Use of Aerosolized Antibiotics in Patients With Cystic Fibrosis

Campbell, Preston W.; Saiman, Lisa

doi:10.1378/chest.116.3.775

Cited by 47 publications

(27 citation statements)

References 39 publications

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“…While aerosolized high doses of tobramycin or colistin have proven to be beneficial as suppressive therapy in CF patients chronically infected with P. aeruginosa (7), there are no clinical data to support the use of these treatment modalities for S. maltophilia (7).…”

Section: Discussionmentioning

confidence: 99%

Antimicrobial Susceptibility and Synergy Studies of Stenotrophomonas maltophilia Isolates from Patients with Cystic Fibrosis

Gabriel

Zhou

Tabibi

et al. 2004

Antimicrob Agents Chemother

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Stenotrophomonas maltophilia is a newly emerging pathogen being detected with increasing frequency in patients with cystic fibrosis (CF). The impact of this multidrug-resistant organism on lung function is uncertain. The optimal treatment for S. maltophilia in CF patients is unknown. We studied the in vitro activity of ten antimicrobial agents, and conducted synergy studies by using checkerboard dilutions of eight pairs of antimicrobial agents against strains isolated from 673 CF patients from 1996 to 2001. This represents approximately 7 to 23% of the CF patients in the United States who harbor S. maltophilia annually. Doxycycline was the most active agent and inhibited 80% of 673 initial patient isolates, while trimethoprim-sulfamethoxazole inhibited only 16%. High concentrations of colistin proved more active than high concentrations of tobramycin and gentamicin. Serial isolates (n ‫؍‬ 151) from individual patients over time (median, 290 days) showed minimal changes in resistance. Synergistic or additive activity was demonstrated by trimethoprimsulfamethoxazole paired with ticarcillin-clavulanate (65% of strains), ciprofloxacin paired with ticarcillinclavulanate (64% of strains), ciprofloxacin paired with piperacillin-tazobactam (59% of strains), trimethoprimsulfamethoxazole paired with piperacillin-tazobactam (55% of strains), and doxycycline paired with ticarcillinclavulanate (49% of strains). In all, 522 (78%) isolates were multidrug resistant (i.e., resistant to all agents in two or more antimicrobial classes) but 473 (91%) of these were inhibited by at least one antimicrobial combination (median, four; range, one to eight). To determine appropriate treatment for patients with CF, it is important to monitor the prevalence, antimicrobial susceptibility, and clinical impact of S. maltophilia in this patient population.

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Section: Discussionmentioning

confidence: 99%

Antimicrobial Susceptibility and Synergy Studies of Stenotrophomonas maltophilia Isolates from Patients with Cystic Fibrosis

Gabriel

Zhou

Tabibi

et al. 2004

Antimicrob Agents Chemother

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“…There has been a renewed interest in the use of aerosolized antibiotics in the management of CF lung disease (4,28). Aerosolization has the advantage of minimizing systemic absorption and therefore toxicity by allowing increased concentrations of an antimicrobial agent to be delivered directly to the endobronchial site of infection.…”

Section: Discussionmentioning

confidence: 99%

Cathelicidin Peptides Inhibit Multiply Antibiotic-Resistant Pathogens from Patients with Cystic Fibrosis

