Antimicrobial susceptibility of ceftolozane-tazobactam against multidrug-resistant Pseudomonas aeruginosa in Melbourne, Australia (2023)

partial fragment


In an era of rising rates of multidrug resistant (MDR) organisms, new antimicrobials targeting some of the most problematic bacteria such asPseudomonas aeruginosa, urgent need. Ceftolozane-tazobactam (C/T) is an antimicrobial combination approved for the treatment of intra-abdominal infections (in combination with metronidazole), complicated urinary tract infections, and hospital-acquired and ventilator-associated pneumonia. 1, 2, 3 C/T is also recommended for treatment

bacterial isolate

continuouslyPseudomonas aeruginosaIsolates were recovered from clinical specimens over a 7-month period (December 2016 to June 2017) at Alfred Health in Melbourne, Australia. The isolate consists of matt and mucilage forms and is stored in glycerol broth.

–80ºC. Repeat isolates from the same patient were included if they had different morphotypes and/or susceptibility profiles (determined by Vitek 2; BioMérieux, France) and were collected more than one week apart. institutional ethics

Clinical isolates

A total of 163 consecutive respiratory isolates (Table 1) were collected from 113 patients over a 7-month period, with 39 patients contributing to isolation of more than one distinct antimicrobial susceptibility signature and/or colony morphology strain. Most are isolated from sputum (n=144, 88.3%), and the rest came from bronchoalveolar lavage. Median age was 33.9 years (interquartile range 27.4-43.8 years), 55.8% were male, 84.1% (n=95) patients were diagnosed with CF.

Broth Microdilution Antimicrobial Susceptibility



In the researchPseudomonas aeruginosaOf the clinical isolates, we found that 81.6% were sensitive to C/T. Importantly, even in the MDR subset (defined as resistance to ≥ 3 classes of antimicrobials), 88.3% of patients remained susceptible to C/T. In fact, more than a quarter (28.1%) of 32 XDRPseudomonas aeruginosaisolates and 40.7% of meropenem-resistantPseudomonas aeruginosa(defined as MIC >8 mg/L) retained sensitivity to C/T, suggesting its potential as a treatment option for organisms with more extreme drug resistance

in conclusion

Besides colistin, C/T is the most effective antimicrobial against a range of clinical bacteriaPseudomonas aeruginosaIsolates with a range of phenotypes. Results of this study suggest that adding C/T to routine drug susceptibility testing in isolated patientsPseudomonas aeruginosaBacteria from respiratory cultures may be useful in clinical settings and may provide alternative treatment options for MDR, XDR, and meropenem-resistant strains.

Conflicts of Interest and Sources of Funding

This work was supported by an investigator-initiated grant from Merck, which had no involvement in the study design, experiments, or data interpretation. AYP is supported by the Australian NHMRC Practitioner Scholarship (APP1117940) and CCC is supported by the Australian NHMRC Early Career Scholarship (APP1092160). The authors declare no other conflicts of interest to disclose.

Recommended Articles (6)

  • research article

    Neuroendocrine hyperplasia in mucinous borderline ovarian tumors

    Pathology, Volume 55, Issue 4, 2023, Pages 571-573

  • research article

    Deep learning-based speed bump detection and characterization using smartphone sensors

    Ubiquitous and Mobile Computing, Volume 92, 2023, Article 101805

    In recent years, due to the widespread use of smartphones pre-installed with various sensors, a lot of research has been done on road surface anomaly detection. Existing literature mainly focuses on speed bumps, potholes, and manholes, without providing any information on speed bump types. There are four main types of speed bumps, namely sinusoidal, flat top, thermoplastic and domed. The decision to deploy a particular type is made based on the location and speed restrictions in the area. In this article, we not only detect speed bumps, but also identify speed bump types. We first collected a speed bump dataset from smartphone sensors and performed a series of dataset transformations. Using this dataset, we propose and experiment a deep learning-based speed bump detection and characterization system, which is able to achieve test accuracies of 98.92% and 95%, respectively. This work could not only help governments and policy makers identify illegal speed bumps, but also help reduce the number of road accidents, avoid vehicle damage, and reduce environmental, health and economic losses due to substandard or non-standard crash types . Additionally, this work could be integrated into road navigation apps like Google Maps, Waze, etc. to help determine the best route for a driver.

