Antimicrobial activity of ceftolozane–tazobactam tested against gram-negative contemporary (2015–2017) isolates from hospitalized patients with pneumonia in US medical centers

doi:10.1016/j.diagmicrobio.2018.11.021

Diagnostic Microbiology and Infectious Disease

Volume 94, Issue 1, May 2019, Pages 93-102

https://doi.org/10.1016/j.diagmicrobio.2018.11.021 Get rights and content

Highlights

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Treatment of pneumonia in hospitalized patients caused by Pseudomonas aeruginosa and Enterobacteriaceae remains limited.
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The in vitro susceptibility of contemporary isolates, obtained from a large US surveillance study, to ceftolozane–tazobactam and comparators was evaluated.
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Ceftolozane–tazobactam had potent in vitro activity (MIC₉₀, 2 mg/L) against P. aeruginosa and Enterobacteriaceae causing pneumonia.
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Ceftolozane–tazobactam showed a high susceptibility rate (>80%) against multidrug-resistant and extensively drug-resistant P. aeruginosa and extended-spectrum β-lactamase, non–carbapenem-resistant Enterobacteriaceae isolates from intensive care unit and ventilator-associated bacterial pneumonia subsets.

Abstract

Pseudomonas aeruginosa (n = 1531) and Enterobacteriaceae (n = 2373) clinical isolates from hospitalized patients with pneumonia were collected from 31 US medical centers during 2015–2017. Isolates were susceptibility tested against ceftolozane–tazobactam and comparators by broth microdilution. Results from intensive care unit (ICU) patients and patients with ventilator-associated bacterial pneumonia (VABP) were analyzed separately. Ceftolozane–tazobactam was very active against P. aeruginosa (MIC_50/90, 0.5/2 mg/L; 97.5% susceptible), including multidrug-resistant (87.9% susceptible) and extensively drug-resistant (82.9% susceptible). Ceftolozane–tazobactam inhibited 90.3% of Enterobacteriaceae isolates (MIC_50/90, 0.25/2 mg/L), including non–carbapenem-resistant Enterobacteriaceae isolates with an extended-spectrum β-lactamase phenotype (85.7% susceptible). Ceftolozane–tazobactam activity was stable against P. aeruginosa regardless of the US census division or ICU and VABP subsets (>90%); small differences were noted among Enterobacteriaceae isolates from the Middle Atlantic (range 78.3–88.9%) and West South Central (range 86.4–89.2%) divisions. These in vitro results indicate that ceftolozane–tazobactam may represent a valuable option for hospital-acquired bacterial pneumonia and VABP caused by Enterobacteriaceae and P. aeruginosa in the United States.

Introduction

Pneumonia is one of the leading causes of mortality in the United States, accounting for more than 50,000 deaths in 2015 (CDC, 2017). Optimal treatment of pneumonia involves selecting an empiric antibiotic regimen that provides early appropriate antibiotic coverage and avoiding unnecessary treatment that may lead to adverse drug effects, Clostridium difficile infection, and antibiotic resistance (Jones et al., 2015). Selecting the most appropriate empiric therapy regimen requires knowledge of local epidemiology and antimicrobial susceptibility patterns. In 2016, the Infectious Disease Society of America and the American Thoracic Society recommended empiric coverage of Staphylococcus aureus, Pseudomonas aeruginosa, and other Gram-negative bacilli in patients with hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) (Kalil et al., 2016). Considering that P. aeruginosa isolates are intrinsically less susceptible (S) to several antimicrobial agents, the current clinically available antipseudomonal antibiotics include ceftazidime, cefepime, piperacillin–tazobactam, aztreonam, carbapenems (except ertapenem), fluoroquinolones, aminoglycosides, and polymyxins. However, P. aeruginosa isolates displaying resistance to these agents are not uncommon in the hospital setting, and the prevalence of extended-spectrum β-lactamase (ESBL)–producing Enterobacteriaceae, which are usually resistant to these agents, is increasing worldwide (Biehl et al., 2016).

