Antibiotic Resistance Among Nasopharyngeal Isolates of Streptococcus pneumoniae and Haemophilus influenzae -- Bangui, Central African Republic, 1995

Approximately 4 million children aged less than 5 years die worldwide each year from acute respiratory infections (ARI), most of which are pneumonia (1). Most pneumonia deaths result from bacterial infections, and Streptococcus pneumoniae (SP) and Haemophilus influenzae (HI) are the most common bacterial etiologies (1). To provide data about antibiotic resistance and to assist the National ARI Control Program of the Central African Republic (CAR) (1995 population: 2.9 million) in choosing which antibiotics to recommend for the treatment of pneumonia in children aged less than 5 years, a survey of the antibiotic resistance of nasopharyngeal (NP) isolates of SP and HI cultured from children residing in Bangui (1995 population: 451,000), CAR, was conducted during January 16-February 8, 1995, by the Ministry of Public Health and Population (MOPHP) in collaboration with epidemiologists from CDC and microbiologists from the South African Institute for Medical Research. Bangui is the capital of and the largest city in CAR. The decision to measure resistance rates among NP isolates was based on the results of a study indicating that resistance rates of SP and HI isolates cultured from NP swabs were similar to rates measured among isolates cultured from blood (2). This report summarizes the results of that survey, which indicated that SP and HI had relatively low resistance rates to penicillin, ampicillin, cotrimoxazole (trimethoprim-sulfamethoxazole), and chloramphenicol.

Specimens for culture were obtained from 371 consecutive children who received consultation for any illness at two outpatient clinics in Bangui. In addition, to determine resistance rates in a population at higher risk for carriage of a resistant organism, specimens were obtained from 35 children hospitalized on an inpatient ward. NP cultures of the 371 outpatients yielded 272 SP isolates and 73 HI isolates. NP cultures of the 35 inpatients yielded 17 SP isolates and eight HI isolates. The study was conducted during the dry season and the period of peak pneumonia incidence in CAR.

Among outpatients, resistance rates for NP cultures were relatively low for ampicillin, penicillin, and cotrimoxazole (Table_1): 8.8% of SP isolates were resistant to penicillin, and 6.3% were resistant to cotrimoxazole. Among HI isolates, 1.4% were resistant to ampicillin, and 12.3% were resistant to cotrimoxazole; no beta-lactamase were resistant to chloramphenicol, and no HI isolates were resistant to chloramphenicol. Although SP resistance to tetracycline was high (42.3%), this antibiotic has not been recommended for children, and no recent tetracycline use was documented in this survey population. SP resistance was not documented for erythromycin, rifampicin, or clindamycin -- drugs used infrequently in Central African children.

SP resistance rates to penicillin, cotrimoxazole, tetracycline, and chloramphenicol were higher among inpatients compared with outpatients (Table_1). In contrast, none of the HI isolates cultured from inpatients was resistant to ampicillin, cotrimoxazole, or chloramphenicol (Table_1).

Reported by: J Ndoyo, MD, RM Siopathis, MD, Ministry of Population and Public Health, Central African Republic. KP Klugman, MD, A Wasas, MT, Medical Research Council and Univ of the Witwatersrand Pneumococcal Diseases Research Unit, South African Institute for Medical Research, Johannesburg, South Africa. Childhood and Respiratory Diseases Br, Div of Bacterial and Mycotic Diseases; International Child Survival and Emerging Infections Program Support Activity, Div of Parasitic Diseases, National Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: To reduce ARI deaths among children, the World Health Organization (WHO) recommends that children aged less than 5 years with clinical signs of pneumonia be treated empirically with an antibiotic that has activity against SP and HI (1). Antibiotic resistance may decrease the clinical effectiveness of antibiotics used to treat pneumonia. The occurrence of SP and HI antibiotic resistance is a particular challenge for developing countries that can only afford inexpensive antibiotics (e.g., amoxicillin and cotrimoxazole).

The full extent of antibiotic resistance among developing countries in Africa is unknown. Previous reports suggest wide variation; however, differences in study design and laboratory methods make comparisons difficult (4-7). To standardize surveillance of SP and HI resistance, WHO and CDC have developed a manual that provides details on conducting resistance surveys similar to that described in this report (8).

Because the clinical impact of antibiotic resistance on the treatment of children with pneumonia is not well understood, it is not clear when a national ARI program should change antibiotic recommendations in response to increasing resistance. In CAR, resistance rates were generally low and similar for cotrimoxazole and penicillin/amoxicillin; consequently, MOPHP recommended the use of cotrimoxazole as the first-line treatment for children with pneumonia because of its lower cost, twice-daily dosage, and antimalarial effect. In countries with severely limited budgets for health care and in which resistance to the recommended antibiotic is high, the costs and benefits of replacing a less expensive first-line antibiotic with a more expensive antibiotic to which respiratory pathogens have less resistance must be critically assessed.

