Correspondence
247
isolated from 256 adult cancer patients hospitalized at the Institut Jules Bordet between Edberg, S. C. & Chu, A. (1975). Determining January 1985 and September 1989. The antibiotic levels in the blood. American Journal of sources (with number of isolates) included Medical Technology 41, 99-105. Eron, L. J. Park, C. H., Goldenberg, R. I. & Poretz, sputum (296), bronchial aspirates (17), abscess D. M. (1983). Ceftriaxone therapy of serious (4), and miscellaneous (3). Only one strain was bacterial infections. Journal of Antimicrobial included in the study for each patient, except Chemotherapy 12, 65-78. when there were isolates with different antiJolley, M. E., Stroupe, S. D., Wang, C. H., Panas, biotic susceptibility patterns. H. N., Keegan, C. L., Schmidt, R. L. et al. (1981). Clinical specimens were cultured on chocoFluorescence polarization immunoassay. I. late agar plates which were incubated overMonitoring aminoglycoside antibiotics in serum night at 35°C in 5-7% CO2. Colonies and plasma. Clinical Chemistry 27, 1190-7. Sande, M. A. (1982). Antimicrobial therapy for two suspected to be Haemophilus were then subserious bacterial infections. Enterococcal cultured on to a second chocolate agar plate endocarditis and nosocomial pneumonia. Archives which was incubated under identical conditions. This plate was used to prepare inocula of Internal Medicine 142, 2033-4. Smith, C. R. & Lietman, P. S. (1982). Comparative for all subsequent tests. Organisms were identiclinical trials of aminoglycosides. In The fied as H. influenzae on the basis of colony Aminoglycosides. Microbiology, Clinical Use, andcharacteristics, Gram stain morphology, and Toxicology (Whelton, A. & Neu, H. C , Eds), requirement for factors X and V. /Mactamase pp. 497-509. Marcel Dekker, New York. production was assessed with nitrocefinYogev, R., Shulman, S. T., Chadwick, E. G., Davis, impregnated paper discs (Oxoid). A. T. & Glogowski, W. (1986). Once daily Antibiotic susceptibility to eight antibiotics ceftriaxone for central nervous system infections and other serious pediatric infections. Pediatric (ampicillin, co-amoxiclav [amoxicillin: clavuInfectious Disease 5, 298-303. lanic acid 20:10/Jg], ceftazidime, ceftriaxone, ticarcillin-clavulanic acid (75:10 ug), chloramphenicol, erythromycin, pefloxacin, tetracycline, co-trimoxazole [trimethoprim: sulfamethoxazole 40:200 ug]) was assessed using a Antibiotic resistance in Haemophilus influenzae disc diffusion procedure (NCCLS, 1984). isolated from patients with cancer After incubation of plates for 18 h at 35°C in 5-7% CO2, zones of inhibition were measured Sir, to the nearest millimetre with a caliper and Haemophilus influenzae is recognized as the compared to the NCCLS breakpoints. aetiological agent in a variety of infectious During the study period, a total of 320 diseases in adult population. Invasive clinical isolates of H. influenzae were examHaemophilus infections are caused by encapsu- ined. Among these, 215 were tested with lated type b strains, whereas non-life- erythromycin, 216 with tetracycline, 319 with threatening infections are typically due to non- chloramphenicol, 320 with the combination type b strains. Before 1974 all strains were co-trimoxazole, 316 with ampicillin, 241 with believed to be susceptible to ampicillin. In that pefloxacin, 182 with co-amoxiclav, and 316 year, however, resistance to ampicillin was with ceftazidime. Rates of resistance are shown reported in encapsulated (Tomeh et al., 1974) in Table I. and uncapsulated strains. Ampicillin resistance Ampicillin-resistance was observed in 11 -4% in H. influenzae is most often due to the of strains. These 36 strains were isolated from plasmid-mediated production of TEM 0-lacta- 28 different patients. Among these ampicillinmase (Doern et al., 1988) but alternative mech- resistant strains, 83.3% were susceptible to anisms of resistance include: production of a erythromycin, 50% to tetracycline, 71-4% to /Mactamase different from the TEM-type; chloramphenicol, 