Acta Padiatr 81: 941-3. 1992
CASE REPORT
Chloramphenicol-resistant Haemophilus influenzae meningitis in young urban Nigerian children Abdul-Wahab BR Johnson, Olugbenga A Mokuolu and Boas A Onile' Departments of PaediatricslChild Health and Medical Microbiology/Parasitology' , University of Ilorin Teaching Hospital. Ilorin. Nigeria
Johnson A-WBR, Mokuolu OA, Onile BA. Chloramphenicol-resistant Haemophilus injluenzae meningitis in young urban Nigerian children. Acta Paediatr 1992;81 :941-3. Stockholm. ISSN 08035253 In a developing country like Nigeria, the unusual emergence of Haemophilus injluenzae type b, resistant to cost-effective antimicrobials, is of serious concern. We report three cases of H. injluenzae type b meningitis in young Nigerian children in whom clinical and bacteriological features of resistance to chloramphenicolwere identified. One of the cases had concomitant resistance to ampicillin (multipledrug resistance).Significant anaemia was an associated feature in two cases, one of whom had a recent measles infection. All three cases were malnourished. The possible mechanisms of antimicrobial resistance in H. injluenzae infections are highlighted while the need for periodic surveillance of antibiotic resistance profiles in resource-poor countries is emphasized. The potential value of prophylactic measures like H. injluenzae type b conjugate immunization is discussed. 0 Bacterial meningitis, chloramphenicol-resistant Hib, controllprophylaxis, developing world, Haemophilus influenzae type b (Hib), multiple-drug resistance A- WBR Johnson, Department of Child Health, Level G . Centre Block, Southampton General Hospital, Southampton SO9 4XY. UK. (Correspondence after January 10, 1993 to Department of Child Health, University of Ilorin, P M B 1515, Ilorin, Kwara State, Nigeria)
Haemophilus influenzae, especially the capsulated serotype b (Hib), remains a common cause of pyogenic meningitis worldwide (1-4). Besides the well known high case fatality, long-term morbidity, including blindness, deafness and other neurological deficits, may result from a belated or inappropriate therapy (3,5). Previous Third World reports have alluded to the rarity of chloramphenicol-resistant Hib and chloramphenicol remains a cost-effective therapy of invasive Hib diseases ( 5 , 6 ) . We report a cluster of chloramphenicol-resistant Hib meningitis occurring within a four-month period. These cases highlight the changing pattern of Hib antibiotic sensitivity in our environment.
Case reports Case 1 MD (10-month-old male) presented at the Emergency Paediatric Unit with a four-day history of fever and cough associated with convulsion. The social background was poor while the initial clinical evaluation showed an underweight infant with pallor, tachypnoea, coarse inspiratory crackles, signs of meningeal irritation and a bulging fontanelle. These symptoms, together with the preliminary CSF findings of a high protein concentration (1 00 mg/dl), pleocytosis (520 white cells/ mm3 with 60% polymorphs) and glucose concentration of 1.4 mol/l (blood glucose 10 mmol/l), prompted a working diagnosis of bronchopneumonia complicated by pyogenic meningitis. Initial treatment comprised six-
hourly iv crystalline penicillin (300 iu/kg/day), chloramphenicol I00 mg/kg/day, paraldehyde/phenobarbitone and packed cell transfusion. The absence of clinical improvement, including a swinging pyrexia in the subsequent 48-72 h was followed by the microbiological report of CSF isolates of multiply-resistant Hib. Standard bacteriological techniques, including serotyping (7), were used for identification, while sensitivity was determined using the disc diffusion technique with Staphylococcus aureus ATCC 25923 as control. The Oxoid sensitivity test agar (supplemented with factors V and X) was used. Antibiotics in the discs comprised 10 pg of chloramphenicol, 2 iu penicillin, 10 pg of tetracycline, 30 pg of cefriaxone, 10 pg of ceftazidime and 30 pg of cefuroxime. Although the minimal inhibitory concentrations were not estimated, the Hib was resistant to chloramphenicol and ampicillin, partially resistant to tetracycline but sensitive to the third-generation cephalosporins. Antibiotics were changed to 12-hourly iv ceftazidime (100 mg/kg/day), with subsequent remarkable clinical improvement and CSF sterilization with 12 days. The post-discharge evaluations showed no neurological sequelae.
