Abstract
Mezlocillin was used as an initial empiric antibiotic therapy for febrile (> 101 degrees F, ca. 38.33 degrees C) granulocytopenic (< 1,000/microliter) cancer patients. Patients known to be colonized with an organism resistant to 100 micrograms of mezlocillin per mol were excluded. The initial 25 cases (23 patients) received intravenous mezlocillin, 260 mg per kg per day in six divided doses; the mean 1-h-postinfusion serum level was 69 micrograms/ml. Because of the low serum level, the next 25 cases (22 patients) received 450 mg/kg per day, also in six divided doses, resulting in a mean 1-h-postinfusion serum level of 161 micrograms/ml. Both dosage regimens provided similar efficacy. Combined results show that 11 of 21 microbiologically documented infections and 7 of 13 clinically documented infections improved. Instances of bacteremia (number of cases in parentheses) were caused by Pseudomonas aeruginosa (two), Staphylococcus epidermidis (two), Clostridia perfringens (one), and Bacillus species (one); only one case improved. A rise in granulocyte count to > 500/microliters, a serum bactericidal activity of greater than or equal to 1:8 against the infecting pathogen, or both were indicators of a good therapeutic response. Despite exclusion of patients known to be previously colonized with mezlocillin-resistant organisms, 7 of 23 pathogens required a minimal concentration of greater than or equal to 100 micrograms of mezlocillin per ml for inhibition. In addition, surveillance cultures from 18 cases showed resistant organisms colonizing the gingiva, rectum, or both. Side effects of mezlocillin were minimal and included pseudoproteinuria, asymptomatic transient rise in bilirubin, and easily reversible kypokalemia. Mezlocillin, a new semisynthetic penicillin with little toxicity, was found to be inadequate as a single-agent empiric antibiotic therapy for febrile, granulocytopenic cancer patients.
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Selected References
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- Andrassy K., Ritz E., Koderisch J., Salzmann W., Bommer J. Pseudoproteinuria in patients taking penicillin. Lancet. 1978 Jul 15;2(8081):154–154. doi: 10.1016/s0140-6736(78)91537-4. [DOI] [PubMed] [Google Scholar]
- Bauer A. W., Kirby W. M., Sherris J. C., Turck M. Antibiotic susceptibility testing by a standardized single disk method. Am J Clin Pathol. 1966 Apr;45(4):493–496. [PubMed] [Google Scholar]
- Bergan T. Pharmacokinetics of mezlocillin in healthy volunteers. Antimicrob Agents Chemother. 1978 Dec;14(6):801–806. doi: 10.1128/aac.14.6.801. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bloomfield C. D., Kennedy B. J. Cephalothin, carbenicillin, and gentamicin combination therapy for febrile patients with acute non-lymphocytic leukemia. Cancer. 1974 Aug;34(2):431–437. doi: 10.1002/1097-0142(197408)34:2<431::aid-cncr2820340229>3.0.co;2-9. [DOI] [PubMed] [Google Scholar]
- Bodey G. P., Middleman E., Umsawadi T., Rodriguez V. Infections in cancer patients. Results with gentamicin sulfate therapy. Cancer. 1972 Jun;29(6):1697–1701. doi: 10.1002/1097-0142(197206)29:6<1697::aid-cncr2820290638>3.0.co;2-k. [DOI] [PubMed] [Google Scholar]
- Bodey G. P., Pan T. Mezlocillin: in vitro studies of a new broad-spectrum penicillin. Antimicrob Agents Chemother. 1977 Jan;11(1):74–79. doi: 10.1128/aac.11.1.74. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bodey G. P., Rodriguez V., Luce J. K. Carbenicillin therapy of gram-negative bacilli infections. Am J Med Sci. 1969 Jun;257(6):408–414. doi: 10.1097/00000441-196906000-00007. [DOI] [PubMed] [Google Scholar]
- Bodey G. P., Whitecar J. P., Jr, Middleman E., Rodriguez V. Carbenicillin therapy for pseudomonas infections. JAMA. 1971 Oct 4;218(1):62–66. [PubMed] [Google Scholar]