77-8% to co-trimoxazole, altered penicillin-binding proteins; and dimin- 100% to pefloxacin, 84-4% to co-amoxiclav, ished permeability (Mendelman et al., 1984; and 85-7% to ceftazidime. Ten strains from Parr & Bryan, 1984; Medeiros, Levesque & eight patients were resistant to ampicillin and Jacoby, 1986; Doern, Daum & Tubert, 1987). chloramphenicol, which represents 3% of We report here the prevalence of anti- isolates tested. Among the five strains resistant microbial resistance in 320 clinical isolates of to co-amoxiclav, four were resistant to H. influenzae isolated in our cancer centre ceftriaxone, ceftazidime, ticarcillin-clavulanic acid and chloramphenicol. All four strains since 1985. A total of 320 H. influenzae strains were were isolated from different patients. References
Downloaded from http://jac.oxfordjournals.org/ at University of Sussex on September 5, 2015
248
Correspondence Table I. Antibiotic resistance of HaemophUus influenzae isolated from 256 cancer patients No. of resistant strains
Antibiotic
(195) (4-6) (3-4) (6-9) (114)
42 10 11 22 36 0 5 5
Erythromycin Tetracycline Chloramphenicol Cotrimoxazole Ampicillin Pefloxacin Coamoxiclav Ceftazidime
(%)
(2-7) (16)
No. of strains % of strains resistant to: tetracycline chloramphenicol cotrimoxazole ampicillin
1985
1986
1987
1988
1989
49
47
56
88
80
0 1-7 1-7 5-3
12-5
NT 50 50 230
2-0 0 40 4-0
21 1-5 10-6
2-1
5-6 11-3 13-9
NT, Not tested. T a b l e II shows that for ampicillin and chloramphenicol, resistance increased markedly from 1985 t o 1989. Co-trimoxazole resistance varied widely from one year to another. Tetracyclines resistance increased in 1988; this antibiotic was n o longer tested from 1989. In other institutions, the percentage of ampicillin-resistant strains ranges from 2 % to 5 5 % depending on the institution and country (Howard, Hince & Williams, 1978; P h i l p o t t - H o w a r d & Williams, 1982; Powell etal., 1987; M a c h k a etal., 1989). Resistance continues to increase for non-type b (Doern etal., 1988) a n d type b strains ( C a m p o s , Garcia-Tornel & Sanfeliu, 1984). In a recent study o n 36 cases of HaemophUus bacteraemia in cancer patients (Fainstein etal., 1989) 6 % of non-typable strains were ampicillin resistant. T h e m o s t c o m m o n mechanism of ampicillin resistance is /Mactamase production. Strains resistant to ampicillin without detectable /Mactamase are u n c o m m o n (0-1%) and are usually uncapsulated (Doern etal., 1987). In the United K i n g d o m , the prevalence of /Mactamase production has not changed between 1981 a n d 1986 ( 1 8 % in type b strains, 6 % in non-capsulated strains). However, the prevalence of ampicillin-resistant, /Mactamase nega-
tive strains increased significantly from 0-4% on 1981 to 1.6% on 1986 (Powell etal, 1987). In Ireland, 10-2% of the strains collected in 1988 were /Mactamase positive and 0-7% were resistant to ampicillin and /Mactamase negative (Howard & Williams, 1989). Such strains are resistant to all /Mactams including c o m binations with a 0-lactamase inhibitor, as documented in four of our strains. Chloramphenicol resistance has been described in clinical isolates of HaemophUus sp. (Doern el al., 1988) and is due to production of chloramphenicol acetyl transferase. In o u r series the rate of chloramphenicol resistance was 3-4%. As shown in Table II, chloramphenicol resistance appeared in 1986 and increased regularly. In the United K i n g d o m survey (Powell et al., 1987), chloramphenicol resistance was extremely unusual (0-2%) in 1977 and increased up to 1 7 % in 1986. There have been occasional reports of strains resistant both to ampicillin and chloramphenicol during the past few years, and these strains generally belonged to serotype b (Heymann, T u r k & Rotimi, 1981; M a c M a h o n etal., 1982; C a m p o s et al., 1984). In the United K i n g d o m survey (Powell et al., 1987), only 13 out of 40 strains resistant to chloramphenicol were also resistant to ampicillin. In this study, chloram-