  • research article

    5-ALA-PDT induces ferroptosis in keloid fibroblasts via ROS, accompanied by downregulation of xCT, GPX4

    Photodiagnosis and Photodynamic Therapy, 2023, Article 103612

    Keloids display many oncogenic properties, including uncontrolled invasive growth, high recurrence rates, and similar bioenergetics. 5-Aminolevulinic acid-based photodynamic therapy (5-ALA-PDT) is an effective treatment that exerts cytotoxic effects through the generation of reactive oxygen species (ROS) associated with lipid peroxidation and ferroptosis. Here, we explored the potential mechanism of 5-ALA-PDT against keloids. We found that 5-ALA-PDT resulted in increased levels of ROS and lipid peroxidation in keloid fibroblasts, accompanied by downregulation of xCT and GPX4, which was associated with antioxidant effects and suppression of ferroptosis. These results may suggest that 5-ALA-PDT treatment increases ROS while inhibiting xCT and GPX4, thereby promoting lipid peroxidation to induce ferroptosis in keloid fibroblasts.

  • research article

    A Loss Queuing Game for Charging Performance Evaluation of Electric Vehicles

    Performance Evaluation, 2023, Section 102350

    Electric vehicle (EV) users' demand for electricity from charging stations (CS) is increasing dramatically. However, EV users still face limited resources at charging stations, both in terms of the number of parking spaces equipped with charging points and in terms of available electricity. This paper discusses the problem of an EV user choosing a CS among two CSs in a competitive environment. The randomness of CS arrival and departure is modeled by the queuing system. A queuing game is studied in which EV users are players and the CS providing the highest expected energy is selected. Theory provides an approximation of the expected energy received at the CS, and the quality of this approximation is numerically illustrated and analyzed by means of simulations. The existence and uniqueness of the game equilibrium are proved, and the bound of the price of anarchy (PoA) is given. In addition, the model is simulated using a discrete event frame and provides a sensitivity analysis of the system's key metrics to the average downtime and power adjustment factors. The results show that the utility of EV users at equilibrium is close to the optimal utility. This research could help charge point operators (CPOs) design incentives for EV users, such as limiting parking time, thereby increasing the social welfare of EV users.

  • research article

    Recommendations for germline variant confirmation by next-generation sequencing: a joint report of the Society for Molecular Pathology and the National Association of Genetic Counselors

    Journal of Molecular Diagnostics, 2023

    Clinical laboratory implementation of next-generation sequencing (NGS)-based genetic testing for constitutional fitness has been rapid and widespread. In the absence of widely adopted comprehensive guidelines, NGS practice remains highly variable between laboratories. An ongoing discussion in the field is whether, and to what extent, orthogonal confirmation of NGS-identified genetic variants is necessary or helpful. The Clinical Practice Committee of the Society for Molecular Pathology convened the NGS Germline Variant Confirmation Working Group to assess the current evidence on orthogonal confirmation and develop recommendations to standardize orthogonal confirmation practices to support high-quality patient care. Based on the results of a literature survey, a survey of laboratory practice, and a consensus of subject matter experts, eight recommendations were developed to provide a common framework for clinical laboratory professionals to develop or refine individualized laboratory policies and procedures regarding orthogonal confirmation of NGS assays germline variation.

  • research article

    Molecular epidemiology, clinical features and significance of routine detection of Shiga toxin in gastroenteritis specimens

    Pathology, 2023

    After the introduction of fecal multiplex PCR including the following targetsstx1andstx2gene, we foundstxDuring the 31-month period from 2018 to 2020, the gene was detected in 120 samples from 111 patients, resulting in 14,179 independent tests. proportionstx1only tostx2only tostx1andstx235%, 22% and 42%, respectively. Of the 54 culture-positive specimens, 33 different serotypes were identified, with the predominant serotype being O157:H7 (19%). Clinical data were available for 82 patients; we found high rates of fever (35%), bloody diarrhea (34%), acute kidney injury (27%), hospitalization (80%), and stool co-pathogen detection (23%) . Only one patient developed hemolytic uremic syndrome. we found withstxGenotype and any specific symptoms or complications. We found that serotypes O157:H7 and O26:H11 were significantly associated with bloody stools but not with any other symptoms or complications.

