REVIEW

Cephalothin and Cephaloridine Therapy for Bacterial Meningitis An Evaluation LARRY S. FISHER, M.D., ANTHONY W. CHOW, M.D., F.R.C.P.(C), and LUCIEN B. GUZE, M.D., F.A.C.P., Torrance and Los Angeles,

The efficacy of cephalothin and cephaloridine in the treatment of bacterial meningitis was evaluated from a review of 106 cases reported in the literature. Fifty-nine percent of 34 patients treated with intravenous cephalothin responded suboptimally; those receiving daily doses of 12 g or more fared significantly better (P < 0.025). In contrast, 7 4 % of 72 patients treated with cephaloridine responded favorably; those who received concomitant intrathecal cephaloridine responded significantly better (P < 0.005). These findings indicate that cephalosporin therapy for bacterial meningitis, without concomitant intrathecal medication, is unreliable and that this is probably due to inadequate penetration of the antibiotics into cerebrospinal fluid. In penicillin-allergic patients with pneumococcal, meningococcal, and hemophilus meningitis, chloramphenicol is the agent of choice. For staphylococcal meningitis, intravenous cephalothin at doses of 12 g/day with additional intrathecal cephaloridine at doses of 12.5 to 50 mg/day should be administered concomitantly.

CEPHALOTHIN AND CEPHALORIDINE have both been used

extensively for various bacterial infections since 1963 (1-6). However, the efficacy of these cephalosporins in the treatment of bacterial meningitis has not been clearly established. Consequently, available data of 106 patients with bacterial meningitis treated with either cephalothin or cephaloridine were reviewed from the English literature in order to elucidate the efficacy of these antibiotics and to provide guidelines for choice of alternate agents in patients allergic to penicillin. Literature Review

Pertinent data on 106 patients with bacterial meningitis due to various organisms, treated with either cephalothin or cephaloridine, have been reviewed and are summarized in Table 1. In almost all cases, the rationale for cephalosporin • From the Departments of Medicine, Harbor General Hospital, Torrance, California, and UCLA School of Medicine, Los Angeles, California, and the Research and Medical Services, Veterans Administration Hospital (Wadsworth), Los Angeles, California.

THOMAS T. YOSHIKAWA, M.D., California

therapy was either suspected or documented penicillin allergy. Thirty-four patients were treated with cephalothin parenterally, and none underwent intrathecal therapy (Table 2 ) . Only 14 patients ( 4 1 % ) , responded favorably. In 20 patients ( 5 9 % ) , cephalothin therapy was unsuccessful. Thirteen patients either developed meningitis or continued to have positive cerebrospinal fluid (CSF) cultures, and 7 patients clinically deteriorated while receiving cephalothin therapy. Thirteen of these 20 patients had available data indicating that other antibiotics were administered because of suboptimal clinical response. Six patients died, 2 of whom succumbed while on another antibiotic in addition to cephalothin. Among 13 patients who received cephalothin at daily doses of 12 g or more, only 4 patients ( 3 1 % ) did not respond. In contrast, 13 of 16 patients (81%) who received less than 12 g daily of cephalothin responded suboptimally (P < 0.025, x2 analysis). The daily dose of cephalothin was not specified in the remaining 5 patients. Seventy-two patients were treated with cephaloridine; in 56 patients, intrathecal cephaloridine was also administered (Table 3). Fifty-three patients (74% ) responded favorably; of these, 47 were also given intrathecal cephaloridine. In 19 patients, response to cephaloridine therapy was suboptimal. At least 5 patients had positive CSF cultures during therapy. Fifteen patients died ( 2 1 % ) , 1 of whom succumbed while on another antibiotic in addition to cephaloridine. Among 56 patients who received additional cephaloridine by intrathecal administration, only 9 patients ( 1 6 % ) did not respond. In contrast, 10 of 16 patients ( 6 3 % ) who did not receive intrathecal cephaloridine responded suboptimally (P < 0.005, x 2 analysis). Discussion

Although both cephalothin and cephaloridine have been used successfully against a variety of bacterial infections, their efficacy against meningitis has not been clearly established. Indeed, our review indicates that the response to cephalorosporin therapy in 106 patients with bacterial

Annals of Internal Medicine 82:689-693, 1975

Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/19497/ by a University of California San Diego User on 06/26/2017

689

Table 3L. Bacterial Meningit is Treated with (Cephalothin or Cephaloricline* Case

Organisms

MIC

ng/ml Cephalothin 1 Meningococcus

Sensitive to 30-/xg disc Sensitive to 30-/-ig disc 0.4 0.4 0.2 0.4

2

Meningococcus

3 4 5 6 7 8 9 10 11 12 13 14 15

Meningococcus Meningococcus Meningococcus Meningococcus Meningococcus Meningococcus Meningococcus Meningococcus Meningococcus Meningococcus Meningococcus Meningococcus Meningococcus

16 17 18

Meningococcus Meningococcus Pneumococcus

19

Pneumococcus

20

Pneumococcus

21 22 23 24 25 26 27

Pneumococcus Pneumococcus Pneumococcus Staphylococcus Staphylococcus Staphylococcus Hemophilus influenzae

28 29

32

H. influenzae Listeria