Since aminoglycosides and polymyxins should be avoided if alternative agents with adequate Gram-negative activity are available (Kalil et al., 2016), carbapenems, new agents, and inhibitor combinations have been suggested in the literature for treating HABP caused by resistant pathogens (Perez and Bonomo, 2012, Rodriguez-Bano et al., 2012). Among these options, ceftolozane–tazobactam has been demonstrated to overcome the most prevalent resistance mechanisms, such as chromosomal Ambler class C cephalosporinase, several ESBLs, loss of the outer membrane porin, and upregulation of efflux pumps. Ceftolozane–tazobactam also demonstrated activity against carbapenem-resistant strains that do not produce carbapenemases (Bassetti et al., 2018, Pfaller et al., 2017). However, this agent is not active against serine carbapenemases, such as Klebsiella pneumoniae carbapenemase (KPC), or metallo-β-lactamases (Sucher et al., 2015).

Ceftolozane–tazobactam is a combination of a new cephalosporin with a well-known β-lactamase inhibitor. It is approved for clinical use in over 50 countries worldwide, including the United States and Europe, for the treatment of complicated intra-abdominal infections (in combination with metronidazole) and complicated urinary tract infections, including pyelonephritis, in adults (EMA, 2015, ZERBAXA, 2016). Ceftolozane–tazobactam has demonstrated acceptable treatment success rates for serious infections caused by P. aeruginosa, including carbapenem-resistant isolates (Dinh et al., 2017, Munita et al., 2017) and ESBL-producing Enterobacteriaceae (Popejoy et al., 2017). A phase 3 clinical trial to assess the safety and efficacy of ceftolozane–tazobactam (3 g every 8 h intravenous, 60-min infusion) compared with meropenem (1 g every 8 h intravenous, 60-min infusion) for the treatment of HABP, including VABP, has met the primary endpoint of noninferiority, although results have not yet been published (ClinicalTrials.gov registration no. NCT02070757).

In this study, we evaluated the activity of ceftolozane–tazobactam against 1531 P. aeruginosa and 2373 Enterobacteriaceae isolates from pneumonia in hospitalized patients (PHP) in US medical centers during 2015–2017. Results were stratified by US census division. Isolates from patients hospitalized in an intensive care unit (ICU) and those with VABP were analyzed separately. The collection included multidrug-resistant (MDR) and extensively drug-resistant (XDR) P. aeruginosa and ESBL-phenotype Enterobacteriaceae isolates.

Section snippets

Frequency of occurrence of bacterial organisms from PHP

Consecutive unique bacterial isolates were cultured from hospitalized patients with pneumonia in a prevalence sampling design as part of the Program to Assess Ceftolozane–Tazobactam Susceptibility (PACTS) surveillance program (Castanheira et al., 2018). Medical records were not available to make epidemiological inferences about the origin of infection. Thus, hospitalized patients with pneumonia include patients hospitalized for any reason and presenting with pneumonia at any point during their

Frequency of occurrence of bacterial organisms from PHP

The frequency was calculated based on the total number of isolates collected from PHP in 2017. Although all organisms were collected, only P. aeruginosa and Enterobacteriaceae isolates were tested for susceptibility to ceftolozane–tazobactam and comparator agents. S. aureus (27.5%) was the most frequent pathogen, followed by P. aeruginosa (24.7%); K. pneumoniae (7.8%), and E. coli (6.5%). Isolates recovered from ICU patients (40.7%) presented similar frequency distributions: S. aureus (26.9%),

Discussion

Pneumonia in hospitalized patients is a challenging infection that requires timely introduction of optimal empiric antimicrobial therapy to achieve good clinical outcomes, especially among patients in need of intensive care or mechanical ventilation. The frequency distribution of organisms in the 2015–2017 surveillance program presented in this study is very similar to that previously reported for health care–associated pneumonia and VABP (Kalil et al., 2016, Sievert et al., 2013). It is

Funding information

This study was performed by JMI Laboratories and supported by Merck & Co., Inc., which included funding for services related to preparing this manuscript.

JMI Laboratories contracted to perform services in 2017 for Achaogen, Allecra Therapeutics, Allergan, Amplyx Pharmaceuticals, Antabio, API, Astellas Pharma, AstraZeneca, Athelas, Basilea Pharmaceutica, Bayer AG, BD, Becton, Dickinson and Co., Boston Pharmaceuticals, CEM-102 Pharma, Cempra, Cidara Therapeutics, Inc., CorMedix, CSA Biotech,

Conflict of interest

The authors declare no conflicts of interest.