Case 2 AF was admitted 10 weeks after Case 1. She was nine months old with poor social circumstances. Some six weeks before presentation, she had an exanthematous febrile illness (presumably measles), culminating in fever and convulsions for three weeks prior to admission.
942
A - WBR Johnson ef al.
Home remedies included native concorction and “therapeutic” incision marks over the bulging fontanelle. On admission, she looked toxic and pale in addition to features of marasmus. She was unconscious and was also opisthotonic. The lumbar CSF was purulent with elevated white cells (3200/mm3 with 72% polymorphs) and protein concentration (220 mg/dl) but a low glucose concentration (0.5 mmol/l). Anti-meningitic doses of crystalline penicillin and chloramphenicol were given (as specified for Case l), along with supportive care. Subdural tap suggested the presence of effusions. There was no clinical improvement after three days of treatment, when the CSF findings of chloramphenicolresistant but ampicillin-sensitive Hib, necessitated a change to six-hourly iv ampicillin (400 mg/kg/day). The microbiological techniques used were the same in Case 1. Despite CSF sterilization and a clearer sensorium after 14 days of this therapy, neurological sequelae, including blindness, inability to sit unsupported and loss of head control, were evident at the only outpatient evaluation, four weeks post-discharge. Case 3 TM, who presented six weeks after AF, was a 19-monthold toddler with a five-day history of fever and cough, associated with neck retraction in the preceding 24 h. He also had a poor social background and was small for his age on admission. Other findings included prostration, meningeal signs, spasticity and lumbar CSF findings of pyogenic meningitis. Again, high dose iv crystalline penicillin and chloramphenicol were initiated as “blind” therapy. The persistence of a swinging pyrexia and the appearance of a right-sided facial nerve palsy, led us to change antimicrobial therapy on the third day to 12hourly iv cefriaxone (1 00 mg/kg/day)and 6-hourly iv ampicillin (400 mg/kg/day). Chloramphenicol-resistant but ampicillin-sensitive Hib was isolated on the fifth day by the same laboratory that reported drug resistance in the two previous cases. At this point, iv ampicillin was continued to complete two weeks of inpatient treatment, after which CSF sterilization was confirmed. Follow-up evaluations showed no neurological sequelae.
Discussion Along with Staphylococcus pneumoniae and Neisseria meningitides, Hib remains a common cause of childhood meningitis in developing countries (3-6). In resourcepoor countries, where facilities for laboratory diagnosis may be inadequate, prompt and appropriate empirical treatment, based on current patterns of sensitivity, is crucial to a favourable disease outcome. Furthermore, the frequent non-availability of laboratory confirmation of the aetiology remains a justification for continuing the initial drugs for the entire course (2, 5 , 6). Some of the previous reports from tropical Africa (4-6), have addressed the issue of sensitivity/resistance profiles of bacterial meningitides but the need for up-to-date
ACTA PRDIATR 8 I (1 992)
information is self-evident. The current report is intended to draw attention to the occurrence of chloramphenicol-resistant Hib in Nigeria, as an example of the increase in the prevalence of multi-drug resistant strains with the anticipated economic burden of altered (empirical) antimicrobial policies. Two of the cases illustrate the reported frequent association of Hib meningitis with repiratory infections ( 5 , 8). Similarly, the clinical presentations of these children exemplify the reported vulnerability of the malnourished infant with poor social circumstances and intercurrent infections (3, 5 , 9). From the clinician’s viewpoint, the crucial initial decision is not so much the prediction of the bacterial pathogen, but a timely recognition of the often non-specific features of pyogenic meningitis in early childhood and hence the prompt initiation of empirical antimicrobials. Case 2 illustrates the neurological consequence of a belated treatment, while the importance of a timely anticipation of antimicrobial resistance is exemplified by the excellent outcome of the disease in Case 3. Chloramphenicol-resistant Hib, with or without concomitant ampicillin resistance, has been reported in the developed world (10-14). In some of these reports (10, 11, 13), the rarity of