Antibiotic Prophylaxis of Carriers of Sulfadiazine-Resistant Meningococci

Dowd, John M.; Blink, Donald; Miller, Charles H.; Frank, Paul F.; Pierce, Willard E.

doi:10.1093/infdis/116.4.473

Cited by 32 publications

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“…In the doses we used, the percentage of subjects culture negative 2 weeks after drug administration was no higher than that obtained with beta-lactam antibiotics studied in the past (2,3,8 …”

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confidence: 67%

Evaluation of Sch 29,482 in the eradication of Neisseria meningitidis from nasopharyngeal carriers

Pugsley¹,

Dworzack²,

Sanders³

et al. 1984

Antimicrob Agents Chemother

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Fifty-eight chronic carriers of Neisseria meningitidis were given 250 mg of Sch 29,482 or placebo orally every 6 h for 4 days. Although 22 of 29 subjects taking Sch 29,482 became culture negative while taking the drug, only five were culture negative 2 weeks posttherapy. There were no significant adverse reactions.Neisseria meningitidis remains one of the leading causes of acute bacterial meningitis. Chemoprophylaxis of close contacts of patients can halt spread of the disease (13). Currently, rifampin and minocycline are the drugs of choice for this purpose (1). However, both agents have real and potential drawbacks. Minocycline use is associated with a high incidence of tinnitus and vertigo (9). The use of rifampin in closed populations has been followed by the isolation of rifampin-resistant strains (11, 14 >0.125 p.g/ml. The minimum concentration inhibiting 90% of strains was 0.036 ,xg/ml.After approval by the Creighton University Human Research Committee, we screened 555 healthy young men (the majority of which were college students) for the presence of nasopharyngeal N. meningitidis during March 1982 and found 139 (25%) to be colonized. Based on two consecutive positive cultures at weekly intervals, 81 of the 139 subjects (58%) were designated chronic carriers, and 59 of these men were entered into the study. Before entry, informed consent was obtained, a medical history was obtained from each subject, and a physical examination was performed. Laboratory screening tests (complete blood count, prothrombin time, urinalysis, urea nitrogen, creatinine, total and direct bilirubin, aspartate aminotransferase, and alkaline phosphatase) were also collected. No subject had evidence of penicillin allergy, antibiotic use within 3 weeks of the first culture, serious underlying disease, or concomitant infection.In a double-blinded fashion, subjects were assigned to receive identical capsules containing either 250 mg of Sch 29,482 or placebo based on a random number table. Subjects were instructed to take one capsule every 6 h for 4 days (30 min before meals). The use of concomitant medication was limited to analgesics, decongestants, and antihistamines.Each subject was questioned daily with regard to adverse reactions, and a daily nasopharyngeal culture was obtained.Cultures were also taken 7 and 14 days after drug administration was completed. Each subject underwent a repeat physi-* Corresponding author. cal examination and laboratory tests 7 days after the conclusion of drug administration. Compliance was judged by the return of all capsules not taken and empty drug containers.Nasopharyngeal swabs were streaked onto modified Thayer-Martin agar and were incubated at 37°C in 10% CO2 in air for 48 h. Colonies resembling N. meningitidis were identified by positive oxidase reactions and by the fermentation of glucose and maltose in the absence of sucrose and lactose fermentation. Cultures were considered positive if any N. meningitidis colonies were identified. The MICs of rifampin and Sch 29,482 were determined on pr...

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confidence: 67%

Evaluation of Sch 29,482 in the eradication of Neisseria meningitidis from nasopharyngeal carriers

Pugsley¹,

Dworzack²,

Sanders³

et al. 1984

Antimicrob Agents Chemother

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“…6). Penetration into saliva and tears was either immeasurably slight or meager, despite the administration of 250 mg every 6 h. Oxytetracycline was not effective in the treatment of carriers of N. meningitidis (17). It is probable that tetracycline would be equally ineffective.…”

Section: Discussionmentioning

confidence: 98%

“…Because these congeners differ in lipophilicity, they and tetracycline (TC) penicillin G (12, 19, 20, 30, 58). However, chemoprophylaxis is another matter, for the penicillins do not affect the carrier state (2,17,42,51). Field trials with several other antimicrobics, also active against meningococci by testing in vitro, have shown either-no useful effect (oxytetracycline, erythromycin, nalidixic acid, trimethoprim, ethoxzolamide, doxycycline, cephalexin, and coumermycin [2,11,13,16,17,42,45,51]), or reduction in carriers (rifampin [3,10,14,19,26,57] and minocycline [15,26]).…”

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confidence: 99%

“…Yet, in the field, oxytetracycline (17) and doxycycline (16) failed to influence the carrier state, whereas minocycline reduced carriers by 95 to 84% (15,26). To rationalize these findings and relate them to the physicochemical characteristics of the tetracyclines (9,35,54), the entry of oxytetracycline, tetracycline, minocycline, and doxycycline into saliva and tears was studied in normal volunteers.…”