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Activity of ceftolozane-tazobactam against Pseudomonas aeruginosa and Enterobacteriaceae isolates collected from respiratory tract specimens of hospitalized patients in the United States during 2013 to 2015
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Breakpoint tables for interpretation of MIC's and zone diameters. Version 8.0

Cited by (37)

A single- and multiple-dose study to characterize the pharmacokinetics, safety, and tolerability of ceftolozane/tazobactam in healthy Chinese participants
2023, International Journal of Antimicrobial Agents
Ceftolozane/tazobactam (C/T) is approved in several countries to treat complicated urinary tract infections, complicated intra-abdominal infections, and nosocomial pneumonia. There is a paucity of pharmacokinetics and safety data for C/T in Chinese participants. This study evaluated the pharmacokinetics, safety, and tolerability of C/T in 12 healthy Chinese participants after three single administrations of increasing doses (0.75 g, 1.5 g, and 3 g) and multiple administrations of 1.5 g C/T every 8 h for 3 days. After single doses, maximum concentrations of ceftolozane and tazobactam were reached by the end of the 1-h infusion and declined in a biphasic manner thereafter, with mean half-lives of 1.9–2.2 h and 0.74–0.95 h, respectively. Volume of distribution (V_d) and renal clearance (CL) were consistent across the three single-dose levels for ceftolozane (V_d, 15.8–19.5 L; CL, 5.68–6.09 L/h) and tazobactam (V_d, 23.3–28.6 L; CL, 20.8–23.5 L/h). Area under the concentration–time curve (AUC) extrapolated to infinity (ceftolozane, 88.1–328 h∙μg/mL; tazobactam, 10.7–48.0 h∙μg/mL) increased in a dose-dependent manner. After multiple doses over 3 days, AUC from time 0 to 8 h, and concentration at the end of infusion were similar to single-dose measurements (geometric mean ratios, 0.87–1.01 for both drugs). C/T was well tolerated, with no serious adverse events or discontinuations reported; all adverse events were mild. The pharmacokinetics and safety/tolerability of C/T in healthy Chinese participants was comparable to that in previous studies in other populations, supporting the use of C/T for the treatment of Chinese patients.
Multicenter surveillance of antimicrobial susceptibilities and resistance mechanisms among Enterobacterales species and non-fermenting Gram-negative bacteria from different infection sources in Taiwan from 2016 to 2018
2022, Journal of Microbiology, Immunology and Infection
Citation Excerpt :
Contrary to the 2013 Spanish survey demonstrating 87.2% susceptibility of overall Enterobacter isolates to C/T,39 C/T exhibited moderate in vitro activity (susceptibility rate, 65.7%) against our cIAI isolates of Enterobacter species. In spite of being markedly different from one US survey,31 as shown in the other study,40 C/T was more active against the ESBL alone producers of cIAI-related E. coli than K. pneumoniae (79.4% vs. 31.3%; P = 0.002). Nevertheless, these susceptibility rates of C/T against ESBL producers of this study were significantly lower than those addressed by Livermore et al. in the UK study.41
To explore the in vitro antimicrobial susceptibility among clinically important Gram-negative bacteria (GNB) in Taiwan.
From 2016 through 2018, a total of 5458 GNB isolates, including Escherichia coli (n = 1545), Klebsiella pneumoniae (n = 1255), Enterobacter species (n = 259), Pseudomonas aeruginosa (n = 1127), Acinetobacter baumannii complex (n = 368), and Stenotrophomonas maltophilia (n = 179), were collected. The susceptibility results were summarized by the breakpoints of minimum inhibitory concentration (MIC) of CLSI 2020, EUCAST 2020 (for colistin), or published articles (for ceftolozane/tazobactam). The resistance genes among multidrug-resistant (MDR) or extensively drug-resistant (XDR)-GNB were investigated by multiplex PCR.
Significantly higher rates of non-susceptibility (NS) to ertapenem and carbapenemase production, predominantly KPC and OXA-48-like beta-lactamase, were observed in Enterobacterales isolates causing respiratory tract infection than those causing complicated urinary tract or intra-abdominal infection (12.7%/3.44% vs. 5.7%/0.76% or 7.7%/0.97%, respectively). Isolates of Enterobacter species showed higher rates of phenotypic extended-spectrum β-lactamase and NS to ertapenem than E. coli or K. pneumoniae isolates. Although moderate activity (54–83%) was observed against most potential AmpC-producing Enterobacterales isolates, ceftolozane/tazobactam exhibited poor in vitro (44.7–47.4%) activity against phenotypic AmpC Enterobacter cloacae isolates. Additionally, 251 (22.3%) P. aeruginosa isolates exhibited the carbapenem-NS phenotype, and their MDR and XDR rate was 63.3% and 33.5%, respectively. Fifteen (75%) of twenty Burkholderia cenocepacia complex isolates were inhibited by ceftolozane/tazobactam at MICs of ≤4 μg/mL.
With the increase in antibiotic resistance in Taiwan, it is imperative to periodically monitor the susceptibility profiles of clinically important GNB.