Worldwide public health efforts should focus on improving surveillance, developing guidelines for the practical application of surveillance data, advocating policies for the rational use of antibiotics, and ensuring that children in need of antibiotic treatment for pneumonia are treated promptly and correctly. The impact of antibiotic resistance could be minimized by the testing and use of newly developed conjugate vaccines against H. influenzae type b and pneumococcal disease.

References

1. Mastro T, Nomani N, Ishaq Z, et al. Use of nasopharyngeal isolates of Streptococcus pneumoniae and Haemophilus influenzae from children in Pakistan for surveillance for antimicrobial resistance. Pediatr Infect Dis J 1993;12:824-30.

2. World Health Organization. Technical bases for the WHO recommendations on the management of pneumonia in children at first-level facilities. Geneva, Switzerland: World Health Organization, Programme for the Control of Acute Respiratory Infections, 1991; publication no. WHO/ARI/91.20.

3. National Committee for Clinical Laboratory Standards. Performance standards for antimicrobial susceptibility testing. Villanova, Pennsylvania: National Committee for Clinical Laboratory Standards, 1994; document no. M100-S5.

4. Bogaerts J, Lepage P, Taelman H, et al. Antimicrobial susceptibility and serotype distribution of Streptococcus pneumoniae from Rwanda, 1984-1990. J Infect 1993;27:157-68.

5. Klugman K. Pneumococcal resistance to antibiotics. Clin Microbiol Rev 1990;3:171-96.

6. Bijlmer HA, van Alphen L, Greenwood BM, Geelen-van den Broek L, Valkenburg HA, Dankert J. Antibiotic susceptibility of invasive and non-invasive isolates of Haemophilus influenzae from the Gambia, West Africa. J Antimicrob Chemother 1994;34:275-80.

7. Weinberg GA, Spitzer ED, Murray PR, et al. Antimicrobial susceptibility patterns of Haemophilus isolates from children in eleven developing nations. Bull World Health Organ 1990;68:179-84.

8. World Health Organization. Draft version of the manual for the national surveillance of antimicrobial resistance of S. pneumoniae and H. influenzae: epidemiological and microbiological methods. Geneva, Switzerland: World Health Organization, Program for the Control of Acute Respiratory Infections, August 1994.

   
   

+------------------------------------------------------------------- -----+ | Erratum: Vol. 46, No. 3 | | ======================= | | SOURCE: MMWR 46(15);335 DATE: Apr 18, 1997 | |             | | In the article "Antibiotic Resistance Among Nasopharyngeal | | Isolates of Streptococcus pneumoniae and Haemophilus influenzae -- | | Bangui, Central African Republic, 1995," on page 63, a line of text | | was omitted. The second and third sentences in the first full | | paragraph should read, "Among HI isolates, 1.4% were resistant to | | ampicillin, and 12.3% were resistant to cotrimoxazole; no | | B-lactamase was detected in the single ampicillin-resistant | | isolate. The rate of SP resistance to chloramphenicol was 9.2%, and | | no HI isolates were resistant to chloramphenicol." | +------------------------------------------------------------------- -----+

TABLE 1. Number and percentage of antibiotic-resistant * nasopharyngeal isolates of Streptococcus pneumoniae and
Haemophilus influenzae cultured from children aged  2-59 months who were either inpatients or outpatients, by
resistance level -- Bangui, Central African Republic, January-February, 1995
====================================================================================================================
                                               Inpatients                               Outpatients
--------------------------------------------------------------------------------------------------------------------
                                 Intermediate    High       Total          Intermediate   High         Total
                                 ------------   -----   --------------    -------------  -------   -----------------
Organism/Antibiotic                       No.     No.     No.      (%)              No.    No.      No.      (%)
--------------------------------------------------------------------------------------------------------------------
IS. pneumoniae                  n=17 isolates                            n=272 isolates
Penicillin                                  5       0       5   (29.4)               24      0       24   ( 8.8)
Cotrimoxazole +                             4       0       4   (23.5)               15      2       17   ( 6.3)
Tetracycline                                1      10      11   (64.7)               17     98      115   (42.3)
Chloramphenicol                          NA &       3       3   (17.6)             NA &     25       25   ( 9.2)
Erythromycin                                0       0       0       --                0      0        0       --
Clindamycin                                 0       0       0       --                0      0        0       --
Rifampicin                                  0       0       0       --                0      0        0       --
IH. influenzae                   n=8 isolates                             n=73 isolates
Ampicillin @                                0       0       0       --                0      1        1   ( 1.4)
Cotrimoxazole +                             0       0       0       --                2      7        9   (12.3)
Chloramphenicol                             0       0       0       --                0      0        0       --
--------------------------------------------------------------------------------------------------------------------
* Based on standards of the 1994 National Committee for Clinical Laboratory Standards (3).
+ Trimethoprim-sulfamethoxazole.
& Not applicable (chloramphenicol has no intermediate resistance category).
@ Resistance is the same for amoxicillin.
====================================================================================================================

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