. 22% of the S. aureus isolates were resistant to oxacillin by the disc-diffusion method, whereas 20% grew in the Müller-Hinton-oxacillin plates and demonstrated the presence of the mecA gen, showing that 98% of methicillin resistance was due to production of PBP2A. In the case of coagulase-negative Staphylococcus, only 24% of the oxacillin-resistant isolates were conditioned by the presence of mecA; other mechanisms, mainly beta-lactamase production, was involved in the rest of the strains.

All methicillin-resistant strains were resistant to penicillins and also showed high degree of cross resistance with erithromycin (60-68%), trimethoprim-sulfa (72-84%), tetracycline (55-50%), cloramphenicol (53-51%) and gentamicin (48-50%) for S. aureus and coagulase negative Staphylococcus respectively.

These results establish for the first time information about the current state of resistance among Staphylococcus sp. in Habana. It also alerts the Minister of Public Health about the potential of rapid dissemination of these strains to other areas of the city and their ability for developing vancomycin intermediate or resistant strains.

Referencias

1. Noble WC. Antibiotic resistance in the staphylococci. Science progress 1997;80: 5.
2. Brakstad OG, Maeland J. Mechanisms of methicillin resistance in staphylococci. APMIS 1997;105: 264.
3. Paulsen IT, Firth N, Skurray RA. Resistance to antimicrobial agents other than ß-lactams. In: Archer GL, Crossley K, eds. The staphylococci in human disease. New York: Churchill Livingstone; 1996: 175-212.
4. Machida K. MRSA. Rinsho Byori. Japanese Journal of Clinical Pathology 1999;47: 533.
5. Angeles Dominguez M, et al. Spread and Maint e n a n c e o f a D omi n a n t Me t h i c i l l i n-R e s i s t a n t Staphylococcus aureus (MRSA) Clone during an outbreak of MRSA Disease in a Spanish Hospital. Journal of Clinical Microbiology 1994;32: 2081.
6. Coello R, et al. Prospective Study of Infection, Colonization and Carriage of Methicillin-Resistant Staphylococcus aureus in an Outbreak affecting 990 patients. European Journal of Clinical Microbiology and Infectious Diseases 1994;13: 74.
7. Struelens MJ, Mertens R and the Groupement pour le Dépistage, l’Etude et la Prévention des Infections Hospitalières. National Survey of Methicillin-Resistant Staphylococcus aureus in Belgian Hospitals: Detection Methods, Prevalence Trends and Infection Control Measures European Journal of Clinical Microbiology and Infectious Diseases 1994;13: 56.
8. Schmitz FJ, Geisel R, Wagner S, Lenz W, Kamla V, Heinz HP, Idel H, Hadding U. Typing, resistance behavior and occurrence of methicillin-resistant Staphylococcus aureus strains in a surgical intensive care unit. Zentralblatt fur Hygiene und Umweltmedizin 1996;198: 355.
9. Durmaz B, Durmaz R, Sahin K. Methicillin-resistance among Turkish isolates of Staphylococcus aureus strains from nosocomial and community infections and their resistance patterns using various antimicrobial agents. Journal of Hospital Infection 1997;37:325.
10. De Neeling AJ, Van Leeuwen WJ, Schouls LM, et al. Resistance of staphylococci in The Netherlands: surveillance by an electronic network during 1989-1995. Journal of Antimicrobial Chemotherapy 1998;41: 93.
11. Suh K, Toye B, Jessamine P, Chan F, Ramotar K. Epidemiology of methicillin-resistant Staphylococcus aureus in three Canadian tertiary-care centers. Infection Control and Hospital Epidemiology 1998;19: 395.
12. O’Kane GM, Gottlieb T, Bradbury R. Staphylococcal bacteriemia: the hospital or the home? A review of Staphylococcus aureus bacteraemia at Concord Hospital in 1993. Australian and New Zealand Journal of Medicine, 1998:28; 23.
13. National Committee for Clinical Laboratory Standards. Approved Standard M2-A5, M7-A3. 13, No 24 and 25. NCCLS. Villanova. PA. 2000.
14. Statisticals from Havana Hospitals: Gineco-Obstétrico América Arias, Pediatric “Juan M. Márquez”, ClinicChirurgical “Joaquín Albarrán” and CQF (1995-1997).
