brl-28500 and Pseudomonas-Infections

Acute pulmonary exacerbations (APE) are well-described complications of cystic fibrosis (CF) and are associated with progressive morbidity and mortality. Despite aggressive management with two or more intravenous anti-pseudomonal agents, approximately 25% of exacerbations will result in a loss of lung function. The aim of this review is to provide an evidence-based summary of pharmacokinetic/pharmacodynamic (PK/PD), tolerability, and efficacy studies utilizing anti-pseudomonal cephalosporins (i.e., ceftazidime and cefepime) and penicillins (i.e., piperacillin-tazobactam and ticarcillin-clavulanate) in the treatment of APE and to identify areas where further study is warranted. The ceftazidime and cefepime dosing ranges from the literature are 200-400 mg/kg/day divided every 6-8 hr, maximum 8-12 g/day, and 150-200 mg/kg/day divided every 6-8 hr, up to 6-8 g/day, respectively. The literature supported dosing ranges for piperacillin and ticarcillin are 350-600 mg/kg/day divided every 4 hr, maximum 18-24 g/day of piperacillin component, and 400-750 mg/kg/day divided every 6 hr, up to 24-30 g/day of ticarcillin component, respectively. As a large portion of CF patients will not regain their lung function following an APE, we suggest the need to optimize antibiotic dosing and dosing regimens used to treat an APE in efforts to improve outcomes for CF patients infected with Pseudomonas aeruginosa. Future studies are needed to determine the clinical efficacy of higher than FDA-approved doses of ceftazidime, cefepime, and ticarcillin-clavulanate in APE. The usefulness of high dose piperacillin (>600 mg/kg/day) may be limited due to treatment-related adverse effects. Further understanding of these adverse effects in CF patients is needed.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; Cefepime; Ceftazidime; Cephalosporins; Clavulanic Acids; Cystic Fibrosis; Disease Progression; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Penicillanic Acid; Penicillins; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Pseudomonas Infections; Ticarcillin

Initial antibiotic treatment of extracavitary arterial graft infections is usually empiric or based on Gram's stain findings. Increasing virulence of bacteria causing extracavitary arterial graft infections may render previous choices of antibiotics obsolete. The purposes of this study were to correlate Gram's stain findings of gram-positive bacteria and gram-negative bacteria with wound cultures and provide a microbiologic basis for appropriate initial antibiotic therapy.. Between July 1, 1979 and June 30, 1994, specimens obtained on the day of admission from purulent wounds involving 113 extracavitary arterial graft infections were retrospectively reviewed for Gram's stain and culture and sensitivity results.. Gram's stain findings correlated with final cultures on only 28 of 113 cases (25%), including 20 of 48 pure gram-positive, 2 of 24 pure gram-negative, and 6 of 41 mixed bacterial cultures. Staphylococcus aureus was the most common gram-positive bacteria cultured (43 isolates) and Pseudomonas species was the most common gram-negative bacteria (25 isolates). Bacteria were sensitive to a first-generation cephalosporin in only 32% (36 of 113) of infections. A combination of vancomycin and either ticarcillin-clavulanic acid or ceftazidime, which have minimal toxicity and provide excellent coverage against staphylococci, Pseudomonas, and other gram-negative bacteria, would have covered 96% (109) and 95% (107) of cultured organisms, respectively.. Regardless of Gram's stain findings, current recommendations for initial treatment of extracavitary arterial graft infections should include vancomycin and ceftazidime or ticarcillin-clavulanic acid until final culture and sensitivity results dictate the use of more selective antibiotics.

Topics: Anti-Bacterial Agents; Arteries; Blood Vessel Prosthesis; Ceftazidime; Clavulanic Acids; Drug Therapy, Combination; Humans; Pseudomonas Infections; Retrospective Studies; Staphylococcal Infections; Surgical Wound Infection; Ticarcillin; Transplantation, Autologous; Vancomycin; Veins

While. To determine the risk and explanatory factors of acquiring. Cross-sectional analysis of clinical, bronchoalveolar lavage and treatment data from the Australasian Cystic Fibrosis Bronchoalveolar Lavage study was used to identify predictive factors for detecting. Cross-sectional analysis found that the number of. In young children with CF, completing

Topics: Anti-Bacterial Agents; Bronchoalveolar Lavage; Ceftazidime; Child, Preschool; Ciprofloxacin; Clavulanic Acids; Cross-Sectional Studies; Cystic Fibrosis; Female; Humans; Infant; Longitudinal Studies; Male; Prevalence; Pseudomonas aeruginosa; Pseudomonas Infections; Pulmonary Aspergillosis; Randomized Controlled Trials as Topic; Recurrence; Risk Factors; Ticarcillin; Tobramycin

Aztreonam, cefepime, and ceftazidime are anti-pseudomonal beta-lactam antibiotics which have been previously reported to be administered by continuous infusion (CI) in pediatric CF patients. We present two cases administering intravenous (IV) meropenem and ticarcillin-clavulanate by CI in pediatric CF patients. The delivery of beta-lactam antibiotics via CI should be considered in order to optimize the pharmacodynamics (PD) of beta-lactams in the treatment of acute pulmonary exacerbations (APE).

