Treatment of Lower Respiratory Tract Infections Due to Pseudomonas aeruginosa in Patients with Cystic Fibrosis

Scully, Brian E.; Ores, Celia N.; Prince, Alice; Neu, Harold C.

doi:10.1093/clinids/7.supplement_4.s669

Cited by 25 publications

(11 citation statements)

References 19 publications

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“…In this scenario, patients are treated with an appropriate ␤-lactam based on initial susceptibility data, only to fail therapy due to the emergence of AmpC-mediated resistance. This phenomenon has been observed in 14 to 56% of patients treated with antipseudomonal penicillins, penicillin-inhibitor combinations, aztreonam, and extended-spectrum cephalosporins (50,71,94,97,118,147,226,228,235), and emergence of resistance/ clinical failure is observed most frequently with infections outside the urinary tract and in patients with underlying cystic fibrosis and neutropenia. Although combining an aminoglyco- Inducing ␤-lactams, such as cefoxitin and imipenem, cross the outer membrane through porins, enter the periplasmic space, and interact with target PBPs.…”

Section: Clinical Significance Of Ampc Overproductionmentioning

confidence: 99%

“…22,2009 ANTIBACTERIAL-RESISTANT PSEUDOMONAS AERUGINOSA 589 side with an antipseudomonal ␤-lactam is one strategy for preventing the emergence of AmpC-mediated resistance, this combination is not always effective in achieving that goal (97,118,147,226,228,235).…”

Section: Clinical Significance Of Ampc Overproductionmentioning

confidence: 99%

“…The combination of an antipseudomonal ␤-lactam with an aminoglycoside has often been the treatment of choice for this pathogen. However, this combination does not always prevent the emergence of AmpCmediated resistance to the ␤-lactams, and clinical failures are still a risk (97,118,147,226,228,235). Therefore, the search for more effective combinations must be a priority.…”

Section: Preventing Emergence Of Chromosomally Encoded Resistancementioning

confidence: 99%

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Antibacterial-ResistantPseudomonas aeruginosa: Clinical Impact and Complex Regulation of Chromosomally Encoded Resistance Mechanisms

2009

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SUMMARY Treatment of infectious diseases becomes more challenging with each passing year. This is especially true for infections caused by the opportunistic pathogen Pseudomonas aeruginosa, with its ability to rapidly develop resistance to multiple classes of antibiotics. Although the import of resistance mechanisms on mobile genetic elements is always a concern, the most difficult challenge we face with P. aeruginosa is its ability to rapidly develop resistance during the course of treating an infection. The chromosomally encoded AmpC cephalosporinase, the outer membrane porin OprD, and the multidrug efflux pumps are particularly relevant to this therapeutic challenge. The discussion presented in this review highlights the clinical significance of these chromosomally encoded resistance mechanisms, as well as the complex mechanisms/pathways by which P. aeruginosa regulates their expression. Although a great deal of knowledge has been gained toward understanding the regulation of AmpC, OprD, and efflux pumps in P. aeruginosa, it is clear that we have much to learn about how this resourceful pathogen coregulates different resistance mechanisms to overcome the antibacterial challenges it faces.

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Section: Clinical Significance Of Ampc Overproductionmentioning

confidence: 99%

Section: Clinical Significance Of Ampc Overproductionmentioning

confidence: 99%

Section: Preventing Emergence Of Chromosomally Encoded Resistancementioning

confidence: 99%

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Antibacterial-ResistantPseudomonas aeruginosa: Clinical Impact and Complex Regulation of Chromosomally Encoded Resistance Mechanisms

2009

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“…12 Aztreonam has been administered intravenously in the treatment of CF pulmonary exacerbations. [13][14][15] The parenteral formulation of aztreonam (Azactam 1 ) contains arginine, which has been shown to cause airway inflammation after chronic inhaled administration to CF patients. 16 However, a recent study noted that inhalation of a single dose of L-arginine may acutely improve pulmonary function in CF.…”

Section: Introductionmentioning

confidence: 99%

A phase 2 study of aztreonam lysine for inhalation to treat patients with cystic fibrosis and Pseudomonas aeruginosa infection

Retsch‐Bogart¹,

Burns

Otto³

et al. 2007

Pediatric Pulmonology

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Summary. Background: Aztreonam lysine for inhalation (AZLI) is being developed for treatment of CF patients with Pseudomonas aeruginosa airway infection. Methods: This double-blind, randomized, placebo-controlled Phase 2 study evaluated the safety, tolerability and efficacy of 75 and 225 mg AZLI administered BID for 14 days using the eFlow 1 Electronic Nebulizer (Pari Innovative Manufacturers, Inc., Midlothian, VA). Patients were 13 years and older with FEV 1 ! 40% predicted, chronic P. aeruginosa infection, and had used no anti-pseudomonal antibiotics for 56 days. Results: Of 131 patients screened, 105 received AZLI or placebo. Mean age was 26 years and mean FEV 1 percent predicted was 77% at baseline. There was a statistically significant reduction, compared to placebo, in P. aeruginosa CFU density in each AZLI group at Days 7 and 14 (P < 0.001). The planned primary analysis, percent change in FEV 1 at Day 14, demonstrated no statistically significant difference. Post hoc analysis demonstrated significant increase in FEV 1 at Day 7 for the subset of patients with baseline FEV 1 < 75% predicted in the 225 mg AZLI group. Bronchodilator use was associated with greater improvement in FEV 1 , as well as greater reduction in P. aeruginosa bacterial density and higher plasma aztreonam concentrations in the 225 mg AZLI group. Adverse events were similar between placebo and AZLI although there was a trend toward