(Video) Cenário atual das infecções osteoarticulares por microorganismos MDR/XDR

© 2023 Royal Australian College of Pathologists. Published by Elsevier B.V. all rights reserved.


Is Ceftolozane-tazobactam good for MDR Pseudomonas? ›

Ceftolozane-tazobactam appeared to be effective in the treatment of multidrug-resistant P aeruginosa infections, particularly when initiated early after the onset of infection.

What is the drug of choice for treating drug resistant Pseudomonas aeruginosa? ›

Pseudomonas infection can be treated with a combination of an antipseudomonal beta-lactam (eg, penicillin or cephalosporin) and an aminoglycoside. Carbapenems (eg, imipenem, meropenem) with antipseudomonal quinolones may be used in conjunction with an aminoglycoside.

What is the breakpoint of Ceftolozane-tazobactam for Pseudomonas? ›

Ceftolozane-tazobactam inhibited 96.3% of the 1,576 P. aeruginosa isolates deemed to be the probable cause of pneumonia among patients hospitalized in the United States at the current CLSI breakpoint criteria (MIC, ≤4/4 μg/ml).

What generation is Ceftolozane-tazobactam? ›

In summary, ceftolozane/tazobactam and ceftazidime/avibactam are 2 new second-generation cephalosporin/β-lactamase inhibitor combinations.

Does Ceftolozane cover Pseudomonas? ›

Ceftolozane/tazobactam (C/T) is a novel β-lactam/β-lactamase inhibitor combination targeting Enterobacteriaceae and Pseudomonas aeruginosa (PA).

Which is better Ceftolozane tazobactam or colistin? ›

Conclusion: C-T is associated with a higher rate of clinical cure and lower rate of AKI compared to colistin. Our findings support the preferential use of C-T over colistin-based regimen for treating these infections.

What is the most effective treatment for Pseudomonas aeruginosa? ›

Pseudomonas aeruginosa infections are generally treated with antibiotics.

How do you treat multiresistant Pseudomonas aeruginosa? ›

Standard treatment for infections caused by MDR-P. aeruginosa in patients with CF often includes combination therapy of two intravenous antipseudomonal antibiotics with different mechanisms of action to reduce the chance of selecting for resistant organisms.

What antibiotic is best for Pseudomonas aeruginosa? ›

Pseudomonas aeruginosa

P. aeruginosa is relatively resistant to many antibiotics, but effective antibiotics include imipenem, meropenem, ceftazidime, ciprofloxacin, amikacin, gentamicin, tobramycin, and piperacillin combined with tazobactam.

Which cephalosporin is highly active against Pseudomonas? ›

Abstract. Ceftazidime and Cefoperazone are the two third generation cephalosporins with anti-pseudomonal activity.

What does Ceftolozane tazobactam cover? ›

Ceftolozane/tazobactam, a novel cephalosporin in combination with an established beta-lactamase inhibitor, is approved for the treatment of cIAIs and cUTIs caused by ESBL-producing Enterobacteriaceae species, drug-resistant P. aeruginosa, and some Streptococcus species.

How does Ceftolozane tazobactam work? ›

Ceftolozane is in a class of antibiotics called cephalosporins. It works by killing bacteria. Tazobactam is in a class called beta-lactamase inhibitor. It works by preventing bacteria from destroying ceftolozane.

What is the only 5th generation cephalosporin? ›

Ceftaroline is a novel fifth-generation cephalosporin, which exhibits broad-spectrum activity against Gram-positive bacteria, including MRSA and extensively-resistant strains, such as vancomycin-intermediate S.

Why 4th generation cephalosporin? ›

A fourth-generation cephalosporin antibiotic used in the treatment of infections caused by susceptible bacteria, such as pneumonia, urinary tract infections, and skin infections. An antibiotic indicated in the treatment of a wide variety of infections in the body.

What is 4th generation cephalosporin drugs? ›

Fourth-generation cephalosporins have similar coverage as third-generation cephalosporins but with additional coverage against gram-negative bacteria with antimicrobial resistance, e.g., beta-lactamase.

How much does Zerbaxa cost? ›

The cost for Zerbaxa intravenous powder for injection (1 g-0.5 g) is around $1,530 for a supply of 10 powder for injection, depending on the pharmacy you visit. Quoted prices are for cash-paying customers and are not valid with insurance plans.