Topics: Adolescent; Anti-Bacterial Agents; Clavulanic Acids; Cystic Fibrosis; Female; Gram-Negative Bacterial Infections; Humans; Infusions, Intravenous; Meropenem; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Rhodospirillaceae; Thienamycins; Ticarcillin

Earlier reports suggested that Pseudomonas aeruginosa frequent epidemic clones circulating in cystic fibrosis (CF) centres had increased virulence. However, recent data show no consistent associations with virulence, and suggest attenuation of virulence in chronic infection. Changes to infection control programmes in relation to frequent epidemic clones should be based on their frequency, virulence across all age groups and mode of acquisition. The Australian epidemic strain-1 (AES-1) (or the Melbourne epidemic strain) and AES-2 are common in CF clinics in mainland eastern Australia, but not in the environment. Both have shown increased virulence, but there are no data specifically in adults. This study examines the frequency and virulence of P. aeruginosa frequent epidemic clones in the adult CF clinic at Royal Prince Alfred Hospital, Sydney, Australia.. Two hundred and fifty-eight P. aeruginosa isolates from 112 participants were genotyped by pulsed field gel electrophoresis. Ninety-eight patients were followed up for 1 year and associations sought between infection with a frequent epidemic clone, clinical outcome and antibiotic resistance.. Four frequent P. aeruginosa epidemic clones (AES-1, AES-2, S-1, S-2) affected almost 50% of participants. AES-1 predominated (38%). AES-1, AES-2 and S-1 were associated with increased exacerbations and hospital-admission days. AES-1 showed increased resistance to aminoglycosides and ticarcillin-clavulanate.. This study supports the potential threat of frequent P. aeruginosa epidemic clones in adult CF populations.

Topics: Adolescent; Adult; Aminoglycosides; Anti-Bacterial Agents; Aspergillus fumigatus; Australia; Clavulanic Acids; Clone Cells; Comorbidity; Cystic Fibrosis; Female; Follow-Up Studies; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Sputum; Stenotrophomonas maltophilia; Ticarcillin; Young Adult

The aim of cystic fibrosis (CF) care is to improve both the life expectancy and quality of life of patients. However, rising costs and limited resources of health services must be taken into account. There are many different antibiotic strategies for therapy of Pseudomonas aeruginosa infection in CF patients. In this 5-year retrospective study we found that the cost of treatment of initial infection is considerably lower than the cost of treating chronic P. aeruginosa infections. The percentage distribution of costs of antibiotic treatment in relationship to the administration route was considerably different between outpatients and inpatients. We observed an increase in antibiotic costs with the age of the patient and the decrease in FEV(1)values. The implementation of early eradication treatment, in addition to decreasing the prevalence of patients chronically infected by P. aeruginosa, might also bring about a notable decrease in costs.

Topics: Adult; Anti-Bacterial Agents; Ceftazidime; Child, Preschool; Chronic Disease; Ciprofloxacin; Clavulanic Acids; Colistin; Cost of Illness; Cystic Fibrosis; Humans; Meropenem; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Thienamycins; Ticarcillin; Tobramycin

Topics: Child, Preschool; Clavulanic Acids; Cystic Fibrosis; Desensitization, Immunologic; Drug Therapy, Combination; Female; Humans; Infusions, Parenteral; Pneumococcal Infections; Pseudomonas Infections; Sinusitis; Ticarcillin

Topics: beta-Lactamase Inhibitors; Clavulanic Acids; Drug Combinations; Drug Resistance, Microbial; Humans; Male; Middle Aged; Penicillins; Postoperative Complications; Pseudomonas aeruginosa; Pseudomonas Infections; Ticarcillin

The therapeutic effects produced by ticarcillin plus clavulanic acid were compared with those of ticarcillin and clavulanic acid separately against infections in the mouse caused by beta-lactamase-producing bacteria. The infections studied included a pneumonia model, a local tissue infection and pyelonephritis. The distribution of ticarcillin and clavulanic acid in infected animals was evaluated by measurement of the concentrations of the substances present at sites of infection. The results showed that both ticarcillin and clavulanic acid were well-distributed in the mouse and at the doses employed were present at the sites of infection at concentrations of the same order as those obtained in man after administration of ticarcillin/clavulanic acid formulations (Timentin). The protection of ticarcillin by clavulanic acid from inactivation by the beta-lactamases produced in vivo by Bacteroides fragilis, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa was demonstrated by the pronounced bactericidal effects produced by the ticarcillin/clavulanic acid combination against the ticarcillin-refractory infections studied.

Topics: Animals; Bacteroides fragilis; Bacteroides Infections; Clavulanic Acids; Drug Combinations; Klebsiella Infections; Klebsiella pneumoniae; Mice; Penicillin Resistance; Penicillins; Pneumonia; Pseudomonas aeruginosa; Pseudomonas Infections; Pyelonephritis; Species Specificity; Ticarcillin