multi-drug resistant strains was highlighted. However, the Spanish report from Barcelona (14), recorded multi-drug resistance in as many as 57% of isolates. Like ampicillin resistance, which is associated with beta-lactamase production, resistance to chloramphenicol is mediated by bacterial elaboration of chloramphenicol acetyl transferase (1 5 , 16). A common plasmid may code for resistance to ampicillin, chloramphenicol and tetracycline (16). This is an accord with the findings of Campos et al. (14), as well as the Hib sensitivity pattern in our subject with multiple resistance. It would, however, not explain the intra-regional disparity between the prevalence of ampicillin-resistance and that of chloramphenicol-resistance. Unlike chloramphenicol-resistancewhich remains less than 1 % (1 l), the current prevalence of ampicillin-resistant Hib is 21 % in the USA (17). On the other hand, 1 1.4% of CSF isolates in children with H. influenzae meningitis at the University College Hospital, Ibadan, Nigeria, were reportedly resistant to ampicillin, while no case of chloramphenicol resistance was recorded over four years ( 5 ) . This contrasted with a prevalence of 25% for chloramphenicol-resistant CSF strains of S.pneumoniae in the same report (5). Furthermore, our local laboratory records of childhood meningitides (at the University of Ilorin Teaching Hospital), in the five years antedating the current cluster of cases, showed no case of Hib-related chloramphenicol/multiple resistance. Previous African series (4, 6, 18) had also observed the rarity of chloramphenicol-resistant H. influenzae meningitis, but a recent retrospective review (1985- 1990) of CSF isolates in another urban Nigerian community (Benin-City, unpublished), recorded four cases (13%) with multiple-drug resistance. Indiscriminate use of
-
ACTA PEDIATR 81 (1992)
antibiotics, especially in our urban populations (19), may account for the emergence of these drug-resistant strains. In Nigeria and East Africa (5,6), the current empirical treatment of pyogenic meningitis remains chloramphenicol (to cover a possible Hib aetiology) and crystalline penicillin (for meningococcus and pneumococcus): penicillin-resistant pneumococci are still rare in these regions (5,6). While a suboptimal efficacy-for treating Hib meningitis-has been suggested for the alternative combination of ampicillin and chloramphenicol (20, 2 I), the current cluster of drug-resistant cases underscores the need for local periodic surveillance of antimicrobial sensitivity profiles of the common bacterial meningitides. In Nigeria, and presumably other tropical countries, it would be premature to recommend a change in the current cost-effectiveempirical therapy ( 5 , 6), especially in view of the financial cost to parents who usually bear the costs of treatment in these countries. This is in contrast to the developed world, where the relatively expensive third-generation cephalosporins (which we were compelled to use in two of the cases), are now recommended for routine treatment of invasive Hib infections (22, 23). Finally, the emergence of multi-drug resistant Hib in resource-poor countries calls for additional control measures. Besides the need for legislative measures to streamline a rational sale/use of antibiotics, the potential value of Hib conjugate vaccination is great (1 2, 24, 25). That the vaccine may be safely administered with the diphtheria, pertussis, tetanus toxoid and oral polio (1 8,24,25) of the current WHO expanded programme on immunization (which has proved successful to date in the West African subregion), is clearly an asset in the developing world. Rifampicin chemoprophylaxis has been recommended (26), but besides the cost, widespread resistance (not only to Hib, but also the Mycobacterium tuberculosis) is a distinct possibility. The experience with meningococcal chemoprophylaxis with the same agent (8, 27), is an eye opener! Acknowledgements.-The authors acknowledge with thanks the microbiological inputs of Mr Chuks Nwofor and D r BO Ogunbanjo. The correspondence author is particularly indebted to Dr CR Kennedy, Consultant Paediatric Neurologist (Southampton General Hospital, UK) and Professor DG Montefiore, FRCPath, OBE, for their critical review of the manuscript. Finally, the authors thank the Chief Medical Director of the hospital (for waiving the costs of the ceftazidime and cefriaxone with which two of the cases were treated) and Mrs Brenda Colwell, for secretarial service.