Evaluating the emergence of nonsusceptibility among Pseudomonas aeruginosa respiratory isolates from a phase-3 clinical trial for treatment of nosocomial pneumonia (ASPECT-NP)
2021, International Journal of Antimicrobial Agents
Objectives: The emergence of nonsusceptibility to ceftolozane/tazobactam and meropenem was evaluated among Pseudomonas aeruginosa (P. aeruginosa) lower respiratory tract isolates obtained from participants in the ASPECT-NP clinical trial.
Methods: ASPECT-NP was a phase-3, randomised, double-blind, multicentre trial that demonstrated noninferiority of 3 g ceftolozane/tazobactam q8h versus 1 g meropenem q8h for treatment of ventilated hospital-acquired/ventilator-associated bacterial pneumonia. Molecular resistance mechanisms among postbaseline nonsusceptible P. aeruginosa isolates and clinical outcomes associated with participants with emergence of nonsusceptibility were examined. Baseline susceptible and postbaseline nonsusceptible P. aeruginosa isolate pairs from the same participant underwent molecular typing.
Results: Emergence of nonsusceptibility was not observed among the 59 participants with baseline susceptible P. aeruginosa isolates in the ceftolozane/tazobactam arm. Among 58 participants with baseline susceptible P. aeruginosa isolates in the meropenem arm, emergence of nonsusceptibility was observed in 13 (22.4%). Among participants who received ceftolozane/tazobactam and meropenem, 5.1% and 3.4% had a new infection with a nonsusceptible strain, respectively. None of the isolates with emergence of nonsusceptibility to meropenem developed co-resistance to ceftolozane/tazobactam. The molecular mechanisms associated with emergence of nonsusceptibility to meropenem were decreased expression or loss of OprD and overexpression of MexXY.
Conclusions: Among participants with emergence of nonsusceptibility to meropenem, clinical outcomes were similar to overall clinical outcomes in the ASPECT-NP meropenem arm. Ceftolozane/tazobactam was more stable to emergence of nonsusceptibility versus meropenem; emergence of nonsusceptibility was not observed in any participants with baseline susceptible P. aeruginosa who received ceftolozane/tazobactam in ASPECT-NP.
Activity of ceftolozane-tazobactam against Gram-negative pathogens isolated from lower respiratory tract infections in the Asia-Pacific region: SMART 2015-2016
2020, International Journal of Antimicrobial Agents
Citation Excerpt :
In 2019, the US FDA approved a higher dose of ceftolozane/tazobactam (3000 mg intravenously every 8 h) for treatment of hospital-acquired and ventilator-associated bacterial pneumonia. Most surveillance of susceptibility to ceftolozane/tazobactam regimens designed specifically for respiratory pathogens has been conducted outside the Asia-Pacific region [11–13]. Therefore, this multinational study involved the collection of samples from patients with Gram-negative LRTIs at 33 centres in the Asia-Pacific region during 2015-2016.
The aim of this study was to investigate the susceptibility of respiratory Gram-negative bacteria to ceftolozane/tazobactam and other antibiotics in the Asia-Pacific region during 2015-2016. MICs were determined using the CLSI standard broth microdilution method and interpreted accordingly. Pseudomonas aeruginosa (1574 isolates), Klebsiella pneumoniae (1226), Acinetobacter baumannii (627) and Escherichia coli (476) accounted for 73.1% of 5342 Gram-negative respiratory pathogens. Susceptibility to ceftolozane/tazobactam of individual Enterobacteriaceae was >80%, except for Enterobacter cloacae (76.6%). Ceftolozane/tazobactam inhibited 81.9% of K. pneumoniae and 91.9% of E. coli, with respective MIC₅₀/MIC₉₀ values of 0.5/>32 and 0.25/2 mg/L. For carbapenem-susceptible, ESBL-producing K. pneumoniae and E. coli, susceptibility was 65.5% and 93.3%, respectively, and respective MIC₅₀/MIC₉₀ values were 2/>32 and 0.5/2 mg/L. Bla_{CTX-M-1 group} was most prevalent in selected ESBL-producing K. pneumoniae (40 of 54 isolates) and E. coli (15 of 22 isolates), with ceftolozane/tazobactam susceptibility rates of 50% and 80%, respectively. Bla_SHV-ESBL was the second most prevalent, and ceftolozane/tazobactam inhibited 20% of 20 K. pneumoniae isolates with bla_SHV-ESBL. The only effective antibiotics for carbapenem-non-susceptible K. pneumoniae (111 isolates) and E. coli (24 isolates) were amikacin and colistin. Ceftolozane/tazobactam was effective against almost all tested P. aeruginosa and carbapenem-non-susceptible strains, with susceptibility of 92.3% and 72.8%, respectively; the respective MIC₅₀/MIC₉₀ values were 1/4 and 2/>32 mg/L. The high susceptibility of ceftolozane/tazobactam remained in different age groups, patient locations, recovery times and countries, except Vietnam. In conclusion, ceftolozane/tazobactam was effective against most respiratory Gram-negative pathogens in the Asia-Pacific region; however, the emergence of carbapenem resistance mandates ongoing surveillance.
