Abstract
Two hundred clinical isolates of Haemophilus influenzae were tested for tolerance (MBC/MIC greater than or equal to 32) to ampicillin and cefotaxime by broth dilution tests. Of 200 strains, 9 were tolerant to ampicillin, and 10 were tolerant to cefotaxime. Tolerant organisms were identified in both systemic and nonsystemic infections and among different biotypes and serotypes of H. influenzae. These tolerant isolates were compared with nontolerant isolates by broth dilution and killing curves with log-phase and stationary-phase inocula. Both tolerant and nontolerant bacteria in log phase were killed more rapidly by antibiotics than bacteria in stationary-phase growth. When tested against 11 different beta-lactams, several patterns of tolerance were observed. Six of the ten strains were tolerant to aztreonam, four were tolerant to cefuroxime, three were tolerant to cefamandole, and two were tolerant to cefoxitin. Strain H130 was tolerant to all beta-lactam antibiotics studied. None of the 10 tolerant H. influenzae isolates were tolerant to chloramphenicol, rifampin, tobramycin, ciprofloxacin, enoxacin, and trimethoprim-sulfamethoxazole. Although the clinical significance of tolerance is not determined, this study suggests that the bactericidal activity (MBC) of beta-lactam antibiotics against H. influenzae should be determined in cases of severe infections in which clinical response is slow or unsatisfactory.
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Selected References
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- Barrett F. F., Taber L. H., Morris C. R., Stephenson W. B., Clark D. J., Yow M. D. A 12 year review of the antibiotic management of Hemophilus influenzae meningitis. Comparison of ampicillin and conventional therapy including chloramphenicol. J Pediatr. 1972 Aug;81(2):370–377. doi: 10.1016/s0022-3476(72)80316-0. [DOI] [PubMed] [Google Scholar]
- Bergeron M. G., Claveau S., Simard P. Limited in vitro activity of cefamandole against 100 beta-lactamase- and non-beta-lactamase-producing Haemophilus influenzae strains: comparison of moxalactam, chloramphenicol, and ampicillin. Antimicrob Agents Chemother. 1981 Jan;19(1):101–105. doi: 10.1128/aac.19.1.101. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bradely J. J., Mayhall C. G., Dalton H. P. Incidence and characteristics of antibiotic-tolerant strains of Staphylococcus aureus. Antimicrob Agents Chemother. 1978 Jun;13(6):1052–1057. doi: 10.1128/aac.13.6.1052. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bulger R. R., Washington J. A., 2nd Effect of inoculum size and beta-lactamase production on in vitro activity of new cephalosporins against Haemophilus species. Antimicrob Agents Chemother. 1980 Mar;17(3):393–396. doi: 10.1128/aac.17.3.393. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Denny A. E., Peterson L. R., Gerding D. N., Hall W. H. Serious staphylococcal infections with strains tolerant to bactericidal antibiotics. Arch Intern Med. 1979 Sep;139(9):1026–1031. [PubMed] [Google Scholar]
- Kenny J. F., Isburg C. D., Michaels R. H. Meningitis due to Haemophilus influenzae type b resistant to both ampicillin and chloramphenicol. Pediatrics. 1980 Jul;66(1):14–16. [PubMed] [Google Scholar]
- Kilian M. A taxonomic study of the genus Haemophilus, with the proposal of a new species. J Gen Microbiol. 1976 Mar;93(1):9–62. doi: 10.1099/00221287-93-1-9. [DOI] [PubMed] [Google Scholar]
- Kim K. S., Yoshimori R. N., Imagawa D. T., Anthony B. F. Importance of medium in demonstrating penicillin tolerance by group B streptococci. Antimicrob Agents Chemother. 1979 Aug;16(2):214–216. doi: 10.1128/aac.16.2.214. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Markowitz S. M. Isolation of an ampicillin-resistant, non-beta-lactamase-producing strain of Haemophilus influenzae. Antimicrob Agents Chemother. 1980 Jan;17(1):80–83. doi: 10.1128/aac.17.1.80. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mayhall C. G., Apollo E. Effect of storage and changes in bacterial growth phase and antibiotic concentrations on antimicrobial tolerance in Staphylococcus aureus. Antimicrob Agents Chemother. 1980 Nov;18(5):784–788. doi: 10.1128/aac.18.5.784. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McDonald M., Miles H., Hart D., Sonenberg N. Penicillin tolerance in Streptococcus faecalis. Lancet. 1980 Aug 9;2(8189):321–321. doi: 10.1016/s0140-6736(80)90270-6. [DOI] [PubMed] [Google Scholar]
- Medeiros A. A., O'Brien T. F. Ampicillin-resistant Haemophilus influenzae type B possessing a TEM-type beta-lactamase but little permeability barrier to ampicillin. Lancet. 1975 Mar 29;1(7909):716–719. doi: 10.1016/s0140-6736(75)91630-x. [DOI] [PubMed] [Google Scholar]