Downloaded from http://jac.oxfordjournals.org/ at University of Sussex on September 5, 2015
Table II. Evolution of antibiotic resistance in H. influenzae. Other antimicrobial agents tested showed no evolution
Correspondence
X. THOMAS* P. VAN DER AUWERAJ D. DANEAU F. MEUNIER •Current address: Hopilal Edouard Herriol, Pavilion d'Himatologie, Service E2 5, Place d'Arsonval, 69437 Lyon, cedex 03, France. {Corresponding author. Service de Medecine et Laboratoire d'Investigation Clinique H. J. Tagnon, Institut Jules Bordet, Centre des Tumeurs de iUniversite Libre de Bruxelles, Rue Heger-Bordet 1 1000 Brussels. Belgium
References Campos, J., Garcia-Tornel, S. & Sanfeliu, I. (1984). Susceptibility studies of multiple resistant Haemophilus influenzae isolated from pediatric patients and contacts. Antimicrobial Agents and Chemotherapy 25, 706-9. Doern, G. V., Daum, G. S. & Tubert, T. A. (1987). Ampicillin disk diffusion susceptibility testing of Haemophilus influenzae. Journal of Clinical Microbiology 25, 1675-8. Doern, G. V., Jorgensen, J. H., Thornsberry, C , Preston, D. A., Tubert, T., Redding, J. S. etal. (1988). National collaborative study of the prevalence of antimicrobial resistance among clinical isolates of Haemophilus influenzae. Antimicrobial Agents and Chemotherapy 32, 180-5. Fainstein, V., Berkey, P., Elting, L. & Bodey, G. P. (1989). Haemophilus species bacteremia in patients
with cancer. Archives of Internal Medicine 149, 1341-5. Heymann, C. S., Turk, D. C. & Rotimi, V. O. (1981). Multiple antibiotic resistance in Haemophilus influenzae. Lancet i, 553. Howard, A. J., Hince, C. J. & Williams, J. D. (1978). Antibiotic resistance in Streptococcus pneumoniae and Haemophilus influenzae. British Medical Journal i, 1657-60. Howard, A. J. & Williams, H. M. (1989). The prevalence of antibiotic resistance in Haemophilus influenzae in Ireland. Journal of Antimicrobial Chemotherapy 24, 963-71. Machka, K., Braveny, I., Dabernat H., Dornbusch, K., Van Dyck, E., Kayser, F. H. etal. (1988). Distribution and resistance patterns of Haemophilus influenzae: a European cooperative study. European Journal of Clinical Microbiology and Infectious Diseases 7, 14-24. MacMahon, P., Sills, J., Hall, E. & Fitzgerald, T. (1982). Haemophilus influenzae type b resistant to both chloramphenicol and ampicillin in Britain. British Medical Journal 284, 1229. Medeiros, A. A., Levesque, R. & Jacoby, G. A. (1986). An animal source for the ROB-1 /Mactamase of Haemophilus influenzae type b. Antimicrobial Agents and Chemotherapy 29,212-5. Mendelman, P. M., Chaffin, D. O., Stull, T. L., Rubens, C. E., Mack, K. D. & Smith, A. L. (1984). Characterization of non-/?-lactamasemediated ampicillin resistance in Haemophilus influenzae. Antimicrobial Agents and Chemotherapy 26, 235-44. National Committee for Clinical Laboratory Standards (1984). Approved Standard M2-A3: Performance Standards for Antimicrobial Disk Susceptibility Tests, pp. 369-83. National Committee for Clinical Laboratory Standards, Villanova, Pa. Parr, T. R. & Bryan, L. E. (1984). Mechanism of resistance of an ampicillin-resistant, /i-lactamasenegative clinical isolate of Haemophilus influenzae type b to /7-lactam antibiotics. Antimicrobial Agents and Chemotherapy 25, 747-53. Powell, M., Koutsia-Carouzou, C , Voutsinas, D., Seymour, A. & Williams J. D. (1987). Resistance of clinical isolates of Haemophilus influenzae in United Kingdom 1986. British Medical Journal 295, 176-9. Philpott-Howard, J. & Williams, J. D. (1982). Increase in antibiotic resistance in Haemophilus influenzae in the United Kingdom since 1977: report of study group. British Medical Journal 284, 1597-9. Tomeh, M. O., Starr, S. E., MacGowan, J. E., Terry, P. M. & Nahmias, A. J. (1974). Ampicillinresistant Haemophilus influenzae type b infection. Journal of American Medical Association 229, 295-7. Van Dyck, E., Walkiers, D. & Piot, P. (1988). Multiple antimicrobial resistance in Haemophilus influenzae isolates from invasive infections in Belgium (1983-1987). Ada Clinica Belgica 43, 423-8.
