Cumulative Antimicrobial Susceptibility Data of Pseudomonas Aeruginosa Isolates from Cystic Fibrosis Patients: 4-Year Experience

Author(s):  
Ebru Fidan ◽  
Gamze Alci ◽  
Seda Sevilay Koldaş ◽  
Bülent Karadag ◽  
Yasemin Gökdemir ◽  
...  

Abstract Objective Pseudomonas aeruginosa is the most important cause of lung infection among cystic fibrosis (CF) patients, and to reduce the severity of the infection, facility-specific cumulative antibiograms could help clinicians in empirical treatment. Methods Respiratory samples of CF patients between January 2015 and December 2018 were scanned through Laboratory Operating System retrospectively. Demographical data of patients, culture results, and antibiotic susceptibilities are recorded using Microsoft Excel 2010. Cumulative antibiogram data were obtained according to the CLSI M39A4 document. Results The number of registered patients has increased in 4 years from 154 to 253. The mean age of patients varied from 9 to 11.7 (range, 2–42). The ratio of patients with a positive culture for P. aeruginosa increased from 32 to 40%, and the mean patients' age decreased from 16.6 to 11.1 (p <0.05). A total number of 4,146 respiratory samples were analyzed. Sputum samples consisted of 42.5% (n: 1,767) of the samples with a 58.4% isolation rate of P. aeruginosa (n: 1,034). A notable increase of resistance was seen almost all antimicrobials tested by years. The ratio of multidrug-resistant (MDR) P. aeruginosa was 4.1, 10.2, 4.5, and 8.6% in 2015, 2016, 2017, and 2018. Conclusion Antimicrobial resistance is a challenging problem in CF patients, and surveillance should be done regularly.

2021 ◽  
Vol 9 (3) ◽  
pp. 478
Author(s):  
Ersilia Vita Fiscarelli ◽  
Martina Rossitto ◽  
Paola Rosati ◽  
Nour Essa ◽  
Valentina Crocetta ◽  
...  

As disease worsens in patients with cystic fibrosis (CF), Pseudomonas aeruginosa (PA) colonizes the lungs, causing pulmonary failure and mortality. Progressively, PA forms typical biofilms, and antibiotic treatments determine multidrug-resistant (MDR) PA strains. To advance new therapies against MDR PA, research has reappraised bacteriophages (phages), viruses naturally infecting bacteria. Because few in vitro studies have tested phages on CF PA biofilms, general reliability remains unclear. This study aimed to test in vitro newly isolated environmental phage activity against PA isolates from patients with CF at Bambino Gesù Children’s Hospital (OBG), Rome, Italy. After testing in vitro phage activities, we combined phages with amikacin, meropenem, and tobramycin against CF PA pre-formed biofilms. We also investigated new emerging morphotypes and bacterial regrowth. We obtained 22 newly isolated phages from various environments, including OBG. In about 94% of 32 CF PA isolates tested, these phages showed in vitro PA lysis. Despite poor efficacy against chronic CF PA, five selected-lytic-phages (Φ4_ZP1, Φ9_ZP2, Φ14_OBG, Φ17_OBG, and Φ19_OBG) showed wide host activity. The Φ4_ZP1-meropenem and Φ14_OBG-tobramycin combinations significantly reduced CF PA biofilms (p < 0.001). To advance potential combined phage-antibiotic therapy, we envisage further in vitro test combinations with newly isolated phages, including those from hospital environments, against CF PA biofilms from early and chronic infections.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S731-S731
Author(s):  
Laura J Rojas ◽  
Mohamad Yasmin ◽  
Jacquelynn Benjamino ◽  
Steven Marshall ◽  
Kailynn DeRonde ◽  
...  

Abstract Background Pseudomonas aeruginosa is a persistent and difficult-to-treat pathogen in many patients, especially those with cystic fibrosis (CF). Herein, we describe our experience managing a young woman suffering from CF with XDR P. aeruginosa who underwent lung transplantation. We highlight the contemporary difficulties reconciling the clinical, microbiological, and genetic information. Methods Mechanism-based-susceptibility disk diffusion synergy testing with double and triple antibiotic combinations aided in choosing tailored antimicrobial combinations to control the infection in the pre-transplant period, create an effective perioperative prophylaxis regimen, and manage recurrent infections in the post-transplant period. Thirty-six sequential XDR and PDR P. aeruginosa isolates obtained from the patient within a 17-month period, before and after a double-lung transplant were analyzed by whole genome sequencing (WGS) and RNAseq in order to understand the genetic basis of the observed resistance phenotypes, establish the genomic population diversity, and define the nature of sequence changes over time Results Our phylogenetic reconstruction demonstrates that these isolates represent a genotypically and phenotypically heterogeneous population. The pattern of mutation accumulation and variation of gene expression suggests that a group of closely related strains was present in the patient prior to transplantation and continued to evolve throughout the course of treatment regardless of antibiotic usage.Our findings challenge antimicrobial stewardship programs that assist with the selection and duration of antibiotic regimens in critically ill and immunocompromised patients based on single-isolate laboratory-derived resistant profiles. We propose that an approach sampling the population of pathogens present in a clinical sample instead of single colonies be applied instead when dealing with XDR P. aeruginosa, especially in patients with CF. Conclusion In complex cases such as this, real-time combination testing and genomic/transcriptomic data could lead to the application of true “precision medicine” by helping clinicians choose the combination antimicrobial therapy most likely to be successful against a population of MDR pathogens present. Disclosures Federico Perez, MD, MS, Accelerate (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support) Robert A. Bonomo, MD, Entasis, Merck, Venatorx (Research Grant or Support)