Comparison of ceftazidime-avibactam and ceftolozane-tazobactam in vitro activities when tested against gram-negative bacteria isolated from patients hospitalized with pneumonia in United States medical centers (2017–2018)
2020, Diagnostic Microbiology and Infectious Disease
Citation Excerpt :
In contrast, resistance to ceftolozane-tazobactam can be caused by most clinically relevant carbapenemases, including KPC enzymes, which are fairly common in some parts of the United States (Tangden and Giske 2015; Castanheira et al. 2016; Satlin et al. 2017). Moreover, ceftolozane-tazobactam has shown limited activity against some ESBL-producing K. pneumoniae (Carvalhaes et al., 2019; van Duin and Bonomo, 2016). The fact that the criteria used to categorize a bacterial isolate as clinically significant were not defined in the study protocol and were based on local algorithms is a limitation of the study since these criteria can vary among participating medical centers.
Clinical isolates were consecutively collected from 70 United States medical centers in 2017–2018 and susceptibility tested by reference broth microdilution methods at a central laboratory. The most active agents against Enterobacterales (n = 3269) were ceftazidime-avibactam (99.9% susceptible), amikacin (98.7% susceptible), meropenem (97.4% susceptible), and tigecycline (94.6% susceptible), but only ceftazidime-avibactam and tigecycline retained good activity (≥90% susceptible) against carbapenem-resistant Enterobacterales (97.5% and 92.4% susceptible, respectively). The most active agents against multidrug-resistant (MDR) Enterobacterales were ceftazidime-avibactam (99.2% susceptible) and amikacin (90.9% susceptible), whereas ceftolozane-tazobactam and meropenem were active against only 53.8% and 78.1% of these organisms, respectively. Among ESBL-producing Enterobacterales (excluding carbapenemase-producing), susceptibility rates for ceftazidime-avibactam, ceftolozane-tazobactam, and meropenem were 100.0%, 84.1%, and 98.9%, respectively. Ceftazidime-avibactam and ceftolozane-tazobactam were very active against P. aeruginosa (n = 2215) and exhibited similar susceptibility rates (96.0% and 95.9% susceptible, respectively), including against meropenem-nonsusceptible (87.2% and 87.3% susceptible, respectively) and MDR (83.5% and 83.7% susceptible, respectively) isolates.
Evaluation of in vitro activity of ceftolozane–tazobactam against recent clinical bacterial isolates from Brazil – the EM200 study
2020, Brazilian Journal of Infectious Diseases
Citation Excerpt :
As a regional surveillance network that collected 2410 pathogens from selected medical centers, the study does not provide a population-based data, nor information about the incidence of infections in a given region. In conclusion, ceftolozane–tazobactam has shown satisfactory activity against a great variety of microorganisms analyzed, especially when respiratory tract is the infection site as reported in clinical studies, showing promising results even against resistant strains.17,21,45,46 The activity of ceftolozane–tazobactam is specially observed against P. aeruginosa, E. coli, and other Enterobacterales.
The emergence of antibiotic resistance is increasing and there are few effective antibiotics to treat infections caused by resistant and multidrug resistant bacterial pathogens. This study aimed to evaluate the in vitro activity of ceftolozane–tazobactam against clinical bacterial isolates from Brazil.
A total of 673 Gram-negative bacterial isolates including Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and other Enterobacterales collected from 2016 to 2017 were tested, most of them isolated from patients in intensive care units. Minimum inhibitory concentrations (MIC_50/90) were determined by broth microdilution for amikacin, aztreonam, cefepime, cefotaxime, cefoxitin, ceftolozane–tazobactam, ceftazidime, ceftriaxone, ciprofloxacin, colistin, ertapenem, imipenem, levofloxacin, meropenem, and piperacillin-tazobactam using dried panels. Antimicrobial susceptibility results were interpreted according to Clinical and Laboratory Standards Institute criteria.
Susceptibility rates to ceftolozane–tazobactam ranged from 40.4% to 94.9%. P. aeruginosa susceptibility rate to ceftolozane–tazobactam was 84.9% (MIC_50/90, 1/16 μg/mL) and 99.2% to colistin. For E. coli, ceftolozane–tazobactam inhibited 94.9% (MIC_50/90, 0.25/1 μg/mL) of the microorganisms. The susceptibility rate of K. pneumoniae to ceftolozane–tazobactam was 40.4% (MIC_50/90, 16/>32 μg/mL). Other Enterobacterales have shown susceptibility rates of 81.1% (MIC_50/90, 0.5/16 μg/mL) to ceftolozane–tazobactam, 93.9% to meropenem, 90.9% to amikacin (90.9%), and 88.6% to ertapenem. In non-carbapenemase producing isolates, AmpC mutations were found three isolates.
Ceftolozane–tazobactam has shown relevant activity against a large variety of the analyzed microorganisms collected from multiple centers in Brazil, showing promising results even in multidrug resistant strains.

