In vitro activity of ceftolozane-tazobactam against Enterobacterales and Pseudomonas aeruginosa causing urinary, intra-abdominal and lower respiratory tract infections in intensive care units in Portugal: The STEP multicenter study

Abstract Background β-lactamase-producing Enterobacterales (Ebact) frequently co-carry resistance to antimicrobials from other classes, limiting treatment options. Avibactam (AVI) inhibits class A, class C, and some class D serine β-lactamases, while aztreonam (ATM) is refractory to hydrolysis by class B metallo-β-lactamases (MBLs). ATM-AVI is being developed for use against drug-resistant isolates of Ebact, especially those co-producing MBLs and serine β-lactamases. This study evaluated the in vitro activity of ATM-AVI and comparators against Ebact collected in 2017-2019 from patients with lower respiratory tract infections (LRTI) as part of the Antimicrobial Testing Leadership and Surveillance (ATLAS) program. Methods Non-duplicate clinical isolates were collected in 52 countries in Europe, Latin America, Asia/Pacific (excluding mainland China and India), and Middle East/Africa. Susceptibility testing was performed by CLSI broth microdilution and interpreted using CLSI 2021 and FDA (tigecycline) breakpoints. ATM-AVI was tested at a fixed concentration of 4 µg/mL AVI. MDR was defined as resistant (R) to ≥3 of 7 sentinel drugs: amikacin, aztreonam, cefepime, colistin, levofloxacin, meropenem, and piperacillin-tazobactam. PCR and sequencing were used to determine the β-lactamase genes present in all isolates with meropenem MIC >1 µg/mL, and Escherichia coli, Klebsiella spp. and Proteus mirabilis with ATM or ceftazidime MIC >1 µg/mL. Results ATM-AVI was active in vitro against Ebact isolates from LRTI (MIC90, 0.25 µg/mL), with 99.97% of isolates inhibited by ≤8 µg/mL of ATM-AVI, including 100% of isolates that produced MBLs. ATM-AVI tested with MIC90 values of 0.5 µg/mL against subsets of cefepime-nonsusceptible (NS), meropenem-NS, amikacin-NS, colistin-resistant, and MBL-positive Ebact (Table). The tested β-lactam comparators showed susceptibility of < 78% against these subsets of resistant isolates. Results Table Conclusion Based on MIC90 values, ATM-AVI was the most potent agent tested against drug-resistant and MBL-positive subsets of Ebact collected from LRTI. The promising in vitro activity of ATM-AVI warrants further development of this combination for treatment of LRTI caused by drug-resistant Ebact. Disclosures Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Francis Arhin, PhD, Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)

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Multidrug-resistant Pseudomonas aeruginosa lower respiratory tract infections in the intensive care unit: Prevalence and risk factors

Diagnostic Microbiology and Infectious Disease ◽

10.1016/j.diagmicrobio.2017.06.009 ◽

2017 ◽

Vol 89 (1) ◽

pp. 61-66 ◽

Cited By ~ 13

Author(s):

Trang D. Trinh ◽

Evan J. Zasowski ◽

Kimberly C. Claeys ◽

Abdalhamid M. Lagnf ◽

Shravya Kidambi ◽

...

Keyword(s):

Risk Factors ◽

Intensive Care Unit ◽

Pseudomonas Aeruginosa ◽

Intensive Care ◽

Respiratory Tract ◽

Lower Respiratory Tract ◽

Respiratory Tract Infections ◽

Multidrug Resistant ◽

Lower Respiratory Tract Infections ◽

Tract Infections

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Epidemiology of respiratory syncytial virus in children ≤2 years of age hospitalized with lower respiratory tract infections in the Russian Federation: a prospective, multicenter study

Clinical Epidemiology ◽

10.2147/clep.s12279 ◽

2010 ◽

pp. 221

Author(s):

Gudkov

Keyword(s):

Respiratory Syncytial Virus ◽

Respiratory Tract ◽

Multicenter Study ◽

Lower Respiratory Tract ◽

Respiratory Tract Infections ◽

Lower Respiratory Tract Infections ◽

Prospective Multicenter Study ◽

The Russian Federation ◽

Syncytial Virus ◽

Tract Infections

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Predominance of Bacterial Flora Causing Lower Respiratory Tract Infections Following Tracheostomy in Patients of Chettinad Hospital & Research Institute, Chennai, India