2015 ◽  
Vol 9 (12) ◽  
pp. 1323-1330 ◽  
Author(s):  
Basima Abdalla Almomani ◽  
Amanda McCullough ◽  
Rawan Gharaibeh ◽  
Shaher Samrah ◽  
Fatimah Mahasneh

Introduction: Ventilator-associated pneumonia (VAP) caused by multidrug-resistant Acinetobacter baumannii (MDR-AB) is common in hospitals and impacts patient survival. We determined the incidence of MDR-AB VAP in critical care units and examined the predictors of 14-day mortality in these patients. Methodology: A retrospective case series study was conducted at a tertiary referral teaching hospital in north Jordan. A list of patients with a positive culture of A. baumannii between January 2007 and June 2013 was retrieved using computerized hospital databases. Medical records of all these patients were reviewed, and cases of VAP infected with MDR-AB were identified. Predictors of 14-day mortality were determined using multivariable logistic regression adjusted for possible confounders. Results: Out of 121 A. baumannii-VAP cases, 119 (98.3%) were caused by MDR-AB. The incidence rate of MDR-AB VAP was 1.59 cases per 100 critical care unit admissions. The mortality of A. baumannii-VAP cases in critical care units was 42% (50/119). Being prescribed two or more definitive antibiotics (prescribed based on susceptibility data) (OR = 0.075, 95% CI = 0.017–0.340, p = 0.001) and ipratropium/salbutamol during mechanical ventilation (OR = 0.140, 95% CI = 0.028–0.705, p = 0.017) were independently associated with lower hospital mortality. Conclusions: Our results suggest incidence of MDR-AB VAP in critical care units is high and that prescription of antibiotics based on antibiotic susceptibility and use of bronchodilators is associated with lower mortality in this population. Larger prospective studies are needed to explore whether these findings can be replicated in different clinical settings.


2020 ◽  
Vol 64 (12) ◽  
Author(s):  
Iris H. Chen ◽  
David P. Nicolau ◽  
Joseph L. Kuti

ABSTRACT Combination therapy may enhance imipenem/cilastatin/relebactam’s (I/R) activity against Pseudomonas aeruginosa and suppress resistance development. Human-simulated unbound plasma concentrations of I/R at 1.25 g every 6 h (h), colistin at 360 mg daily, and amikacin at 25 mg/kg daily were reproduced alone and in combination against six imipenem-nonsusceptible P. aeruginosa isolates in an in vitro pharmacodynamic model over 24 h. For I/R alone, the mean reductions in CFU ± the standard errors by 24 h were −2.52 ± 0.49, −1.49 ± 0.49, −1.15 ± 0.67, and −0.61 ± 0.10 log10 CFU/ml against isolates with MICs of 1/4, 2/4, 4/4, and 8/4 μg/ml, respectively. Amikacin alone also resulted in 24 h CFU reductions consistent with its MIC, while colistin CFU reductions did not differ. Resistant subpopulations were observed after 24 h in 1, 4, and 3 I/R-, colistin-, and amikacin-exposed isolates, respectively. The combination of I/R and colistin resulted in synergistic (n = 1) or additive (n = 2) interactions against three isolates with 24-h CFU reductions ranging from −2.62 to −4.67 log10 CFU/ml. The combination of I/R and amikacin exhibited indifferent interactions against all isolates, with combined drugs achieving −0.51- to −3.33-log10 CFU/ml reductions. No resistant subpopulations were observed during I/R and colistin combination studies, and when added to amikacin, I/R prevented the emergence of amikacin resistance. Against these six multidrug-resistant P. aeruginosa, I/R alone achieved significant CFU reductions against I/R-susceptible isolates. Combinations of I/R plus colistin resulted in additivity or synergy against some P. aeruginosa, whereas the addition of amikacin did not provide further antibacterial efficacy against these isolates.