Downloaded from http://jac.oxfordjournals.org/ at University of Sussex on September 5, 2015
phenicol resistance occurred in 13/151 /Mactamase positive strains (8-6%) and 27/2149 ampicillin-sensitive strains (1-2%). Among our strains, almost all chloramphenicol-resistant strains were also resistant to ampicillin. Our findings are in contrast with two previously published surveys done in Belgium, with strains isolated almost exclusively from patients without cancer (Machka et al., 1988; Van Dyck, Walkiers & Piot, 1988). In the study of Van Dyck et al. (1988), 35% of invasive strains collected during 1986-87 produced a /Mactamase, of which 22-8% were resistant to chloramphenicol; ampicillin resistance not associated with /Mactamase was not found. In the European survey reported by Machka etal. (1988), 26-7% of strains collected in 1986, mainly from respiratory tract, produced a /Mactamase; 6% were resistant to erythromycin, 11% to chloramphenicol and 18% to tetracycline. In the latter study the authors stated that some isolates were resistant to ampicillin (by MIC) without producing a /Mactamase detectable by the nitrocefin test. Based on the results of one and other surveys, the optimal choice of antibiotic therapy for infections caused by H. influenzae should be based on knowledge of local prevalence of antibiotic resistance.
249
247
isolated from 256 adult cancer patients hospitalized at the Institut Jules Bordet between Edberg, S. C. & Chu, A. (1975). Determining January 1985 and September 1989. The antibiotic levels in the blood. American Journal of sources (with number of isolates) included Medical Technology 41, 99-105. Eron, L. J. Park, C. H., Goldenberg, R. I. & Poretz, sputum (296), bronchial aspirates (17), abscess D. M. (1983). Ceftriaxone therapy of serious (4), and miscellaneous (3). Only one strain was bacterial infections. Journal of Antimicrobial included in the study for each patient, except Chemotherapy 12, 65-78. when there were isolates with different antiJolley, M. E., Stroupe, S. D., Wang, C. H., Panas, biotic susceptibility patterns. H. N., Keegan, C. L., Schmidt, R. L. et al. (1981). Clinical specimens were cultured on chocoFluorescence polarization immunoassay. I. late agar plates which were incubated overMonitoring aminoglycoside antibiotics in serum night at 35°C in 5-7% CO2. Colonies and plasma. Clinical Chemistry 27, 1190-7. Sande, M. A. (1982). Antimicrobial therapy for two suspected to be Haemophilus were then subserious bacterial infections. Enterococcal cultured on to a second chocolate agar plate endocarditis and nosocomial pneumonia. Archives which was incubated under identical conditions. This plate was used to prepare inocula of Internal Medicine 142, 2033-4. Smith, C. R. & Lietman, P. S. (1982). Comparative for all subsequent tests. Organisms were identiclinical trials of aminoglycosides. In The fied as H. influenzae on the basis of colony Aminoglycosides. Microbiology, Clinical Use, andcharacteristics, Gram stain morphology, and Toxicology (Whelton, A. & Neu, H. C , Eds), requirement for factors X and V. /Mactamase pp. 497-509. Marcel Dekker, New York. production was assessed with nitrocefinYogev, R., Shulman, S. T., Chadwick, E. G., Davis, impregnated paper discs (Oxoid). A. T. & Glogowski, W. (1986). Once daily Antibiotic susceptibility to eight antibiotics ceftriaxone for central nervous system infections and other serious pediatric infections. Pediatric (ampicillin, co-amoxiclav [amoxicillin: clavuInfectious Disease 5, 298-303. lanic acid 20:10/Jg], ceftazidime, ceftriaxone, ticarcillin-clavulanic acid (75:10 ug), chloramphenicol, erythromycin, pefloxacin, tetracycline, co-trimoxazole [trimethoprim: sulfamethoxazole 40:200 ug]) was assessed using a Antibiotic resistance in Haemophilus influenzae disc diffusion procedure (NCCLS, 1984). isolated from patients with cancer After incubation of plates for 18 h at 35°C in 5-7% CO2, zones of inhibition were measured Sir, to the nearest millimetre with a caliper and Haemophilus influenzae is recognized as the compared to the NCCLS breakpoints. aetiological agent in a variety of infectious During the study period, a total of 320 diseases in adult population. Invasive clinical isolates of H. influenzae were examHaemophilus infections are caused by encapsu- ined. Among these, 215 were tested with lated type b strains, whereas non-life- erythromycin, 216 with tetracycline, 319 with threatening infections are typically due to non- chloramphenicol, 320 with the combination type b strains. Before 1974 all strains were co-trimoxazole, 316 with ampicillin, 241 with believed to be susceptible to ampicillin. In that pefloxacin, 182 with co-amoxiclav, and 316 year, however, resistance to ampicillin was with ceftazidime. Rates of resistance are shown reported in encapsulated (Tomeh et al., 1974) in Table I. and uncapsulated strains. Ampicillin resistance Ampicillin-resistance was observed in 11 -4% in H. influenzae is most often due to the of strains. These 36 strains were isolated from plasmid-mediated production of TEM 0-lacta- 28 different patients. Among these ampicillinmase (Doern et al., 1988) but alternative mech- resistant strains, 83.3% were susceptible to anisms of resistance include: production of a erythromycin, 50% to tetracycline, 71-4% to /Mactamase different from the TEM-type; chloramphenicol, 77-8% to co-trimoxazole, altered penicillin-binding proteins; and dimin- 100% to pefloxacin, 84-4% to co-amoxiclav, ished permeability (Mendelman et al., 1984; and 85-7% to ceftazidime. Ten strains from Parr & Bryan, 1984; Medeiros, Levesque & eight patients were resistant to ampicillin and Jacoby, 1986; Doern, Daum & Tubert, 1987). chloramphenicol, which represents 3% of We report here the prevalence of anti- isolates tested. Among the five strains resistant microbial resistance in 320 clinical isolates of to co-amoxiclav, four were resistant to H. influenzae isolated in our cancer centre ceftriaxone, ceftazidime, ticarcillin-clavulanic acid and chloramphenicol. All four strains since 1985. A total of 320 H. influenzae strains were were isolated from different patients. References
Downloaded from http://jac.oxfordjournals.org/ at University of Sussex on September 5, 2015
248
Correspondence Table I. Antibiotic resistance of HaemophUus influenzae isolated from 256 cancer patients No. of resistant strains
Antibiotic
(195) (4-6) (3-4) (6-9) (114)
42 10 11 22 36 0 5 5
Erythromycin Tetracycline Chloramphenicol Cotrimoxazole Ampicillin Pefloxacin Coamoxiclav Ceftazidime
(%)
(2-7) (16)
No. of strains % of strains resistant to: tetracycline chloramphenicol cotrimoxazole ampicillin
1985
1986
1987
1988
1989
49
47
56
88
80
0 1-7 1-7 5-3
12-5
NT 50 50 230
2-0 0 40 4-0
21 1-5 10-6
2-1
5-6 11-3 13-9
NT, Not tested. T a b l e II shows that for ampicillin and chloramphenicol, resistance increased markedly from 1985 t o 1989. Co-trimoxazole resistance varied widely from one year to another. Tetracyclines resistance increased in 1988; this antibiotic was n o longer tested from 1989. In other institutions, the percentage of ampicillin-resistant strains ranges from 2 % to 5 5 % depending on the institution and country (Howard, Hince & Williams, 1978; P h i l p o t t - H o w a r d & Williams, 1982; Powell etal., 1987; M a c h k a etal., 1989). Resistance continues to increase for non-type b (Doern etal., 1988) a