15. Martínez JA, Mensa J, Marco F, Almela M, López J, Casals C, Soriano E, Jiménez de Anta MT. Risk factors for oxacilina/methicillin resistance in coagulasenegative staphylococci. Journal of Hospital Infection 1997;35: 295.
16. Salisbury Steven M, Sabatini Linda M and Spiegel Carol A. Identification of Methicillin-Resistant Staphylococci by Multiplex Polymerase Chain Reaction Assay. American Journal of Clinical Pathology 1997;107: 368.
17. van Belkum A, et al. Polymerase chain reactionmediated typing of microorganisms: tracking dissemination of genes and genomes. Electrophoresis 1998;19: 602.
18. Herwaldt LA. Control of Methicillin-resistant Staphylococcus aureus in the hospital setting. American Journal of Medicine 1999;106: 11S.
19. Marty L, Jarlier V. Surveillance of multiresistance bacteria: justification, role of the laboratory, indicators and recent French data. Pathology and Biology (Paris) 1998;46: 217.
20. Amábile Cuevas CF, ed. Antibiotic Resistance: from Molecular Basis to Therapeutic Options. Chapman & Hall. Company Austin R. G. Landes. 1995:1-188.
21. Wenzel RP, Reagan DR, Bertino JS, Baron EJ, Arias K. Methicillin-resistant Staphylococcus aureus outbreak: a consensus panel’s definition and management guidelines. American Journal of Infection Control 1998;26:102.
22. Alexander Tomaz. Multiple-Antibiotic-Resistant Pathogenic Bacteria. A Report on the Rockefeller University Workshop. New England Journal of Medicine, 1994;330:1247.
23. Bradley SF. Methicillin-resistant Staphylococcus aureus: long term care concerns. American Journal of Medicine 1999;106: 2S.
24. Mikos-Schild S. MRSA-what every health care provider should know. Todays Surgical Nurse 1998;20: 20.
25. Monnet DL. Methicillin-resistant Staphylococcus aureus and its relationship to antimicrobial use: possible implications for control. Infection Control and Hospital Epidemiology 1998;19:552.
26. Cunha BA. Antibiotic resistance. Control strategies. Critical Care Clinics 1998;14:309.
27. Baquero F. Gram-positive resistance: challenge for the development of new antibiotics. Journal of Antimicrobial Chemotherapy 1997;39 (Suppl. A):1.
28. Ito T, Hiramatsu K. Acquisition of methicillin resistance and progression of multiantibiotic resistance in methicillinresistance. Yonsei Medical Journal 1998;39: 526.
29. Tambic A. Methicillin-resistant Staphylococcus aureus (MRSA), a predictor of the end of the antibiotic eradiagnosis, epidemiology, therapy and dissemination prevention. Lijecnicki Vjesnik 1997;119: 166.
30. Ehlert K. Methicillin-resistance in Staphylococcus aureus-molecular basis, novel targets and antibiotic therapy. Current Pharmaceutical Design, 1995;5:45.
31. Kim JM, Song YG. Vancomycin-resistant enterococcal infections in Korea. Yonsei Medical Journal 1998; 39:562.
32. Isolates of partially vancomycin-resistant S. aureus reported in United States. Findings follow similar report in Japan (Editorial). American Journal of Health-System Pharmacy 1997; 1: 2434.
33. Hanaki H, Hiramatsu K. Evaluation of reduced vancomycin susceptibility of MRSA strain Mu50 with various conditions of antibiotic susceptibility tests. Japanese Journal of Antibiotics 1997:50; 794.
34. Hiramatsu K, Aritaka N, Hanaki H, Kawasaki S, Hosoda Y, Hori S, Fukuchi Y, Kobayashi I. Dissemination in Japanese hospitals of strains of Staphylococcus aureus heterogeneously resistant to vancomycin. Lancet 1997;350:1670.
35. News. Staphylococcus aureus with reduced susceptibility to vancomycin-United States. MMWR. Morbidity and mortality weekly report 1997;46:813.
36. Tabaqchali S.Vancomycin-resistant Staphylococcus aureus: apocalypse now? Lancet 1997;6: 1644.
37. File TM. Overview of resistance in the 1990’s. Chesth, 1999;115: 3S.
38. Inoue M, Kuga A, Shimauchi C, Yano H, Oka-moto R. Why do antimicrobial agents become ineffectual? Yonsei Medical Journal 1998;39:502.
39. Brun-Buisson C. Methicillin-resistant Staphylococcus aureus: evolution and epidemiology, clinical impact, and prevention. Pathology and Biology (Paris) 1998;46: 227.