Microbiological activity of ceftolozane/tazobactam, ceftazidime, meropenem, and piperacillin/tazobactam against Pseudomonas aeruginosa isolated from children with cystic fibrosis

Kuti, Joseph L.; Pettit, Rebecca S.; Neu, Natalie; Cies, Jeffrey J.; Lapin, Craig; Muhlebach, Marianne S.; Novak, Kimberly J.; Nguyen, Sean; Saiman, Lisa; Nicolau, David P.

doi:10.1016/j.diagmicrobio.2015.04.012

Cited by 36 publications

(25 citation statements)

References 6 publications

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“…After the initiation of inhalation regimens with TOBI the susceptibility of P. aeruginosa became much lower compared to the susceptibility reported from Spain and Germany regarding aminoglycosides, cephalosporins and fluoroquinolones (at less than 60% susceptibility for all of the three classes) and much higher regarding carbapenems (over 75% susceptibility) as in USA [5]. Additionally, excluding the data for carbapenem, the susceptibility of our strains, from 2009 onwards, is similar to that reported by Kuti et al for multidrugresistant (MDR) P. aeruginosa isolates from CF children with susceptibility to meropenem, ceftazidime, and piperacillin/tazobactam of 46%, 58%, and 50%, respectively [9]. Maybe this could be explained by the indiscriminate use of anti-microbials for home therapy, because in Bulgaria carbapenems, can be used only during hospital stay.…”

Section: Discussionsupporting

confidence: 70%

Antimicrobial susceptibility of Pseudomonas aeruginosa before and after initiation of inhaled tobramycin in Bulgaria

Petrova

Miteva

Lazova

et al. 2016

J Infect Dev Ctries

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Introduction: In aim to achieve better infection control and possible eradication of the pathogens involved in chronic infections of patients with cystic fibrosis (CF) scientists have developed a new way to administer antimicrobials -inhalation. The first and so far the only available inhalable antimicrobial in Bulgaria is inhaled tobramycin (TOBI), introduced in 2009.We aimed to evaluate the antimicrobial susceptibility of Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients before and after initiation of TOBI in the regular treatment regimen. Methodology: We have determined the minimal inhibitory concentration (MIC) of 17 antimicrobials by the E-test (LIOFILCHEM) in sputa samples of 118 CF patients for the period of 2005-2014. The results were interpreted according to the annual Clinical and Laboratory Standards Institute guidelines. Results: In the sputa of 70 patients a total of 102 P. aeruginosa isolates were found. Sixty-eight out of 102 (66.7%) were susceptible to all studied antimicrobials. We divided the isolates in two chronological groups: those collected before the introduction of TOBI as a regular treatment in 2009 and those collected after 2009. A significant reduction (p < 0,001-0,02) in susceptibility for the strains after 2009 was noted towards piperacillin (100% vs 50%), ceftazidime (100% / 77.3%), cefepime (97.9% / 68.2%), amikacin (100% / 63.6%), gentamicin (95.7% / 40.9%), tobramycin (93.6% / 59.1%) and ciprofloxacin (93.6% / 45.5%). Conclusion: The introduction of inhaled tobramycin as a regular therapy for CF patients in Bulgaria lead to a significant change in antimicrobial susceptibility of CF P. aeruginosa.

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Section: Discussionsupporting

confidence: 70%

Antimicrobial susceptibility of Pseudomonas aeruginosa before and after initiation of inhaled tobramycin in Bulgaria

Petrova

Miteva

Lazova

et al. 2016

J Infect Dev Ctries

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“…The MIC 50 and MIC 90 of ceftolozane alone against P. aeruginosa isolates from CF patients have been reported as 0.5 and 2 g/ml, respectively (20). A similar study in children with CF with multidrug-resistant strains demonstrated higher MIC 50 and MIC 90 values of 2 and 8 g/ml, respectively (8). The Food and Drug Administration (FDA) and the European Committee on Antimicrobial Testing (EUCAST) currently define P. aeruginosa susceptibility to ceftolozane-tazobactam as an MIC of Յ4/4 g/ml (26,27).…”

Section: Discussionmentioning

confidence: 56%

“…This antibiotic retains activity against P. aeruginosa isolates not susceptible to other commonly used antipseudomonal agents and has demonstrated excellent penetration into the epithelial lining fluid of healthy volunteers (8,20,21). The pharmacokinetics of ceftolozane-tazobactam have been studied in healthy volunteers, patients with renal dysfunction, and patients with active infections (5,22).…”

Section: Discussionmentioning

confidence: 99%

“…NCT02070757). Compared with other currently available cephalosporins, ceftolozane is intrinsically more stable against the multiple resistance mechanisms employed by P. aeruginosa, such as AmpC ␤-lactamase production and efflux (6)(7)(8). When ceftolozane is combined with tazobactam, an older ␤-lactamase inhibitor, the antimicrobial coverage of ceftolozane-tazobactam (Zerbaxa; Merck & Co., Inc.) broadens to include Gram-negative organisms producing some ␤-lactamases, including certain extended-spectrum ␤-lactamases.…”

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confidence: 99%

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Population Pharmacokinetics and Safety of Ceftolozane-Tazobactam in Adult Cystic Fibrosis Patients Admitted with Acute Pulmonary Exacerbation