n d type b strains ( C a m p o s , Garcia-Tornel & Sanfeliu, 1984). In a recent study o n 36 cases of HaemophUus bacteraemia in cancer patients (Fainstein etal., 1989) 6 % of non-typable strains were ampicillin resistant. T h e m o s t c o m m o n mechanism of ampicillin resistance is /Mactamase production. Strains resistant to ampicillin without detectable /Mactamase are u n c o m m o n (0-1%) and are usually uncapsulated (Doern etal., 1987). In the United K i n g d o m , the prevalence of /Mactamase production has not changed between 1981 a n d 1986 ( 1 8 % in type b strains, 6 % in non-capsulated strains). However, the prevalence of ampicillin-resistant, /Mactamase nega-
tive strains increased significantly from 0-4% on 1981 to 1.6% on 1986 (Powell etal, 1987). In Ireland, 10-2% of the strains collected in 1988 were /Mactamase positive and 0-7% were resistant to ampicillin and /Mactamase negative (Howard & Williams, 1989). Such strains are resistant to all /Mactams including c o m binations with a 0-lactamase inhibitor, as documented in four of our strains. Chloramphenicol resistance has been described in clinical isolates of HaemophUus sp. (Doern el al., 1988) and is due to production of chloramphenicol acetyl transferase. In o u r series the rate of chloramphenicol resistance was 3-4%. As shown in Table II, chloramphenicol resistance appeared in 1986 and increased regularly. In the United K i n g d o m survey (Powell et al., 1987), chloramphenicol resistance was extremely unusual (0-2%) in 1977 and increased up to 1 7 % in 1986. There have been occasional reports of strains resistant both to ampicillin and chloramphenicol during the past few years, and these strains generally belonged to serotype b (Heymann, T u r k & Rotimi, 1981; M a c M a h o n etal., 1982; C a m p o s et al., 1984). In the United K i n g d o m survey (Powell et al., 1987), only 13 out of 40 strains resistant to chloramphenicol were also resistant to ampicillin. In this study, chloram-
Downloaded from http://jac.oxfordjournals.org/ at University of Sussex on September 5, 2015
Table II. Evolution of antibiotic resistance in H. influenzae. Other antimicrobial agents tested showed no evolution
Correspondence
X. THOMAS* P. VAN DER AUWERAJ D. DANEAU F. MEUNIER •Current address: Hopilal Edouard Herriol, Pavilion d'Himatologie, Service E2 5, Place d'Arsonval, 69437 Lyon, cedex 03, France. {Corresponding author. Service de Medecine et Laboratoire d'Investigation Clinique H. J. Tagnon, Institut Jules Bordet, Centre des Tumeurs de iUniversite Libre de Bruxelles, Rue Heger-Bordet 1 1000 Brussels. Belgium
References Campos, J., Garcia-Tornel, S. & Sanfeliu, I. (1984). Susceptibility studies of multiple resistant Haemophilus influenzae isolated from pediatric patients and contacts. Antimicrobial Agents and Chemotherapy 25, 706-9. Doern, G. V., Daum, G. S. & Tubert, T. A. (1987). Ampicillin disk diffusion susceptibility testing of Haemophilus influenzae. Journal of Clinical Microbiology 25, 1675-8. Doern, G. V., Jorgensen, J. H., Thornsberry, C , Preston, D. A., Tubert, T., Redding, J. S. etal. (1988). National collaborative study of the prevalence of antimicrobial resistance among clinical isolates of Haemophilus influenzae. Antimicrobial Agents and Chemotherapy 32, 180-5. Fainstein, V., Berkey, P., Elting, L. & Bodey, G. P. (1989). Haemophilus species bacteremia in patients
