Pharmacokinetics and Bacteriologic Efficacy of Moxalactam, Cefotaxime, Cefoperazone, and Rocephin in Experimental Bacterial Meningitis

Schaad, Urs B.; McCracken, George H.; Loock, Christine; Thomas, Marion L.

doi:10.1093/infdis/143.2.156

Cited by 149 publications

(72 citation statements)

References 19 publications

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“…Bacteria grow slowly in CSF when compared with broth (42)2, which may interfere with the action of certain antibiotics, such as the beta lactams, maximally effective during rapid bacterial growth. In addition, the normal clearance mechanism of the CSF is operative early during experimental meningitis (43), but resistance to CSF outflow increases during experimental meningitis in rabbits (44) (25,26). These studies were of short duration; the experiments in this paper are confirmatory and extend these observations to long term (5 d) therapy and ultimate outcome (e.g., cure).…”

Section: Discussionsupporting

confidence: 59%

“…The results strongly support the conclusion that when CSF antibiotic levels exceeded the MBC for the test strain, the results of therapy were significantly better by all parameters than the results achieved with regimens that did not attain CSF antibiotic concentrations above this level. The need for bactericidal antibiotics for optimal therapy of bacterial meningitis is suggested by several lines of evidence: (a) the disease represents an infection in an area of impaired host resistance (7-9, 13, 24), and may, like bacterial endocarditis and bacteremia in the neutropenic host (15,16), require bactericidal antibiotics for cure; and (b) most studies of experimental meningitis in animals suggest that CSF antibiotic concentrations must exceed the MBC of the test strain by severalfold to achieve rapid bacterial killing in vivo (17)(18)(19)(25)(26)(27)(28).…”

Section: Discussionmentioning

confidence: 99%

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Bactericidal versus Bacteriostatic Antibiotic Therapy of Experimental Pneumococcal Meningitis in Rabbits

Scheld¹,

Sande²

1983

J. Clin. Invest.

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A B S T R A C T A rabbit model of pneumococcal meningitis was used to examine the importance of bactericidal vs. bacteriostatic antimicrobial agents in the therapy of meningitis. 112 animals were infected with one of two strains of type III Streptococcus pneumoniae. Both strains were exquisitely sensitive to ampicillin, minimum inhibitory concentration (MIC)/ minimum bactericidal concentration (MBC) <0.125 ug/ml. The activity of chloramphenicol against the two strains varied: strain1-MIC 2 ug/ml, MBC 16 /Ag/ml; strain2-MIC 1 ,g/ml, MBC 2 ,g/ml. Animals were treated with either ampicillin or chloramphenicol in dosages that achieved a peak bactericidal effect in cerebrospinal fluid (CSF) for ampicillin against both strains. Two different dosages were used for chloramphenicol. The first dosage achieved a peak CSF concentration of 4.4±1.1 gg/ml that produced a bacteriostatic effect against strainI and bactericidal effect against strain2. The second dosage achieved a bactericidal effect against both strains (mean peak CSF concentration 30.0 Ag/ml). All

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Section: Discussionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Bactericidal versus Bacteriostatic Antibiotic Therapy of Experimental Pneumococcal Meningitis in Rabbits

Scheld¹,

Sande²

1983

J. Clin. Invest.

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“…This is particularly applicable to GBS meningitis, the most common clinical GBS syndrome. Ceftizoxime resembles other new ,B-lactams in this regard, such as moxalactam, cefoperazone, rocephin, and cefotaxime (11).…”

mentioning

confidence: 96%

“…There are no other reported series of the in vitro bactericidal efficacy of the newer cephalosporin agents against large numbers of GBS strains as is currently presented. However, ceftizoxime appears to have MBCs against nontolerant GBS comparable to those of cefotaxime, cefoperazone, and rocephin and superior to that of moxalactam (11). In a study of only nine GBS clinical isolates, Shaad et al (11) reported an MBC of cefoperazone and rocephin for 90%o of isolates of 0.25 ,ug/ml, whereas for cefotaxime it was 0.12 ,ug/ ml.…”

mentioning

confidence: 98%

“…However, ceftizoxime appears to have MBCs against nontolerant GBS comparable to those of cefotaxime, cefoperazone, and rocephin and superior to that of moxalactam (11). In a study of only nine GBS clinical isolates, Shaad et al (11) reported an MBC of cefoperazone and rocephin for 90%o of isolates of 0.25 ,ug/ml, whereas for cefotaxime it was 0.12 ,ug/ ml. This compares favorably to the ceftizoxime MBC for 90%o of isolates of 0.48 /ml for the 92 nontolerant GBS strains in the present study.…”

mentioning

confidence: 98%

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Comparative in vitro bactericidal activity of cefonicid, ceftizoxime, and penicillin against group B streptococci