- Mendelman P. M., Chaffin D. O., Stull T. L., Rubens C. E., Mack K. D., Smith A. L. Characterization of non-beta-lactamase-mediated ampicillin resistance in Haemophilus influenzae. Antimicrob Agents Chemother. 1984 Aug;26(2):235–244. doi: 10.1128/aac.26.2.235. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nelson J. D. The increasing frequency of beta-lactamase-producing Haemophilus influenzae B. JAMA. 1980 Jul 18;244(3):239–239. [PubMed] [Google Scholar]
- O'Callaghan C. H., Morris A., Kirby S. M., Shingler A. H. Novel method for detection of beta-lactamases by using a chromogenic cephalosporin substrate. Antimicrob Agents Chemother. 1972 Apr;1(4):283–288. doi: 10.1128/aac.1.4.283. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Offit P. A., Campos J. M., Plotkin S. A. Ampicillin-resistant, beta-lactamase-negative haemophilus influenzae type b. Pediatrics. 1982 Feb;69(2):230–232. [PubMed] [Google Scholar]
- Park C. H., Lopez J. S., Cook C. B. Acidometric agar plate method for ampicillin susceptibility testing of Haemophilus influenzae. Antimicrob Agents Chemother. 1978 Feb;13(2):318–320. doi: 10.1128/aac.13.2.318. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Parr T. R., Jr, Bryan L. E. Mechanism of resistance of an ampicillin-resistant, beta-lactamase-negative clinical isolate of Haemophilus influenzae type b to beta-lactam antibiotics. Antimicrob Agents Chemother. 1984 Jun;25(6):747–753. doi: 10.1128/aac.25.6.747. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rubin L. G., Medeiros A. A., Yolken R. H., Moxon E. R. Ampicillin treatment failure of apparently beta-lactamase-negative Haemophilus influenzae type b meningitis due to novel beta-lactamase. Lancet. 1981 Nov 7;2(8254):1008–1010. doi: 10.1016/s0140-6736(81)91214-9. [DOI] [PubMed] [Google Scholar]
- Sabath L. D., Wheeler N., Laverdiere M., Blazevic D., Wilkinson B. J. A new type of penicillin resistance of Staphylococcus aureus. Lancet. 1977 Feb 26;1(8009):443–447. doi: 10.1016/s0140-6736(77)91941-9. [DOI] [PubMed] [Google Scholar]
- Saunders J. R., Sykes R. B. Transfer of a plasmid-specified beta-lactamase gene from Haemophilus influenzae. Antimicrob Agents Chemother. 1977 Feb;11(2):339–344. doi: 10.1128/aac.11.2.339. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Scheifele D. W. Ampicillin-resistant Hemophilus influenzae in Canada: nationwide survey of hospital laboratories. Can Med Assoc J. 1979 Jul 21;121(2):198–202. [PMC free article] [PubMed] [Google Scholar]
- Shanholtzer C. J., Peterson L. R., Mohn M. L., Moody J. A., Gerding D. N. MBCs for Staphylococcus aureus as determined by macrodilution and microdilution techniques. Antimicrob Agents Chemother. 1984 Aug;26(2):214–219. doi: 10.1128/aac.26.2.214. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Simard P., Bergeron M. G. Inoculum size effect on the MIC of cefoperazone, moxalactam, cefotaxime, cefoxitin and cephalothin for 118 strains of Haemophilus influenzae including 'tolerant' micro-organisms. J Antimicrob Chemother. 1982 Nov;10(5):397–402. doi: 10.1093/jac/10.5.397. [DOI] [PubMed] [Google Scholar]
- Taylor P. C., Schoenknecht F. D., Sherris J. C., Linner E. C. Determination of minimum bactericidal concentrations of oxacillin for Staphylococcus aureus: influence and significance of technical factors. Antimicrob Agents Chemother. 1983 Jan;23(1):142–150. doi: 10.1128/aac.23.1.142. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thornsberry C., Kirven L. A. Ampicillin resistance in Haemophilus influenzae as determined by a rapid test for beta-lactamase production. Antimicrob Agents Chemother. 1974 Nov;6(5):653–654. doi: 10.1128/aac.6.5.653. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tomasz A., Albino A., Zanati E. Multiple antibiotic resistance in a bacterium with suppressed autolytic system. Nature. 1970 Jul 11;227(5254):138–140. doi: 10.1038/227138a0. [DOI] [PubMed] [Google Scholar]
- Tomasz A., Waks S. Mechanism of action of penicillin: triggering of the pneumococcal autolytic enzyme by inhibitors of cell wall synthesis. Proc Natl Acad Sci U S A. 1975 Oct;72(10):4162–4166. doi: 10.1073/pnas.72.10.4162. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Venglarcik J. S., 3rd, Blair L. L., Dunkle L. M. pH-dependent oxacillin tolerance of Staphylococcus aureus. Antimicrob Agents Chemother. 1983 Feb;23(2):232–235. doi: 10.1128/aac.23.2.232. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Westerman E. L., Puls J., Medina J. R. Epiglottitis due to ampicillin-tolerant Haemophilus influenzae type b. South Med J. 1984 Mar;77(3):386–387. doi: 10.1097/00007611-198403000-00031. [DOI] [PubMed] [Google Scholar]
- Yourassowsky E., Van Der Linden M. P., Lismont M. J. Growth curves, microscopic morphology, and subcultures of beta-lactamase-positive and -negative Haemophilus influenzae under the influence of ampicillin and cefamandole. Antimicrob Agents Chemother. 1979 Mar;15(3):325–331. doi: 10.1128/aac.15.3.325. [DOI] [PMC free article] [PubMed] [Google Scholar]