with cancer. Archives of Internal Medicine 149, 1341-5. Heymann, C. S., Turk, D. C. & Rotimi, V. O. (1981). Multiple antibiotic resistance in Haemophilus influenzae. Lancet i, 553. Howard, A. J., Hince, C. J. & Williams, J. D. (1978). Antibiotic resistance in Streptococcus pneumoniae and Haemophilus influenzae. British Medical Journal i, 1657-60. Howard, A. J. & Williams, H. M. (1989). The prevalence of antibiotic resistance in Haemophilus influenzae in Ireland. Journal of Antimicrobial Chemotherapy 24, 963-71. Machka, K., Braveny, I., Dabernat H., Dornbusch, K., Van Dyck, E., Kayser, F. H. etal. (1988). Distribution and resistance patterns of Haemophilus influenzae: a European cooperative study. European Journal of Clinical Microbiology and Infectious Diseases 7, 14-24. MacMahon, P., Sills, J., Hall, E. & Fitzgerald, T. (1982). Haemophilus influenzae type b resistant to both chloramphenicol and ampicillin in Britain. British Medical Journal 284, 1229. Medeiros, A. A., Levesque, R. & Jacoby, G. A. (1986). An animal source for the ROB-1 /Mactamase of Haemophilus influenzae type b. Antimicrobial Agents and Chemotherapy 29,212-5. Mendelman, P. M., Chaffin, D. O., Stull, T. L., Rubens, C. E., Mack, K. D. & Smith, A. L. (1984). Characterization of non-/?-lactamasemediated ampicillin resistance in Haemophilus influenzae. Antimicrobial Agents and Chemotherapy 26, 235-44. National Committee for Clinical Laboratory Standards (1984). Approved Standard M2-A3: Performance Standards for Antimicrobial Disk Susceptibility Tests, pp. 369-83. National Committee for Clinical Laboratory Standards, Villanova, Pa. Parr, T. R. & Bryan, L. E. (1984). Mechanism of resistance of an ampicillin-resistant, /i-lactamasenegative clinical isolate of Haemophilus influenzae type b to /7-lactam antibiotics. Antimicrobial Agents and Chemotherapy 25, 747-53. Powell, M., Koutsia-Carouzou, C , Voutsinas, D., Seymour, A. & Williams J. D. (1987). Resistance of clinical isolates of Haemophilus influenzae in United Kingdom 1986. British Medical Journal 295, 176-9. Philpott-Howard, J. & Williams, J. D. (1982). Increase in antibiotic resistance in Haemophilus influenzae in the United Kingdom since 1977: report of study group. British Medical Journal 284, 1597-9. Tomeh, M. O., Starr, S. E., MacGowan, J. E., Terry, P. M. & Nahmias, A. J. (1974). Ampicillinresistant Haemophilus influenzae type b infection. Journal of American Medical Association 229, 295-7. Van Dyck, E., Walkiers, D. & Piot, P. (1988). Multiple antimicrobial resistance in Haemophilus influenzae isolates from invasive infections in Belgium (1983-1987). Ada Clinica Belgica 43, 423-8.
Downloaded from http://jac.oxfordjournals.org/ at University of Sussex on September 5, 2015
phenicol resistance occurred in 13/151 /Mactamase positive strains (8-6%) and 27/2149 ampicillin-sensitive strains (1-2%). Among our strains, almost all chloramphenicol-resistant strains were also resistant to ampicillin. Our findings are in contrast with two previously published surveys done in Belgium, with strains isolated almost exclusively from patients without cancer (Machka et al., 1988; Van Dyck, Walkiers & Piot, 1988). In the study of Van Dyck et al. (1988), 35% of invasive strains collected during 1986-87 produced a /Mactamase, of which 22-8% were resistant to chloramphenicol; ampicillin resistance not associated with /Mactamase was not found. In the European survey reported by Machka etal. (1988), 26-7% of strains collected in 1986, mainly from respiratory tract, produced a /Mactamase; 6% were resistant to erythromycin, 11% to chloramphenicol and 18% to tetracycline. In the latter study the authors stated that some isolates were resistant to ampicillin (by MIC) without producing a /Mactamase detectable by the nitrocefin test. Based on the results of one and other surveys, the optimal choice of antibiotic therapy for infections caused by H. influenzae should be based on knowledge of local prevalence of antibiotic resistance.
249