2014 ◽  
Vol 59 (1) ◽  
pp. 427-436 ◽  
Author(s):  
Veronica N. Kos ◽  
Maxime Déraspe ◽  
Robert E. McLaughlin ◽  
James D. Whiteaker ◽  
Paul H. Roy ◽  
...  

ABSTRACTMany clinical isolates ofPseudomonas aeruginosacause infections that are difficult to eradicate due to their resistance to a wide variety of antibiotics. Key genetic determinants of resistance were identified through genome sequences of 390 clinical isolates ofP. aeruginosa, obtained from diverse geographic locations collected between 2003 and 2012 and were related to microbiological susceptibility data for meropenem, levofloxacin, and amikacin. β-Lactamases and integron cassette arrangements were enriched in the established multidrug-resistant lineages of sequence types ST111 (predominantly O12) and ST235 (O11). This study demonstrates the utility of next-generation sequencing (NGS) in defining relevant resistance elements and highlights the diversity of resistance determinants withinP. aeruginosa. This information is valuable in furthering the design of diagnostics and therapeutics for the treatment ofP. aeruginosainfections.


Thorax ◽  
2019 ◽  
Vol 74 (8) ◽  
pp. 740-748 ◽  
Author(s):  
Sabariah Noor Harun ◽  
Nicholas H G Holford ◽  
Keith Grimwood ◽  
Claire E Wainwright ◽  
Stefanie Hennig

BackgroundWhile Aspergillus detection rates in adults, adolescents and older children with cystic fibrosis (CF) have increased, the risk of acquiring this fungal pathogen in young children is unknown.AimTo determine the risk and explanatory factors of acquiring Aspergillus in children with CF by age 5 years.MethodsCross-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 Aspergillus at age 5 years. A parametric repeated time-to-event model quantitatively described the risk and factors associated with acquiring Aspergillus and Pseudomonas aeruginosa from birth until age 5 years.ResultsCross-sectional analysis found that the number of P. aeruginosa eradication courses increased the odds of detecting Aspergillus at age 5 years (OR 1.61, 95% CI 1.23 to 2.12). The median (IQR) age for the first P. aeruginosa positive culture was 2.38 (1.32–3.79) years and 3.69 (1.68–4.74) years for the first Aspergillus positive culture. The risk of P. aeruginosa and Aspergillus events changes with time after the first year of study entry. It also decreases for P. aeruginosa after completing P. aeruginosa eradication (HR 0.15, 95% CI 0.00 to 0.79), but increases for Aspergillus events (HR 2.75, 95% CI 1.45 to 5.41). The risk of acquiring both types of events increases after having had a previous event.ConclusionIn young children with CF, completing P. aeruginosa eradication therapy and previous Aspergillus events are associated with increased risk of acquiring Aspergillus.


2020 ◽  
Author(s):  
Mazen A. Sid Ahmed ◽  
Faisal Ahmad Khan ◽  
Ali A. Sultan ◽  
Bo Soderquist ◽  
Emad Bashir Ibrahim ◽  
...  

Abstract Background: Anti-pseudomonal b-lactam antibiotics are of paramount importance in the management of Pseudomonas aeruginosa infections. The distribution of b-lactam resistance genes in P. aeruginosa is often closely related to the distribution of certain high-risk international clones. In the present study whole-genome sequencing (WGS) was used to identify the predominant sequence types (STs) and b-lactamase genes in clinical isolates of multidrug-resistant (MDR)-P. aeruginosa from QatarMethods: Microbiological identification and susceptibility tests were performed by automated BD PhoenixTM system and manual Liofilchem MIC Test Strips. Seventy-five MDR-P. aeruginosa isolates were subsequently processed for WGS. Results: Among 75 MDR-P. aeruginosa isolates; the largest proportions of susceptibility were to ceftazidime-avibactam (n=36, 48%), followed by ceftolozane-tazobactam (30, 40%), ceftazidime (n=21, 28%) and aztreonam (n=16, 21.33%). Almost all isolates possessed Class C and Class D b-lactamases (n=72, 96% each), while metallo-β-lactamases were detected in 20 (26.67%) isolates. Eight (40%) metallo-β-lactamases producers were susceptible to aztreonam and did not produce any concomitant extended-spectrum b-lactamases. The most frequent sequence types identified were ST235 (n=16, 21.33%), ST357 (n=8, 10.67%), ST389 and ST1284 (6, 8% each). Nearly all ST235 (15/16; 93.75%) were resistant to all tested b-lactams.Conclusion: MDR-P. aeruginosa isolates from Qatar are highly resistant to antipseudomonal b-lactams. Global high-risk STs are predominant in Qatar and their associated multi-resistant phenotypes are a cause for considerable concern. The molecular epidemiology trends of P. aeruginosa should be surveillance at national levels to track their trends and institute the appropriate control strategies.


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