References I . Schlech WF 111, Ward JI, Hightower A, Fraser DW, Broome CV. Bacterial meningitis in the United States-1978 through 1981. JAMA 1985;253:1749-54 2. Goldcare MJ. Acute meningitis in childhood: Incidence and mortality in defined population. Lancet 1976;i:28-32 3. Hailemeskel H, Tafari N. Bacterial meningitis in childhood in an African city: factors influencing aetiology and outcome. A d a Paediatr Scand 1978;67:725-30 4. Montefiore DG, Alausa OK, Sobayo E. Pyogenic meningitis in Ibadan, Nigeria. Scand J Infect Dis 1978;10:113-I8
Chloramphenicol-resistantHib meningitis in Nigeria
943
5 . Nottidge VA. Haemophilusinfluenzaemeningitis: a 5-year study in
Ibadan, Nigeria. J Infect 1985;11:109-17 6. Hadgu P, Tafari N. Results of current therapy for pyogenic meningitis in children. Ethiop Med J 1973;1:67-73 7. Kilian M. Haemophilus. In: Lennette EH, Balows A, Hausler WJ Jr, Shadomy HJ eds Manual of Clinical Microbiology 4th Edn. Washington DC: American Society for Microbiology, 1985:38793 8. Feigin RD. Acute bacterial meningitis beyond the neonatal period. In: Behrman RE, Vaughan Ill VC eds Nelson Textbook of Paediatrics 13th Edn. Philadelphia: WB Saunders, 1987:569-73 9. Fraser DW, Darby CP, Koehler RE, Jacobs CF, Feldman RA. Risk factors in bacterial meningitis: Charlston Country, South Carolina. J Infect Dis 1973;127:271-7 10. Powell M, Koutsia-Carouzou C, Voutsinas D, Seymour A, Williams JD. Resistance of clinical isolates of Haemophilus influenzae in United Kingdom 1986. BMJ 1987;295:176-9 1 I . Doern GV, Jorgensen JH, Thornsberry C, et al. National collaborative study of the prevalence of antimicrobial resistance among clinical isolates of Haemophilus influenzae. Antimicrob Agents Chemother 1988;32:180-5 12. Jenner BM, Williamson G, Luppino M. Fatal meningitis caused by chloramphenicol-resistant Haemophilusinfluenzae. Med J Aust 1990;152:335-6 13. Manten A, Van-Kingeren B, Dessens-Kroon M. Chloramphenicol resistance in Haemophilus influenzae. Lancet 1976;i:702 4. Campos J, Garcia-Tornel S , Sanfeliu I. Susceptibility studies of multiply resistant Haemophilus influenzaeisolated from paediatric patients and contacts. Antimicrob Agents Chemother 1984;25: 706-9 5. Powell M. Antimicrobial resistance in Haemophilus influenzae. J Med Microbiol 1988;27:81-7 6. Roberts MC, Swenson CD, Owens LM. Smith AL. Characterisation of chloramphenicol-resistant Haemophilus influenrue. Antimicrob Agents Chemother l980;18:610-15 17. Doern GV, Jorgerson JH, Thornsberry C, Preston DA. The Haemophilus influenzae Surveillance Group. Prevalence of antimicrobial resistance among clinical isolates of Haemophilus influenzae: a collaborative study. Diagn Microbiol Infect Dis 1986;495-107 18. Ogunbanjo BO. Haemophilus influenzae infections in Ibadan, Nigeria. FMCPath dissertation, 1984;140pp 19. Anya IM, Oyewole AO. Akinwolere AOA. Use and misuse of drugs in Nigerian infants. Nig Med J 1987;17:21-9 20. Linberg J, Rosenhall U, Nylen 0, Rigner A. Longterm outcome of Haemophilus influenzae meningitis related to antibiotic treatment. Pediatrics 1977;60:1-6 21. Mackenzie AMR, Chan FTH. Combined action of chloramphenicol and ampicillin on chloramphenicol-resistant Haemophilus influenzae. Antimicrob Agents Chemother 1986;29:565-9 22. Report from a Swedish study group: Cefuroxime versus ampicillin and chloramphenicol for the treatment of bacterial meningitis. Lancet 1982;i:295-9 23. Committee on Infectious Diseases, American Academy of Pediatrics. Treatment of bacterial meningitis. Pediatrics 1988;81:9047 24. Immunisation Practices Advisory Committee. Haemophilus b conjugate vaccines for the prevention of Haemophilus influenzae type b disease amongst infants and children 2 months of age and older. Recommendations of the immunisation Practices Advisory Committee (A.C.I.P.). MMWR 1991;40:1-7 25. Booy R, Taylor SA, Dobson SRM, et al. Immunogenicity and safety of PRP-T conjugate vaccine given according to the British accelerated immunisation schedule. Arch Dis Child 1992;67:6758 26. Committee on Infectious Diseases, 1984. Revision of recommendations for the use of rifampicin prophylaxis of contacts of patients with Haemophilus influenzae infections. Pediatrics 1984;74301 27. Christie AB. Infectious Diseases-Epidemiology and Clinical Practice 3rd Edn. Edinburgh: Churchill Livingstone, 1980:630 Received Nov. 5 . 1991. Accepted Aug. 8, 1992