What is the difference between Ceftazidime and Ceftolozane? ›

Ceftolozane/tazobactam combines a novel cephalosporin with an established β-lactam β-lactamase inhibitor, whereas ceftazidime/avibactam couples a well-known cephalosporin with a novel non-β-lactam β-lactamase inhibitor. Both tazobactam and avibactam target the active site of serine β-lactamases (Table ​ 1).

How much is Ceftolozane tazobactam? ›

Ceftolozane/tazobactam remained cost-effective at a willingness to pay of $100,000 per QALY compared to piperacillin/tazobactam over a range of input parameter values during one-way and probabilistic sensitivity analysis.

Is there a shortage of Ceftolozane tazobactam? ›

In December 2020, Zerbaxa was recalled as a precaution in all Member States where it was marketed, and manufacture was temporarily stopped while the issue was being investigated. As a result, shortages occurred.

What brands are Ceftolozane tazobactam? ›

Ceftolozane/tazobactam, sold under the brand name Zerbaxa, is a combination antibiotic medication used for the treatment of complicated urinary tract infections and complicated intra-abdominal infections in adults.

Why is colistin seen as a last resort in antibiotic therapy? ›

If colistin resistance spreads to bacteria that are already resistant to all other antibiotics, those bacteria could cause truly untreatable infections. We cannot keep bacteria from changing; bacteria will inevitably find ways of resisting the antibiotics developed by humans.

What is the first line antibiotic for Pseudomonas aeruginosa? ›

An aminoglycoside with a beta-lactam penicillin is usually considered to be the first line treatment.

What is the success rate of treatment for Pseudomonas aeruginosa? ›

The overall treatment success rate was 79.1%. All but one patient were treated with a combination of surgery and antibiotic therapy. The antibiotic treatment had a mean duration of 45 days (range, 21-90 days). Single-antibiotic therapy was preferred in nearly all cases.

Why is the treatment of Pseudomonas aeruginosa so difficult? ›

Infection caused by this organism are difficult to treat because of the presence of its innate resistance to many antibiotics (β-lactam and penem group of antibiotics), and its ability to acquire further resistance mechanism to multiple class of antibiotics, including Beta-lactams, aminoglycosides and fluoroquinolones.

What is a multi drug resistant Pseudomonas aeruginosa? ›

Pseudomonas aeruginosa is a common cause of healthcare-associated infections including pneumonia, bloodstream infections, urinary tract infections, and surgical site infections. Some P. aeruginosa are becoming more resistant to even antibiotics of last resort, and are described as multidrug-resistant.

How long does it take to cure Pseudomonas aeruginosa? ›

aeruginosa infections can be easily treated with antibiotics. Treating severe hospital-associated P. aeruginosa infections can be difficult, however, because some bacterial strains show resistance to antibiotics. Antibiotics are usually administered for between 7 and 14 days.

Can Pseudomonas in lungs be cured? ›

If you have a Pseudomonas infection, it can usually be treated effectively with antibiotics. But sometimes the infection can be difficult to clear completely.

What antibiotic kills Pseudomonas in lungs? ›

Normally, antibiotics are less effective against bacteria growing in biofilms; azithromycin has shown a potent efficacy in cystic fibrosis patients chronically infected with P. aeruginosa and improved their lung function. The present study was conducted to evaluate the effect of azithromycin on P. aeruginosa biofilm.

How long do you take IV antibiotics for Pseudomonas? ›

Pseudomonas aeruginosa bacteremia is a severe infection, often treated with long-course (~ 14 days) antibiotics.

What are the third generation cephalosporins for Pseudomonas? ›

Pseudomonas aeruginosa is susceptible to a subgroup of third generation agents including ceftazidime, cefoperazone, and the experimental agents cefpirome and cefpiramide. Penetration into the cerebrospinal fluid is excellent especially for cefotaxime, ceftazidime, ceftriaxone, and ceftizoxime.

What type of cephalosporin has a least effect on Pseudomonas aeruginosa? ›

Ceftobiprole has anti-pseudomonal activity and appears to be less susceptible to development of resistance. Ceftaroline has also been described as "fifth-generation" cephalosporin, but does not have the activity against Pseudomonas aeruginosa or vancomycin-resistant enterococci that ceftobiprole has.