Saiman

Tabibi

Starner

et al. 2001

Antimicrob Agents Chemother

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124

100

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, three novel alpha-helical peptides derived from SMAP29 and termed ovispirins (OV-1, OV-2, and OV-3), and two derivatives of CAP18 were tested by broth microdilution assays. Their MICs were determined for multiply antibiotic-resistant Pseudomonas aeruginosa (n ‫؍‬ 24), Burkholderia cepacia (n ‫؍‬ 5), Achromobacter xylosoxidans (n ‫؍‬ 5), and Stenotrophomonas maltophilia (n ‫؍‬ 5) strains isolated from CF patients. SMAP29 was most active and inhibited mucoid and nonmucoid P. aeruginosa strains (MIC, 0.06 to 8 g/ml). OV-1, OV-2, and OV-3 were nearly as active (MIC, 0.03 to 16 g/ml), but CAP18 (MIC, 1.0 to 32 g/ml), CAP18-18 (MIC, 1.0 to >32 g/ml), and CAP18-22 (MIC, 0.5 to 32 g/ml) had variable activities. LL37, mCRAMP, and rCRAMP were least active against the clinical isolates studied (MIC, 1.0 to >32 g/ml). Peptides had modest activities against S. maltophilia and A. xylosoxidans (MIC range, 1.0 to > 32 g/ml), but none inhibited B. cepacia. However, CF sputum inhibited the activity of SMAP29 substantially. The effects of peptides on bacterial cell membranes and eukaryotic cells were examined by scanning electron microscopy and by measuring transepithelial cell resistance, respectively. SMAP29 caused the appearance of bacterial membrane blebs within 1 min, killed P. aeruginosa within 1 h, and caused a dose-dependent, reversible decrease in transepithelial resistance within 5 h. The tested cathelicidin-derived peptides represent a novel class of antimicrobial agents and warrant further development as prophylactic or therapeutic agents for CF lung disease.

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“…Similarly, tobramycin inhalation may prevent P. aeruginosa pulmonary infection in CF [148]. Results from a recent consensus conference on the use of aerosolized antibiotics in CF patients [149] and reviews [142,147,150] have been published.…”

Section: Nebulized Antipseudomonal Antibiotic Therapy In Cystic Fibrosismentioning

confidence: 99%

Antibiotic therapy against Pseudomonas aeruginosa in cystic fibrosis: a European consensus

Döring¹,

Conway²,

Heijerman³

et al. 2000

Eur Respir J

557

478

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Cystic fibrosis (CF) is the most common lethal hereditary disorder with autosomal recessive heredity in caucasians. The majority of CF patients suffer from chronic respiratory infection with the opportunistic bacterial pathogen Pseudomonas aeruginosa. No consensus among clinicians has been reached so far concerning antibiotic treatment against P. aeruginosa in CF patients.Consensus answers to 24 important questions in this context, based on current evidence, are presented, given by a panel of 34 European experts. Questions addressed and answered are: The diagnosis of P. aeruginosa lung colonization in CF; The impact of P. aeruginosa on the clinical state of CF patients; The assessment of P. aeruginosa susceptibility against antibiotics and the importance of these results for the clinician; The use of monotherapy versus combination therapy; The development of microbial resistance; The achievement of optimal airway concentrations; The effects of subinhibitory concentrations of antibiotics on P. aeruginosa; Statements on the pharmacokinetics of antibiotics in CF patients; Recommendations for doses and dosing intervals and length of treatment regimens; and Toxic side effects due to repeated antibiotic therapy was addressed.The expert panel answered further questions on the use of fluoroquinolones in children with CF, on the administration of nebulized antibiotics and whether prevention of P. aeruginosa lung colonization is possible in CF using antibiotic therapy.Problems of antibiotic therapy at home and in the hospital were addressed, a consensus statement on regular maintenance treatment, or treatment on demand, was given and different routes of administration of antibiotics were recommended for different clinical situations.Finally, the factors which determine the choice of the antibiotic, the dosage, and the duration of the treatment in cystic fibrosis patients were addressed and the design of future antibiotic studies in the context of Pseudomonas aeruginosa lung infection in cystic fibrosis patients were recommended. Eur Respir J 2000; 16: 749±767.

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Use of Aerosolized Antibiotics in Patients With Cystic Fibrosis

Cited by 47 publications

References 39 publications

Antimicrobial Susceptibility and Synergy Studies of Stenotrophomonas maltophilia Isolates from Patients with Cystic Fibrosis

Antimicrobial Susceptibility and Synergy Studies of Stenotrophomonas maltophilia Isolates from Patients with Cystic Fibrosis

Cathelicidin Peptides Inhibit Multiply Antibiotic-Resistant Pathogens from Patients with Cystic Fibrosis

Antibiotic therapy against Pseudomonas aeruginosa in cystic fibrosis: a European consensus

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