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“…This activity extends to Pseudomonas aeruginosa, including isolates from patients with cystic fibrosis (19). Early experience with the use of aztreonam in patients with cystic fibrosis has yielded promising results (2,21). However, the customary treatment for the pneumonia associated with pulmonary exacerbations of cystic fibrosis generally includes both a beta-lactam and an aminoglycoside antibiotic.…”

mentioning

confidence: 99%

In vitro activity of aztreonam combined with tobramycin and gentamicin against clinical isolates of Pseudomonas aeruginosa and Pseudomonas cepacia from patients with cystic fibrosis

Bosso

Saxon

Matsen

1987

Antimicrob Agents Chemother

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The in vitro activity of aztreonam combined with tobramycin and with gentamicin was assessed in 78 clinical isolates of Pseudomonas aeruginosa and 11 clinical isolates of Pseudomonas cepacia from patients with cystic fibrosis. Synergy was detected in 56.4% of P. aeruginosa isolates and 60% of P. cepacia isolates with the aztreonam-tobramycin combination and in 49.3% of P. aeruginosa isolates and 81.8% of P. cepacia isolates with the aztreonam-gentamicin combination. No antagonism was observed. These combinations merit clinical evaluation in the treatment of patients with cystic fibrosis.Aztreonam is a monobactam antibiotic with in vitro activity against a number of gram-negative aerobic bacteria (8). This activity extends to Pseudomonas aeruginosa, including isolates from patients with cystic fibrosis (19). Early experience with the use of aztreonam in patients with cystic fibrosis has yielded promising results (2, 21). However, the customary treatment for the pneumonia associated with pulmonary exacerbations of cystic fibrosis generally includes both a beta-lactam and an aminoglycoside antibiotic. Such combinations are used to take advantage of potential synergy and to help prevent or delay the emergence of resistance which is often observed with single-drug therapy. It is likely that aztreonam will find a place in such combination therapy with an aminoglycoside. We therefore studied the in vitro effects of combinations of aztreonam with tobramycin and with gentamicin against clinical isolates of P. aeruginosa and Pseudomonas cepacia from patients with cystic fibrosis. MATERIALS AND METHODSA total of 78 isolates of P. aeruginosa and 11 isolates of P. cepacia obtained from the sputum of patients with cystic fibrosis were identified by standard microbiological methods (5) and stored at room temperature on tryptic soy agar slants without dextrose before being studied. Isolates were transferred to duplicate blood agar plates and checked for purity. They were subsequently transferred to Trypticase soy broth (BBL Microbiology Systems, Cockeysville, Md.) and incubated overnight at 35°C. The turbidity of each bacterial broth suspension was then standardized to that of a 0.5 McFarland standard. From each standardized suspension, 0.1 ml was transferred to 9.9 ml of Mueller-Hinton broth, supplemented with the divalent cations calcium and magnesium (final concentrations, 50 and 25 mg/ml, respectively), yielding a 1:100 dilution.The antibiotics studied were supplied by the following sources: aztreonam, E. R. Squibb & Sons, Princeton, N.J.; gentamicin, Schering Corp., Kenilworth, N.J.; tobramycin, Eli Lilly & Co., Indianapolis, Ind. Stock solutions were prepared from dry powders and used immediately or frozen at -32°C. Frozen solutions of aztreonam were used within 1 * Corresponding author. month, and aminoglycoside solutions were used within 3 months. The antibiotic concentrations tested were twofold dilutions ranging from 1,024 to 0.0156 ,ug/ml for aztreonam and 1,024 to 0.062 jig/ml for tobramycin and gentamicin.MICs were...

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Treatment of Lower Respiratory Tract Infections Due to Pseudomonas aeruginosa in Patients with Cystic Fibrosis

Cited by 25 publications

References 19 publications

Antibacterial-ResistantPseudomonas aeruginosa: Clinical Impact and Complex Regulation of Chromosomally Encoded Resistance Mechanisms

Antibacterial-ResistantPseudomonas aeruginosa: Clinical Impact and Complex Regulation of Chromosomally Encoded Resistance Mechanisms

A phase 2 study of aztreonam lysine for inhalation to treat patients with cystic fibrosis and Pseudomonas aeruginosa infection

In vitro activity of aztreonam combined with tobramycin and gentamicin against clinical isolates of Pseudomonas aeruginosa and Pseudomonas cepacia from patients with cystic fibrosis

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