Do third generation cephalosporins cover Pseudomonas? ›

For specific therapy, they are active against gram-negative meningitis, Lyme disease, Pseudomonas pneumonia, gram-negative sepsis, Streptococcal endocarditis, melioidosis, penicillinase-producing Neisseria gonorrhea, chancroid, and gram-negative osteomyelitis.

Is Ceftolozane tazobactam 5th generation? ›

Ceftolozane is a cephalosporin antibiotic used to treat complicated intra-abdominal infections in combination with metronidazole, complicated urinary tract infections, and hospital-acquired pneumonia. Ceftolozane is a semi-synthetic broad-spectrum fifth generation cephalosporin.

What is the generic name for Ceftolozane tazobactam? ›

Zerbaxa (ceftolozane/tazobactam) dosing, indications, interactions, adverse effects, and more.

Is Ceftolozane tazobactam FDA approved? ›

The U.S. Food and Drug Administration today approved a new indication for the previously FDA-approved drug, Zerbaxa (ceftolozane and tazobactam) for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) in patients 18 years and older.

Why is tazobactam used in antibiotic therapy? ›

Tazobactam inhibits the action of bacterial beta-lactamase producing organisms, which are normally resistant to beta-lactam antibiotics. This augments the effects of antibiotics which would otherwise not be effective in treating certain infections.

Does tazobactam stop bacteria from destroying piperacillin? ›

Kabi Injection is used for

Piperacillin is an antibiotic that kills many types of bacteria. Tazobactam belongs in the penicillin group but does not have activity against bacteria. It helps piperacillin to overcome bacteria which have become resistant to piperacillin.

What drug class is Ceftolozane tazobactam? ›

Ceftolozane and tazobactam combination is an antibiotic that belongs to the group of medicines known as cephalosporins and beta-lactamase inhibitors.

What antibiotics treat multidrug resistant Pseudomonas? ›

While many approved and pipeline antibiotics have activity against wild-type P. aeruginosa, only four new antibiotics have promising activity against MDR P. aeruginosa: ceftazidime-avibactam (Avycaz®), ceftolozane-tazobactam (Zerbaxa®), cefiderocol, and imipenem-cilastatin/relebactam.

Does tazobactam cover Pseudomonas? ›

Background: Piperacillin-tazobactam is frequently used to treat Pseudomonas aeruginosa infections in critically ill patients.

What is Ceftolozane tazobactam used to treat? ›

The combination of ceftolozane and tazobactam is used to treat certain infections including urinary tract infections and infections of the abdomen (stomach area). It is also used to treat certain types of pneumonia that developed in people who are on ventilators or who were in a hospital.

Which antibiotic is best for Pseudomonas species? ›

Pseudomonas aeruginosa

aeruginosa is relatively resistant to many antibiotics, but effective antibiotics include imipenem, meropenem, ceftazidime, ciprofloxacin, amikacin, gentamicin, tobramycin, and piperacillin combined with tazobactam.

Why is Pseudomonas aeruginosa difficult to treat? ›

Infection caused by this organism are difficult to treat because of the presence of its innate resistance to many antibiotics (β-lactam and penem group of antibiotics), and its ability to acquire further resistance mechanism to multiple class of antibiotics, including Beta-lactams, aminoglycosides and fluoroquinolones.

What is the fastest way to get rid of Pseudomonas? ›

Pseudomonas aeruginosa infections are generally treated with antibiotics.

What is the first line treatment for Pseudomonas aeruginosa? ›

An aminoglycoside with a beta-lactam penicillin is usually considered to be the first line treatment.


Top Articles
Latest Posts
Article information

Author: Terence Hammes MD

Last Updated: 25/10/2023

Views: 5363

Rating: 4.9 / 5 (69 voted)

Reviews: 84% of readers found this page helpful

Author information

Name: Terence Hammes MD

Birthday: 1992-04-11

Address: Suite 408 9446 Mercy Mews, West Roxie, CT 04904

Phone: +50312511349175

Job: Product Consulting Liaison

Hobby: Jogging, Motor sports, Nordic skating, Jigsaw puzzles, Bird watching, Nordic skating, Sculpting

Introduction: My name is Terence Hammes MD, I am a inexpensive, energetic, jolly, faithful, cheerful, proud, rich person who loves writing and wants to share my knowledge and understanding with you.