Ceftazidime therapy in patients with cystic fibrosis and multiply-drug-resistant pseudomonas

Blumer, Jeffrey L.; Stern, Robert C.; Klinger, Jeffrey D.; Yamashita, Toyoko S.; Meyers, Carolyn; Blum, Adam; Reed, Michael D.

doi:10.1016/0002-9343(85)90259-1

Cited by 38 publications

(22 citation statements)

References 19 publications

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“…In contrast, ceftazidime monotherapy had no effect on sputum colony counts for any P. cepacia isolate. The absence of an effect on P. cepacia sputum isolates was observed despite the potent activity ceftazidime demonstrated in vitro against this microorganism (Table 2) relative to achievable ceftazidime concentrations in sputum reported previously (2,11). Moreover, a dramatic effect on sputum P. aeruginosa colonization was observed, even though ceftazidime displayed less potency and variable in vitro activity against these isolates.…”

Section: Resultsmentioning

confidence: 73%

“…Pharmacologic evaluations of ceftazidime in these patients have demonstrated altered biodisposition characteristics (8) similar to those observed for other antimicrobial agents in patients with CF (9,12,16). Our previous experience assessing the sputum penetration characteristics of ceftazidime in patients with CF revealed sputum drug concentrations which equalled or only marginally exceeded the MIC for pseudomonal isolates (2). Despite these potential pharmacologic limitations, numerous studies have documented the clinical efficacy of ceftazidime monotherapy in the treatment of acute pulmonary exacerbations experienced by patients with CF (2,3,6,11).…”

mentioning

confidence: 70%

“…Our previous experience assessing the sputum penetration characteristics of ceftazidime in patients with CF revealed sputum drug concentrations which equalled or only marginally exceeded the MIC for pseudomonal isolates (2). Despite these potential pharmacologic limitations, numerous studies have documented the clinical efficacy of ceftazidime monotherapy in the treatment of acute pulmonary exacerbations experienced by patients with CF (2,3,6,11). These data combined suggest that an increased total daily dose of ceftazidime might improve bacteriologic or patient clinical response.…”

mentioning

confidence: 99%

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Randomized double-blind evaluation of ceftazidime dose ranging in hospitalized patients with cystic fibrosis

Reed¹,

Stern²,

O'Brien³

et al. 1987

Antimicrob Agents Chemother

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Eighty-five patients with cystic fibrosis who were experiencing an acute infectious exacerbation of their disease were randomized in double-blind fashion to receive either 50 or 75 mg of ceftazidime per kg (body weight) per dose administered intravenously every 8 h for 14 days. Three patients were dropped from the study within 4 days of enrollment for reasons unrelated to drug administration. The total daily dose of ceftazidime administered was restricted by protocol design and was independent of the body weight of the patient. Thus, for datum analysis, patients were separated into three ceftazidime dosage groups (denoted as range of milligrams per kilogram per dose): group 1, 22 to 44.5; group 2, 46.3 to 56.6; and group 3, 66.7 to 80.6. Ceftazidime monotherapy had no effect on sputum colony counts for any Pseudomonas cepacia isolate. In contrast, a substantial reduction in Pseudomonas aeruginosa sputum colony counts was observed, and from 19 to 31% of isolates were suppressed _i10 CFU/mi after 14 days of therapy. Bacterial resistance in vitro was not observed, although a trend for increasing ceftazidime MICs was observed for group 1 patients (P < 0.05). Overall, clinical response appeared independent of drug dose, and no relationship could be identified between the reduction in P. aeruginosa sputum colony counts and clinical outcome. Adverse effects of ceftazidime were mild and transient, necessitating drug discontinuation in one patient. These data suggest that the clinical response to ceftazidime in patients with cystic fibrosis may be maximal with 50 mg/kg per dose (150 mg/kg per day) up to a total daily dose of 6 g.Ceftazidime, an aminothiazolyl expanded-spectrum cephalosporin, demonstrates potent in vitro activity against Pseudomonas aeruginosa and Pseudomonas cepacia sputum isolates obtained from patients with cystic fibrosis (CF) (1, 7). Pharmacologic evaluations of ceftazidime in these patients have demonstrated altered biodisposition characteristics (8) similar to those observed for other antimicrobial agents in patients with CF (9, 12, 16). Our previous experience assessing the sputum penetration characteristics of ceftazidime in patients with CF revealed sputum drug concentrations which equalled or only marginally exceeded the MIC for pseudomonal isolates (2). Despite these potential pharmacologic limitations, numerous studies have documented the clinical efficacy of ceftazidime monotherapy in the treatment of acute pulmonary exacerbations experienced by patients with CF (2, 3, 6, 11). These data combined suggest that an increased total daily dose of ceftazidime might improve bacteriologic or patient clinical response. To evaluate this hypothesis, we undertook a randomized double-blind evaluation of the efficacy and tolerability of ceftazidime monotherapy administered in varying dosages to patients with CF who were experiencing an acute pulmonary exacerbation of their disease.(Portions of this work were presented at the 25th Interscience Conference on Antimicrobial Agents and Chemotherapy, Minneapoli...

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Section: Resultsmentioning

confidence: 73%

mentioning

confidence: 70%

mentioning

confidence: 99%

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Randomized double-blind evaluation of ceftazidime dose ranging in hospitalized patients with cystic fibrosis

Reed¹,

Stern²,

O'Brien³

et al. 1987

Antimicrob Agents Chemother

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“…Противосинегнойные пенициллины разных групп примерно одинаковы по эффективности [20]. Из цефало-споринов III поколения высокой эффективностью в отно-шении P. аeruginosa обладает цефтазидим [21].…”

Section: лечение синегнойной инфекцииunclassified

Solution of the Problem of Pseudomonas Infection in Children with Cystic Fibrosis

Simonova¹,

Gorinova²,

Lazareva³

et al. 2014

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“…The potential for development of broad-spectrum beta-lactam resistance by induction or derepression of chromosomal beta-lactamase has been recognized and has prompted recommendations for careful use of these agents to prevent the spread of multiply resistant bacteria (11). In the treatment of pulmonary P. aeruginosa infections with these agents, the detection of resistant isolates by different groups of researchers has been quite variable (2,(4)(5)(6).…”

mentioning

confidence: 99%

Mechanism of Pseudomonas aeruginosa persistence during treatment with broad-spectrum cephalosporins of lung infections in patients with cystic fibrosis

Schryvers

Ogunariwo

Chamberland

et al. 1987

Antimicrob Agents Chemother

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Ceftazidime therapy in patients with cystic fibrosis and multiply-drug-resistant pseudomonas

Cited by 38 publications

References 19 publications

Randomized double-blind evaluation of ceftazidime dose ranging in hospitalized patients with cystic fibrosis

Randomized double-blind evaluation of ceftazidime dose ranging in hospitalized patients with cystic fibrosis

Solution of the Problem of Pseudomonas Infection in Children with Cystic Fibrosis

Mechanism of Pseudomonas aeruginosa persistence during treatment with broad-spectrum cephalosporins of lung infections in patients with cystic fibrosis

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