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confidence: 99%

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Entry of Four Tetracyclines into Saliva and Tears

Hoeprich

Warshauer

1974

Antimicrob Agents Chemother

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Although meningococci are susceptible to the tetracyclines by testing in vitro, oxytetracycline (OC) and doxycycline (DC) have failed to eliminate carriage, whereas minocycline (MC) has been effective. Because these congeners differ in lipophilicity, they and tetracycline (TC) penicillin G (12, 19, 20, 30, 58). However, chemoprophylaxis is another matter, for the penicillins do not affect the carrier state (2,17,42,51). Field trials with several other antimicrobics, also active against meningococci by testing in vitro, have shown either-no useful effect (oxytetracycline, erythromycin, nalidixic acid, trimethoprim, ethoxzolamide, doxycycline, cephalexin, and coumermycin [2,11,13,16,17,42,45,51]), or reduction in carriers (rifampin [3,10,14,19,26,57] and minocycline [15,26]).The congeners of tetracycline available for therapy are active in vitro against meningococci (12,15,19,20,26). Yet, in the field, oxytetracycline (17) and doxycycline (16) failed to influence the carrier state, whereas minocycline reduced carriers by 95 to 84% (15, 26). To rationalize these findings and relate them to the physicochemical characteristics of the tetracyclines (9,35,54), the entry of oxytetracycline, tetracycline, minocycline, and doxycycline into saliva and tears was studied in normal volunteers.The rationale for relating penetration of antimicrobic into saliva and tears to antimeningococcic chemoprophylactic efficacy has been presented elsewhere (28). Briefly, it is impractical to measure drug content in the mucous secretions that bathe the noninflamed nasopharyngeal site of carriage of N. meningitidis. Although saliva does not ordinarily wet the nasopharynx, tears pass into the nasopharynx as the normal route of drainage from the conjunctival sac. Moreover, agents known to be prophylactic-sulfapyrimidines (32, 49, 55) and rifampin (3, 10, 14, 19, 26, 57)

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“…Naval Training Center in San Diego, several authors have reported the increasing prevalence of sulphadiazine-resistant group B and group C meningococci in the military and civil population (Bories, Faucon, Audiffren & Bonzom, 1964;Bories, Faucon, Oddou & Audiffren, 1965;Leedom et at. 1965;Bristow, van Peenen & Volk, 1965;Eickhoff & Finland 1965;Feldman, 1966;Farrell & Dahl, 1966;Dowd et al 1966;Sanders, 1967;and others). In fact, group B meningococci were reported to be less uniformly inhibited by sulphonamides than other meningococcal types by Branham, as early as 1940 and 1953 (cited by Leedom et al 1965).…”

Section: Introductionmentioning

confidence: 98%

Sulphadiazine-resistant group A meningococci isolated during the 1968 meningitis epidemic in Greece

Vassiliadis¹,

Kanellakis²,

Papadakis³

1969

J. Hyg.

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SUMMARYDuring the 1968 epidemic of meningococcal meningitis in Greece, 90% of the meningococci recovered from the spinal fluid of patients belonged to serological group A. In one army barracks and in one Naval Training Centre, where cases occurred, a rate of 52% and 38·9% respectively of healthy nasopharyngeal carriers of group A meningococci was found, despite repeated courses of sulpha-prophylaxis given to all the population of these military establishments shortly before the swabs were taken.The susceptibility to sulphadiazine of 64 group A meningococci isolated from patients in different regions of the country and from healthy carriers was tested in vitro. It was found that only one strain was sensitive to a concentration of 0·1 mg./100 ml. of sulphadiazine and another to 1 mg./100 ml. For the remaining strains, the minimal inhibitory concentrations of sulphadiazine ranged from 5 mg./100 ml. to more than 20 mg./100 ml.Thirty-six strains of group B meningococci were isolated from 34 healthy carriers and from two patients. Some of these strains were resistant to sulphadiazine. Only three strains of group C meningococci were isolated from healthy nasopharyngeal carriers in one army barracks.We wish to express our thanks to Dr R. Faucon, Director of the International Reference Centre for meningococci, for the valuable help he gave to us during our investigation, as well as for the supply of the group-specific agglutinating antimeningococcal sera.

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Antibiotic Prophylaxis of Carriers of Sulfadiazine-Resistant Meningococci

Cited by 32 publications

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Evaluation of Sch 29,482 in the eradication of Neisseria meningitidis from nasopharyngeal carriers

Evaluation of Sch 29,482 in the eradication of Neisseria meningitidis from nasopharyngeal carriers

Entry of Four Tetracyclines into Saliva and Tears

Sulphadiazine-resistant group A meningococci isolated during the 1968 meningitis epidemic in Greece

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