CASE REPORT
Chloramphenicol-resistant Haemophilus influenzae meningitis in young urban Nigerian children Abdul-Wahab BR Johnson, Olugbenga A Mokuolu and Boas A Onile' Departments of PaediatricslChild Health and Medical Microbiology/Parasitology' , University of Ilorin Teaching Hospital. Ilorin. Nigeria
Johnson A-WBR, Mokuolu OA, Onile BA. Chloramphenicol-resistant Haemophilus injluenzae meningitis in young urban Nigerian children. Acta Paediatr 1992;81 :941-3. Stockholm. ISSN 08035253 In a developing country like Nigeria, the unusual emergence of Haemophilus injluenzae type b, resistant to cost-effective antimicrobials, is of serious concern. We report three cases of H. injluenzae type b meningitis in young Nigerian children in whom clinical and bacteriological features of resistance to chloramphenicolwere identified. One of the cases had concomitant resistance to ampicillin (multipledrug resistance).Significant anaemia was an associated feature in two cases, one of whom had a recent measles infection. All three cases were malnourished. The possible mechanisms of antimicrobial resistance in H. injluenzae infections are highlighted while the need for periodic surveillance of antibiotic resistance profiles in resource-poor countries is emphasized. The potential value of prophylactic measures like H. injluenzae type b conjugate immunization is discussed. 0 Bacterial meningitis, chloramphenicol-resistant Hib, controllprophylaxis, developing world, Haemophilus influenzae type b (Hib), multiple-drug resistance A- WBR Johnson, Department of Child Health, Level G . Centre Block, Southampton General Hospital, Southampton SO9 4XY. UK. (Correspondence after January 10, 1993 to Department of Child Health, University of Ilorin, P M B 1515, Ilorin, Kwara State, Nigeria)
Haemophilus influenzae, especially the capsulated serotype b (Hib), remains a common cause of pyogenic meningitis worldwide (1-4). Besides the well known high case fatality, long-term morbidity, including blindness, deafness and other neurological deficits, may result from a belated or inappropriate therapy (3,5). Previous Third World reports have alluded to the rarity of chloramphenicol-resistant Hib and chloramphenicol remains a cost-effective therapy of invasive Hib diseases ( 5 , 6 ) . We report a cluster of chloramphenicol-resistant Hib meningitis occurring within a four-month period. These cases highlight the changing pattern of Hib antibiotic sensitivity in our environment.
Case reports Case 1 MD (10-month-old male) presented at the Emergency Paediatric Unit with a four-day history of fever and cough associated with convulsion. The social background was poor while the initial clinical evaluation showed an underweight infant with pallor, tachypnoea, coarse inspiratory crackles, signs of meningeal irritation and a bulging fontanelle. These symptoms, together with the preliminary CSF findings of a high protein concentration (1 00 mg/dl), pleocytosis (520 white cells/ mm3 with 60% polymorphs) and glucose concentration of 1.4 mol/l (blood glucose 10 mmol/l), prompted a working diagnosis of bronchopneumonia complicated by pyogenic meningitis. Initial treatment comprised six-
hourly iv crystalline penicillin (300 iu/kg/day), chloramphenicol I00 mg/kg/day, paraldehyde/phenobarbitone and packed cell transfusion. The absence of clinical improvement, including a swinging pyrexia in the subsequent 48-72 h was followed by the microbiological report of CSF isolates of multiply-resistant Hib. Standard bacteriological techniques, including serotyping (7), were used for identification, while sensitivity was determined using the disc diffusion technique with Staphylococcus aureus ATCC 25923 as control. The Oxoid sensitivity test agar (supplemented with factors V and X) was used. Antibiotics in the discs comprised 10 pg of chloramphenicol, 2 iu penicillin, 10 pg of tetracycline, 30 pg of cefriaxone, 10 pg of ceftazidime and 30 pg of cefuroxime. Although the minimal inhibitory concentrations were not estimated, the Hib was resistant to chloramphenicol and ampicillin, partially resistant to tetracycline but sensitive to the third-generation cephalosporins. Antibiotics were changed to 12-hourly iv ceftazidime (100 mg/kg/day), with subsequent remarkable clinical improvement and CSF sterilization with 12 days. The post-discharge evaluations showed no neurological sequelae.
