Neisseria meningitidis ANTIMICROBIAL RESISTANCE:CURRENT SITUATION IN LATIN AMERICA AND ITS CLINICAL RELEVANCE Dra. Silvia E. González Ayala Head Professor Cátedra Infectología, Facultad Ciencias Médicas, Universidad Nacional La Plata Head Professor, Cátedra Infectología, Escuela Superior de Ciencias de la Salud, Universidad Nacional del Centro de la Provincia de Buenos Aires Consult Professor for Pediatric Infectious Diseases, Hospital de Niños Superiora Sor María Ludovica
Invasive meningococcal disease is severe and rapidly progressing illness. Inmediate management with effective antibotics and chemoprophylaxis must be administered
Agenda History Projects PAHO/WHO Situation in Latin American countries Closing remarks
Agenda History Projects PAHO/WHO Situation in Latin American countries Closing remarks
History 1985 (Spain): first isolates with a decreased susceptibility to penicillin 90s: USA, Canada, Italy, Greece, UK, France, Israel, and Australia Mechanisms altered forms of PBP2 (pena) beta lactamase production decrease membrane permeability efflux pump Sáez-Nieto JA, et al. Clin Infect Dis 1992; 14:394-402 Oppenheim BA. Clin Infect Dis 1997; 24 (Suppl1):S98-101 Vázquez JA, et al. Rev Med Microbiol 2001; 12: 39-45
History 1987 (Vietnam): first isolate with high resistance to chloramfenicol Australia, France, and Vietnam Mechanism catp gene encoding enzyme Chloramfenicol acetyltransferase Larkin M. Lancet 1998; 352;1123 Schultz TR, et al. J Antimicrob Chemother 2003; 52:856-859 Galimand M, et al. N Engl J Med 1998; 339:868-874
History 2005 (India): first isolates non-susceptible to ceftriaxone Manchanda V, et al. J Clin Microbiol 2006; 44:4290-4291
History 60s: first isolates with a rifampicin-resistant menigococci USA, France and Australia Mechanism aminoacid sustitutions (rpob gene) codons: Asp542, Ser548, His552, Ser557, Gly560 Carter PE, et al. Antimicrob Agents Chemother 1994; 38:1256-1261 Nolte O. Antimicrob Agents Chemother 1997; 39:747-755 Rainbow J, et al. Emerg Infect Dis 2005; 11:977-979 Taha MK. Emerg Infect Dis 2006; 12:859-860 Neri A, et al. BMC Microbiology 2010;10.246
History 1992 (Greece): first isolate with a decreased susceptibility to ciprofloxacin Argentina, and USA Mechanisms Australia, Hong Kong, India, Italy, quinolone resistance determining region (QRDR) (gyra, parc genes) = amino acids sustitutions Alcalá B, et al. J Antimicrob Chemother 2004; 53:409 Corso A, et al. J Antimicrob Chemother 2005; 55:596-597 Singhal S, et al. Emerg Infect Dis 2007; 13:614-616 CDC. MMWR Morb Mortal kly Rep 2008; 57:173-175 Skocynska A, et al. Emerg Infect Dis 2008; 14:1322-1323 Lapadula G, et al. Emerg Infect Dis 2009; 1852-1853 Wu HM. N Engl J Med 2009; 360:886-892
History 1992 (Greece): first isolate with a decreased susceptibility to ciprofloxacin Argentina, and USA Mechanisms Australia, Hong Kong, India, Italy, quinolone resistance determining region (QRDR) (gyra, parc genes) = amino acids sustitutions Alcalá B, et al. J Antimicrob Chemother 2004; 53:409 Corso A, et al. J Antimicrob Chemother 2005; 55:596-597 Singhal S, et al. Emerg Infect Dis 2007; 13:614-616 CDC. MMWR Morb Mortal kly Rep 2008; 57:173-175 Skocynska A, et al. Emerg Infect Dis 2008; 14:1322-1323 Lapadula G, et al. Emerg Infect Dis 2009; 1852-1853 Wu HM. N Engl J Med 2009; 360:886-892
Agenda History Projects PAHO/WHO Situation in Latin American countries Closing remarks
PROJECTS PAHO/WHO 1993: SIREVA network launched 2010: Project to improve surveillance and characterization of meningococcal disease in the Latin American Region (HSD/PAHO/WHO): multilocus sequence typing, real time-pcr) A multiyear initiative to promote evidence-based policy decisions regarding the introduction of new vaccines in Latin America and the Caribbean
Agenda History Projects PAHO/WHO Situation in Latin American countries Closing remarks