Journal of Evolution of Medical and Dental Sciences ◽

10.14260/jemds/2021/606 ◽

2021 ◽

Vol 10 (35) ◽

pp. 2964-2968

Author(s):

Swetha Thirumurthi ◽

Priya Kanagamuthu ◽

Rajasekaran Srinivasan ◽

Bhalaji Dhanasekaran

Keyword(s):

Pseudomonas Aeruginosa ◽

Respiratory Tract ◽

Lower Respiratory Tract ◽

Respiratory Tract Infections ◽

Antibiotic Sensitivity ◽

Klebsiella Pneumonia ◽

Lower Respiratory Tract Infections ◽

Empirical Antibiotics ◽

Tract Infections ◽

Research Institute

BACKGROUND The term tracheostomy refers to forming an opening in the trachea.1,2 Its advantages include easy and direct access to lower respiratory tract, reduced risk of aspiration, faster weaning from ventilation support and improved physical and psychological comfort. But a common problem in tracheostomised patients is increased risk of colonisation of lower respiratory tract by exogenous bacteria because of direct exposure.1,3 This study was done to recognise pathogens in tracheal secretions collected from tracheostomised patients and their antibiotic sensitivity to treat them with appropriate antibiotics. METHODS This prospective study was done in 138 tracheostomised patients from October 2020 to March 2021 in intensive care unit (ICU) of Chettinad Hospital and Research Institute. Under sterile aseptic precautions, Day 0 and Day 7 cultures posttracheostomy was obtained and their antibiotic sensitivity was studied. Data was analysed using Statistical Package for Social Sciences (SPSS version 19) and presented in proportion, mean and standard deviation (Descriptive statistics). RESULTS In this study, of the 56 cases who had growth in their culture and sensitivity reports on day 0, the most common organism was Pseudomonas aeruginosa (33.9 %) sensitive to imipenem (94.7 %) followed by klebsiella (25 %) sensitive to teicoplanin, vancomycin, amikacin, cefoperazone/tazobactam, linezolid and piperacillin/tazobactam. On day 7, the growth of organisms isolated in tracheal culture got reduced from 56 cases to 16 cases. The prevalence of Pseudomonas reduced to 18.8 % in day 7 whereas Klebsiella pneumonia and Acinetobacter remained almost same from day 0 to day 7. CONCLUSIONS This study concludes the predominant pathogen as Pseudomonas aeruginosa with sensitivity to imipenem followed by Klebsiella with sensitivity to teicoplanin, vancomycin, amikacin, cefoperazone/tazobactam, linezolid and piperacillin/tazobactam on day 0 with reduction in the number of organisms on day 7 due to the fact that all our patients were admitted in ICU several days prior to tracheostomy and were started on antibiotics soon after admission as per choice of the treating physician. Hence, a clear understanding of bacterial colonisation post tracheostomy and its change in course is essential for timely intervention with empirical antibiotics for reducing the incidence of lower respiratory tract infections after tracheostomy in future. KEY WORDS Tracheostomy, Lower Respiratory Tract Infections, Pseudomonas Aeruginosa, Empirical Antibiotics.

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In Vitro Activity of AR-709 against Streptococcus pneumoniae

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01332-07 ◽

2008 ◽

Vol 52 (3) ◽

pp. 1182-1183 ◽

Cited By ~ 5

Author(s):

W. T. M. Jansen ◽

A. Verel ◽

J. Verhoef ◽

D. Milatovic

Keyword(s):

Streptococcus Pneumoniae ◽

Lower Respiratory Tract ◽

Respiratory Tract Infections ◽

Multidrug Resistant ◽

Vitro Activity ◽

In Vitro Activity ◽

Lower Respiratory Tract Infections ◽

Excellent Activity ◽

Tract Infections

ABSTRACT We investigated the in vitro activity of AR-709, a novel diaminopyrimidine antibiotic currently in development for treatment of community-acquired upper and lower respiratory tract infections, against 151 Streptococcus pneumoniae strains from various European countries. AR-709 showed excellent activity against both drug-susceptible and multidrug-resistant pneumococci.

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