Case 2 AF was admitted 10 weeks after Case 1. She was nine months old with poor social circumstances. Some six weeks before presentation, she had an exanthematous febrile illness (presumably measles), culminating in fever and convulsions for three weeks prior to admission.
942
A - WBR Johnson ef al.
Home remedies included native concorction and “therapeutic” incision marks over the bulging fontanelle. On admission, she looked toxic and pale in addition to features of marasmus. She was unconscious and was also opisthotonic. The lumbar CSF was purulent with elevated white cells (3200/mm3 with 72% polymorphs) and protein concentration (220 mg/dl) but a low glucose concentration (0.5 mmol/l). Anti-meningitic doses of crystalline penicillin and chloramphenicol were given (as specified for Case l), along with supportive care. Subdural tap suggested the presence of effusions. There was no clinical improvement after three days of treatment, when the CSF findings of chloramphenicolresistant but ampicillin-sensitive Hib, necessitated a change to six-hourly iv ampicillin (400 mg/kg/day). The microbiological techniques used were the same in Case 1. Despite CSF sterilization and a clearer sensorium after 14 days of this therapy, neurological sequelae, including blindness, inability to sit unsupported and loss of head control, were evident at the only outpatient evaluation, four weeks post-discharge. Case 3 TM, who presented six weeks after AF, was a 19-monthold toddler with a five-day history of fever and cough, associated with neck retraction in the preceding 24 h. He also had a poor social background and was small for his age on admission. Other findings included prostration, meningeal signs, spasticity and lumbar CSF findings of pyogenic meningitis. Again, high dose iv crystalline penicillin and chloramphenicol were initiated as “blind” therapy. The persistence of a swinging pyrexia and the appearance of a right-sided facial nerve palsy, led us to change antimicrobial therapy on the third day to 12hourly iv cefriaxone (1 00 mg/kg/day)and 6-hourly iv ampicillin (400 mg/kg/day). Chloramphenicol-resistant but ampicillin-sensitive Hib was isolated on the fifth day by the same laboratory that reported drug resistance in the two previous cases. At this point, iv ampicillin was continued to complete two weeks of inpatient treatment, after which CSF sterilization was confirmed. Follow-up evaluations showed no neurological sequelae.
Discussion Along with Staphylococcus pneumoniae and Neisseria meningitides, Hib remains a common cause of childhood meningitis in developing countries (3-6). In resourcepoor countries, where facilities for laboratory diagnosis may be inadequate, prompt and appropriate empirical treatment, based on current patterns of sensitivity, is crucial to a favourable disease outcome. Furthermore, the frequent non-availability of laboratory confirmation of the aetiology remains a justification for continuing the initial drugs for the entire course (2, 5 , 6). Some of the previous reports from tropical Africa (4-6), have addressed the issue of sensitivity/resistance profiles of bacterial meningitides but the need for up-to-date
ACTA PRDIATR 8 I (1 992)
information is self-evident. The current report is intended to draw attention to the occurrence of chloramphenicol-resistant Hib in Nigeria, as an example of the increase in the prevalence of multi-drug resistant strains with the anticipated economic burden of altered (empirical) antimicrobial policies. Two of the cases illustrate the reported frequent association of Hib meningitis with repiratory infections ( 5 , 8). Similarly, the clinical presentations of these children exemplify the reported vulnerability of the malnourished infant with poor social circumstances and intercurrent infections (3, 5 , 9). From the clinician’s viewpoint, the crucial initial decision is not so much the prediction of the bacterial pathogen, but a timely recognition of the often non-specific features of pyogenic meningitis in early childhood and hence the prompt initiation of empirical antimicrobials. Case 2 illustrates the neurological consequence of a belated treatment, while the importance of a timely anticipation of antimicrobial resistance is exemplified by the excellent outcome of the disease in Case 3. Chloramphenicol-resistant Hib, with or without concomitant ampicillin resistance, has been reported in the developed world (10-14). In some of these reports (10, 11, 13), the rarity of multi-drug resistant strains was highlighted. However, the Spanish report from Barcelona (14), recorded multi-drug resistance in as many as 57% of isolates. Like ampicillin resistance, which is associated with beta-lactamase production, resistance to chloramphenicol is mediated by bacterial elaboration of chloramphenicol acetyl transferase (1 5 , 16). A common plasmid may code for