Situation in Latin American Antibiotic countries Break points European Monitoring Group on Meningococci (EMGM) Susceptible/resistant ug/ml Penicillin < 0.06 / > 1 Ampicillin < 0.12 / > 2 Ciprofloxacin < 0.03 / > 0.5 Chloramphenicol < 2 / > 8 Ceftriaxone < 0.12 / Rifampicin < 0.25 / > 2 Vázquez A. FEMS Microbiol Rev 2007; 31:97-100
Situation in Latin American countries Resistance to penicillin and therapeutic failure Few reports (1970 2005) 1994: Costa Rica, serogroup B (CIM 4ug/mL) 1993: Argentina, serogroup C (CIM 0,5 ug/ml) Herrera M, et al. Rev Med Hosp Nac Niños Dr. C Sáenz Herrera1995; 30:1-2 Bardi L, et al. Medicina (Buenos Aires) 1994; 54:427-430
Situation in Latin American Country / Age group (years) countries Percentage for intermediate susceptibility to penicillin of N. meningitidis strains isolated from invasive disease/age group/selected countries, 2000-2005 < 1 1-5 12-14 15 20 >20 Argentina 68.4 67.4 68.4 80 51.4 Brasil 4.2 5.5 4.7 4.1 5.2 Chile 64.7 33.3 63 76.6 58.4 Colombia 2.2 12.8 13.9 18.2 11.4 Gabastou JM, et al. Rev Panam Salud Pública 2008; 24:1-15
Situation in Latin American Country / Age group (years) countries Percentage for intermediate susceptibility to penicillin of N. meningitidis strains isolated from invasive disease/age group/selected countries, 2000-2005 < 1 1-5 12-14 15 20 >20 Cuba 50 30.8 50 66.7 25 Mexico 12.5 0 0 22.2 28.6 Uruguay 40 43.4 39.6 35.3 34 Venezuela 44.4 15 38.5 14.3 14.3 Gabastou JM, et al. Rev Panam Salud Pública 2008; 24:1-15
Situation in Latin American countries Intermediate susceptibility of N. meningitidis strains (n=1096) to penicillin according to gender, 2006 2008, Brazil Female: 14.3% Male: 12% Total: 13% Gorla MCO, et al. Enferm Infecc Microbiol Clin 2011; 29:85-89
Situation in Latin American countries Intermediate susceptibility of N. meningitidis strains (n=1096) to penicillin according to serogroups, 2006 2008, Brazil B: 13.4% C: 13.3% W135: 8.3% Y: 13.3% Total: 13% Gorla MCO, et al. Enferm Infecc Microbiol Clin 2011; 29:85-89
Situation in Latin American Country / Age group (years) n I countries Percentage for intermediate susceptibility and high resistance to penicillin, rifampicin, and ciprofloxacin of N. meningitidis strains isolated from invasive disease/age group/selected countries, SIREVA, 2010 Pen R I Rifam R I Cipro R Argentina 130 35.4 1.5 Brasil 506 12.6 0.6 0.2 Chile 56 80.4 NA Colombia 17 29.4 Gabastou JM, et al. Rev Panam Salud Pública 2008; 24:1-15
Situation in Latin American Country / Age group (years) n I countries Percentage for intermediate susceptibility and high resistance to penicillin, rifampicin, and ciprofloxacin of N. meningitidis strains isolated from invasive disease/age group/selected countries, SIREVA, 2010 Pen R I Rifam R I Cipro R Cuba 6 16.7 16.7 1.5 Mexico 17 82.4 Uruguay 20 50 10 Venezuela 11 36.4 Gabastou JM, et al. Rev Panam Salud Pública 2008; 24:1-15
Situation in Latin American Rifampicin countries 2010 (Montevideo, Uruguay): 2 isolates B:2a:P1.5 resistant The finding has been sporadic so far, unless a secondary case is identified, there is no justification to change the drug currently being administered to contacts as chemoprophylaxis Pérez Giffoni G, et al. Rev Panam Salud Pública 2011; 30:540-544
Situation in Latin American Ciprofloxacin countries The drug should no longer be prescribed for empiric chemoprophylaxis in areas where resistance was identified. CDC. MMWR Morb Mortal Wkly Rep 2008; 57:173-175
Agenda History Projects PAHO/WHO Situation in Latin American countries Closing remarks
Closing remarks Need of a deaper understanding of the interplay between antibiotic resistance, biological fitness and virulence There is no global alert for the spread of resistant N. meningitidis strains Isolates with reduce susceptibility to penicillin led clinicians to use third-generation cephalosporin for initial treatment
Closing remarks Continued surveillance for resistance to detect changes in the susceptibility to drugs use in treatment or chemoprophylaxis is useful The emergence of resistance is correlated to the outcome and successful management of close contacts