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Diagnostic Microbiology and Infectious Disease

Highlights

Abstract

Introduction

Section snippets

Frequency of occurrence of bacterial organisms from PHP

Frequency of occurrence of bacterial organisms from PHP

Discussion

Funding information

Conflict of interest

References (25)

Use of ceftolozane/tazobactam as salvage therapy for infections due to extensively drug-resistant Pseudomonas aeruginosa

Int J Antimicrob Agents

Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance

Clin Microbiol Infect

New antibiotics for ventilator-associated pneumonia

Curr Opin Infect Dis

Colonization and infection with extended spectrum beta-lactamase producing Enterobacteriaceae in high-risk patients - review of the literature from a clinical perspective

Crit Rev Microbiol

Prevalence of beta-lactamase-encoding genes among Enterobacteriaceae bacteremia isolates collected in 26 U.S. hospitals: report from the SENTRY antimicrobial surveillance program (2010)

Antimicrob Agents Chemother

Activity of ceftolozane-tazobactam against Pseudomonas aeruginosa and Enterobacteriaceae isolates collected from respiratory tract specimens of hospitalized patients in the United States during 2013 to 2015

Antimicrob Agents Chemother

Antibiotic resistance threats in the United States

Pneumonia

M07Ed11E. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard: eleventh edition

M100Ed28E. Performance standards for antimicrobial susceptibility testing: 28th informational supplement

Zerbaxa ®. Annex I. Summary of product characteristics

Breakpoint tables for interpretation of MIC's and zone diameters. Version 8.0

Cited by (37)

A single- and multiple-dose study to characterize the pharmacokinetics, safety, and tolerability of ceftolozane/tazobactam in healthy Chinese participants

Multicenter surveillance of antimicrobial susceptibilities and resistance mechanisms among Enterobacterales species and non-fermenting Gram-negative bacteria from different infection sources in Taiwan from 2016 to 2018

Evaluating the emergence of nonsusceptibility among Pseudomonas aeruginosa respiratory isolates from a phase-3 clinical trial for treatment of nosocomial pneumonia (ASPECT-NP)

Activity of ceftolozane-tazobactam against Gram-negative pathogens isolated from lower respiratory tract infections in the Asia-Pacific region: SMART 2015-2016

Comparison of ceftazidime-avibactam and ceftolozane-tazobactam in vitro activities when tested against gram-negative bacteria isolated from patients hospitalized with pneumonia in United States medical centers (2017–2018)

Evaluation of in vitro activity of ceftolozane–tazobactam against recent clinical bacterial isolates from Brazil – the EM200 study