- Fu K. P., Neu H. C. Azlocillin and mezlocillin: new ureido penicillins. Antimicrob Agents Chemother. 1978 Jun;13(6):930–938. doi: 10.1128/aac.13.6.930. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hahn D. M., Schimpff S. C., Young V. M., Fortner C. L., Standiford H. C., Wiernik P. H. Amikacin and cephalothin: empiric regimen for granulocytopenic cancer patients. Antimicrob Agents Chemother. 1977 Nov;12(5):618–624. doi: 10.1128/aac.12.5.618. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Issell B. F., Bodey G. P., Weaver S. Clinical pharmacology of mezlocillin. Antimicrob Agents Chemother. 1978 Feb;13(2):180–183. doi: 10.1128/aac.13.2.180. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Keating M. J., Bodey G. P., Valdivieso M., Rodriguez V. A randomized comparative trial of three aminoglycosides--comparison of continuous infusions of gentamicin, amikacin and sisomicin combined with carbenicillin in the treatment of infections in neutropenic patients with malignancies. Medicine (Baltimore) 1979 Mar;58(2):159–170. doi: 10.1097/00005792-197903000-00004. [DOI] [PubMed] [Google Scholar]
- Klastersky J., Cappel R., Daneau D. Clinical significance of in vitro synergism between antibiotics in gram-negative infections. Antimicrob Agents Chemother. 1972 Dec;2(6):470–475. doi: 10.1128/aac.2.6.470. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Klastersky J., Hensgens C., Debusscher L. Empiric therapy for cancer patients: comparative study of ticarcillin-tobramycin, ticarcillin-cephalothin, and cephalothin-tobramycin. Antimicrob Agents Chemother. 1975 May;7(5):640–645. doi: 10.1128/aac.7.5.640. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Love L. J., Schimpff S. C., Hahn D. M., Young V. M., Standiford H. C., Bender J. F., Fortner C. L., Wiernik P. H. Randomized trial of empiric antibiotic therapy with ticarcillin in combination with gentamicin, amikacin or netilmicin in febrile patients with granulocytopenia and cancer. Am J Med. 1979 Apr;66(4):603–610. doi: 10.1016/0002-9343(79)91170-7. [DOI] [PubMed] [Google Scholar]
- Love L. J., Schimpff S. C., Schiffer C. A., Wiernik P. H. Improved prognosis for granulocytopenic patients with gram-negative bacteremia. Am J Med. 1980 May;68(5):643–648. doi: 10.1016/0002-9343(80)90243-0. [DOI] [PubMed] [Google Scholar]
- MacLowry J. D., Jaqua M. J., Selepak S. T. Detailed methodology and implementation of a semiautomated serial dilution microtechnique for antimicrobial susceptibility testing. Appl Microbiol. 1970 Jul;20(1):46–53. doi: 10.1128/am.20.1.46-53.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Murillo J., Standiford H. C., Schimpff S. C., Tatem B. A. Comparison of serum bactericidal activity among three antimicrobial combinations. Antimicrob Agents Chemother. 1978 Jun;13(6):992–996. doi: 10.1128/aac.13.6.992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pancoast S. J., Jahre J. A., Neu H. C. Mezlocillin in the therapy of serious infections. Am J Med. 1979 Nov;67(5):747–752. doi: 10.1016/0002-9343(79)90729-0. [DOI] [PubMed] [Google Scholar]
- Rodriguez V., Bodey G. P., Horikoshi N., Inagaki J., McCredie K. B. Ticarcillin therapy of infections. Antimicrob Agents Chemother. 1973 Oct;4(4):427–431. doi: 10.1128/aac.4.4.427. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schiffer C. A. Principles of granulocyte transfusion therapy. Med Clin North Am. 1977 Sep;61(5):1119–1131. doi: 10.1016/s0025-7125(16)31285-8. [DOI] [PubMed] [Google Scholar]
- Schimpff S. C., Greene W. H., Young V. M., Wiernik P. H. Significance of Pseudomonas aeruginosa in the patient with leukemia or lymphoma. J Infect Dis. 1974 Nov;130 (Suppl)(0):S24–S31. doi: 10.1093/infdis/130.supplement.s24. [DOI] [PubMed] [Google Scholar]
- Schimpff S. C., Landesman S., Hahn D. M., Standiford H. C., Fortner C. L., Young V. M., Wiernik P. H. Ticarcillin in combination with cephalothin or gentamicin as empiric antibiotic therapy in granulocytopenic cancer patients. Antimicrob Agents Chemother. 1976 Nov;10(5):837–844. doi: 10.1128/aac.10.5.837. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schimpff S., Satterlee W., Young V. M., Serpick A. Empiric therapy with carbenicillin and gentamicin for febrile patients with cancer and granulocytopenia. N Engl J Med. 1971 May 13;284(19):1061–1065. doi: 10.1056/NEJM197105132841904. [DOI] [PubMed] [Google Scholar]
- Smith C. R., Baughman K. L., Edwards C. Q., Rogers J. F., Lietman P. S. Controlled comparison of amikacin and gentamicin. N Engl J Med. 1977 Feb 17;296(7):349–353. doi: 10.1056/NEJM197702172960701. [DOI] [PubMed] [Google Scholar]
- Valdivieso M., Horikoshi N., Rodriguez V., Bodey G. P. Therapeutic trials with tobramycin. Am J Med Sci. 1974 Sep;268(3):149–156. doi: 10.1097/00000441-197409000-00003. [DOI] [PubMed] [Google Scholar]