Monogue

Pettit

Muhlebach

et al. 2016

Antimicrob Agents Chemother

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dCeftolozane-tazobactam has potent activity against Pseudomonas aeruginosa, a pathogen associated with cystic fibrosis (CF) acute pulmonary exacerbations (APE). Due to the rapid elimination of many antibiotics, CF patients frequently have altered pharmacokinetics. In this multicenter, open-label study, we described the population pharmacokinetics and safety of ceftolozane-tazobactam at 3 g every 8 h (q8h) in 20 adult CF patients admitted with APE. Population pharmacokinetics were determined using the nonparametric adaptive grid program in Pmetrics for R. A 5,000-patient Monte Carlo simulation was performed to determine the probability of target attainment (PTA) for the ceftolozane component at 1.5 g and 3 g of ceftolozanetazobactam q8h across a range of MICs using a primary threshold exposure of 60% free time above the MIC (fT>MIC). In these 20 adult CF patients, ceftolozane and tazobactam concentration data were best described by 2-compartment models, and ceftolozane clearance (CL) was significantly correlated with creatinine clearance (r ‫؍‬ 0.71, P < 0.001). These data suggest that ceftolozane and tazobactam clearance estimates in CF patients are similar to those in adults without CF (ceftolozane CF CL, 4.76 ؎ 1.13 liter/h; tazobactam CF CL, 20.51 ؎ 4.41 liter/h). However, estimates of the volume of the central compartment (V c ) were lower than those for adults without CF (ceftolozane CF V c , 7.51 ؎ 2.05 liters; tazobactam CF V c , 7.85 ؎ 2.66 liters). Using a threshold of 60% fT>MIC, ceftolozane-tazobactam regimens of 1.5 g and 3 g q8h should achieve PTAs of >90% at MICs up to 4 and 8 g/ml, respectively. Ceftolozane-tazobactam at 3 g q8h was well tolerated. These observations support additional studies of ceftolozane-tazobactam for Pseudomonas aeruginosa APE in CF patients. (This study has been registered at ClinicalTrials.gov under identifier NCT02421120.) C ystic fibrosis (CF) is an autosomal recessive genetic disorder that affects multiple organ systems (1). Nearly 1,000 new cases of CF are diagnosed annually in the United States, and more than 75% of these diagnoses are made by the age of 2 (2). Understanding the importance of augmenting airway clearance, aggressively treating infection, and correcting nutrition deficits have collectively increased the median survival from 31 years in 2002 to 41 years in 2013, with approximately half of CF patients being 18 years or older (1, 2). Lungs are the most prominent affected organs, and 85% of CF mortality is attributed to lung disease (3). CF lung disease begins with inflammation of the pulmonary tissues along with impaired airway mucociliary clearance, which consequently results in chronic infection of the airways due to impaired bacterial clearance. Lung function in CF progressively declines with the occurrence of acute episodes of pulmonary exacerbation caused by the organisms chronically occupying the CF airway (3). Common organisms that inhabit the lungs of adult CF patients include Pseudomonas aeruginosa and Staphylococcus aureus, including drug-resista...

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“…The activity of ceftolozane alone against P. aeruginosa isolates with high rates of ␤-lactam susceptibility from chronically infected CF patients was reported in two studies with encouraging results (11,12). Only one study reported the activity of ceftolozane in combination with tazobactam, which is the currently marketed combination (Zerbaxa; Merck & Co., Inc.) (13). To our knowledge, ceftolozane-tazobactam has never been tested against MDR Achromobacter and S. maltophilia isolates from CF patients.…”

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confidence: 99%

In Vitro Activity of Ceftolozane-Tazobactam against Multidrug-Resistant Nonfermenting Gram-Negative Bacilli Isolated from Patients with Cystic Fibrosis

Grohs

Taieb

Morand

et al. 2017

Antimicrob Agents Chemother

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Ceftolozane-tazobactam was tested against 58 multidrug-resistant nonfermenting Gram-negative bacilli (35 Pseudomonas aeruginosa, 11 Achromobacter xylosoxydans, and 12 Stenotrophomonas maltophilia isolates) isolated from cystic fibrosis patients and was compared to ceftolozane alone, ceftazidime, meropenem, and piperacillin-tazobactam. Ceftolozane-tazobactam was the most active agent against P. aeruginosa but was inactive against A. xylosoxydans and S. maltophilia. In time-kill experiments, ceftolozane-tazobactam had complete bactericidal activity against 2/6 clinical isolates (33%).

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Microbiological activity of ceftolozane/tazobactam, ceftazidime, meropenem, and piperacillin/tazobactam against Pseudomonas aeruginosa isolated from children with cystic fibrosis

Cited by 36 publications

References 6 publications

Antimicrobial susceptibility of Pseudomonas aeruginosa before and after initiation of inhaled tobramycin in Bulgaria

Antimicrobial susceptibility of Pseudomonas aeruginosa before and after initiation of inhaled tobramycin in Bulgaria

Population Pharmacokinetics and Safety of Ceftolozane-Tazobactam in Adult Cystic Fibrosis Patients Admitted with Acute Pulmonary Exacerbation

In Vitro Activity of Ceftolozane-Tazobactam against Multidrug-Resistant Nonfermenting Gram-Negative Bacilli Isolated from Patients with Cystic Fibrosis

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