resistance to ampicillin, chloramphenicol and tetracycline (16). This is an accord with the findings of Campos et al. (14), as well as the Hib sensitivity pattern in our subject with multiple resistance. It would, however, not explain the intra-regional disparity between the prevalence of ampicillin-resistance and that of chloramphenicol-resistance. Unlike chloramphenicol-resistancewhich remains less than 1 % (1 l), the current prevalence of ampicillin-resistant Hib is 21 % in the USA (17). On the other hand, 1 1.4% of CSF isolates in children with H. influenzae meningitis at the University College Hospital, Ibadan, Nigeria, were reportedly resistant to ampicillin, while no case of chloramphenicol resistance was recorded over four years ( 5 ) . This contrasted with a prevalence of 25% for chloramphenicol-resistant CSF strains of S.pneumoniae in the same report (5). Furthermore, our local laboratory records of childhood meningitides (at the University of Ilorin Teaching Hospital), in the five years antedating the current cluster of cases, showed no case of Hib-related chloramphenicol/multiple resistance. Previous African series (4, 6, 18) had also observed the rarity of chloramphenicol-resistant H. influenzae meningitis, but a recent retrospective review (1985- 1990) of CSF isolates in another urban Nigerian community (Benin-City, unpublished), recorded four cases (13%) with multiple-drug resistance. Indiscriminate use of
-
ACTA PEDIATR 81 (1992)
antibiotics, especially in our urban populations (19), may account for the emergence of these drug-resistant strains. In Nigeria and East Africa (5,6), the current empirical treatment of pyogenic meningitis remains chloramphenicol (to cover a possible Hib aetiology) and crystalline penicillin (for meningococcus and pneumococcus): penicillin-resistant pneumococci are still rare in these regions (5,6). While a suboptimal efficacy-for treating Hib meningitis-has been suggested for the alternative combination of ampicillin and chloramphenicol (20, 2 I), the current cluster of drug-resistant cases underscores the need for local periodic surveillance of antimicrobial sensitivity profiles of the common bacterial meningitides. In Nigeria, and presumably other tropical countries, it would be premature to recommend a change in the current cost-effectiveempirical therapy ( 5 , 6), especially in view of the financial cost to parents who usually bear the costs of treatment in these countries. This is in contrast to the developed world, where the relatively expensive third-generation cephalosporins (which we were compelled to use in two of the cases), are now recommended for routine treatment of invasive Hib infections (22, 23). Finally, the emergence of multi-drug resistant Hib in resource-poor countries calls for additional control measures. Besides the need for legislative measures to streamline a rational sale/use of antibiotics, the potential value of Hib conjugate vaccination is great (1 2, 24, 25). That the vaccine may be safely administered with the diphtheria, pertussis, tetanus toxoid and oral polio (1 8,24,25) of the current WHO expanded programme on immunization (which has proved successful to date in the West African subregion), is clearly an asset in the developing world. Rifampicin chemoprophylaxis has been recommended (26), but besides the cost, widespread resistance (not only to Hib, but also the Mycobacterium tuberculosis) is a distinct possibility. The experience with meningococcal chemoprophylaxis with the same agent (8, 27), is an eye opener! Acknowledgements.-The authors acknowledge with thanks the microbiological inputs of Mr Chuks Nwofor and D r BO Ogunbanjo. The correspondence author is particularly indebted to Dr CR Kennedy, Consultant Paediatric Neurologist (Southampton General Hospital, UK) and Professor DG Montefiore, FRCPath, OBE, for their critical review of the manuscript. Finally, the authors thank the Chief Medical Director of the hospital (for waiving the costs of the ceftazidime and cefriaxone with which two of the cases were treated) and Mrs Brenda Colwell, for secretarial service.
References I . Schlech WF 111, Ward JI, Hightower A, Fraser DW, Broome CV. Bacterial meningitis in the United States-1978 through 1981. JAMA 1985;253:1749-54 2. Goldcare MJ. Acute meningitis in childhood: Incidence and mortality in defined population. Lancet 1976;i:28-32 3. Hailemeskel H, Tafari N. Bacterial meningitis in childhood in an African city: factors influencing aetiology and outcome. A d a Paediatr Scand 1978;67:725-30 4. Montefiore DG, Alausa OK, Sobayo E. Pyogenic meningitis in Ibadan, Nigeria. Scand J Infect Dis 1978;10:113-I8
Chloramphenicol-resistantHib meningitis in Nigeria
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5 . Nottidge VA. Haemophilusinfluenzaemeningitis: a 5-year study in
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