Bayer¹,

Morrison²,

Kim³

1982

Antimicrob Agents Chemother

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The minimal inhibitory and bactericidal concentrations for 108 group B streptococcal strains were determined for two new cephalosporins, cefonicid and ceftizoxime, and compared to those of penicillin G. Penicillin G was the most active inhibitory and bactericidal agent. Ceftizoxime was a significantly more active inhibitory and bactericidal agent than cefonicid (P < 0.0005, P < 0.025, respectively).Penicillin G and ampicillin have remained the drugs of first choice in infections due to group B streptococci (GBS) because of low minimal inhibitory and bactericidal concentrations (MICs, MBCs) reported in most studies (3). However, investigators have been prompted to examine non-penicillin regimens for in vitro inhibitory and bactericidal efficacy for several reasons: (i) high morbidity and mortality rates of GBS infections, especially in neonates (2); (ii) increasing reports of relapse or recurrence of GBS infection despite penicillin therapy (4); (iii) reports of GBS strains relatively resistant or tolerant to the killing action of penicillin (1,8); and (iv) limited data on alternative (non-penicillin) bactericidal agents for GBS, especially for patients who are allergic to penicillin or who develop penicillin end-organ toxicity (e.g., nephropathy).We have examined the in vitro inhibitory and bactericidal activity of two new cephalosporins, cefonicid (first generation) and ceftizoxime (third generation), against 108 blood and spinal fluid GBS isolates and compared these activities with those of penicillin G.The bacterial strains used in this study were identified as GBS according to Lancefield's criteria (9). The GBS were isolates of the Harbor-UCLA Medical Center, the University of Minnesota Hospitals, the University of Alabama Medical Center, and the Charity Hospital of New Orleans, Louisiana, between 1976 and 1980. There were no duplicate isolates from the same patient. Aliquots of logarithmic-phase cultures of each strain in Mueller-Hinton broth (Difco Laboratories, Detroit, Mich.) were stored at -70°C until susceptibility testing was performed.A late-logarithmic-phase culture of each GBS isolate was prepared in Mueller-Hinton broth as previously described (7,8) at -2 x 105 colonyforming units per ml. Potassium penicillin G (Bristol Laboratories, Syracuse, N.Y.), and cefonicid and ceftizoxime (Smith, Kline & French Laboratories, Philadelphia, Pa.) were reconstituted to concentrations of 10,000 ,ug/ml and stored in aliquots at -70°C until the susceptibility testing was performed (within 4 weeks of freezing).MICs and MBCs of the 108 GBS isolates to penicillin, cefonicid, and ceftizoxime were determined in duplicate by the microtiter brothdilution technique; a GBS control strain with previously determined MICs and MBCs was included with each run as a check on reproducibility. Each antibiotic agent to be tested was thawed immediately before use, and serial twofold dilutions were made in Mueller-Hinton broth in the microtiter wells. For cefonicid and ceftizoxime, the final drug concentration range in the wells wa...

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Bacterial Infections in Infants 60 Days and Younger

Sadow

Derr²,

Teach³

1999

Arch Pediatr Adolesc Med

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To establish what might be more optimal initial antibiotic therapy for suspected invasive bacterial infections in infants 60 days or younger who are evaluated in the emergency department (ED). Setting: Urban university-affiliated pediatric referral center with an average yearly ED census of 52 000 visits during the study period. Design and Methods: We assembled a retrospective case series of all positive blood, urine, and cerebrospinal fluid cultures in children 60 days or younger from January 1, 1994, through December 31, 1997, obtained from both inpatients and patients initially evaluated in the ED. From this case series we determined the frequency of bacterial pathogens responsible for such infections in this age group. Pathogens were defined as group B streptococcus, various enteric gram-negative rods (GNRs), Listeria monocytogenes, enterococcus, Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae type B, and Staphylococcus aureus. A subgroup analysis was performed to determine resistance patterns among the GNRs isolated from patients evaluated in the ED. Results: A total of 367 pathogens were isolated: 187 (51.0%) in the neonatal intensive care unit, 153 (41.7%) in the ED, 20 (5.4%) in the inpatient wards, and 7 (1.9%) in the pediatric intensive care unit. Of the 121 patho

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Pharmacokinetics and Bacteriologic Efficacy of Moxalactam, Cefotaxime, Cefoperazone, and Rocephin in Experimental Bacterial Meningitis

Cited by 149 publications

References 19 publications

Bactericidal versus Bacteriostatic Antibiotic Therapy of Experimental Pneumococcal Meningitis in Rabbits

Bactericidal versus Bacteriostatic Antibiotic Therapy of Experimental Pneumococcal Meningitis in Rabbits

Comparative in vitro bactericidal activity of cefonicid, ceftizoxime, and penicillin against group B streptococci

Bacterial Infections in Infants 60 Days and Younger

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