Alcaligenes faecalis metallo-β-lactamase in extensively drug-resistant Pseudomonas aeruginosa isolates

Abstract Background Multidrug-resistant (MDR) and extensively drug-resistant (XDR) Pseudomonas aeruginosa (PA) have limited therapeutic options for treatment. Ceftolozane/tazobactam is a newer anti-pseudomonal drug effective against resistant PA infections, however resistance against this drug has now also developed and is increasing. In this study, we explored the combination of ceftolozane/tazobactam (CT) and meropenem (MP) as a possible effective regimen against MDR and XDR PA. Methods We obtained 33 non-duplicate isolates of MDR and XDR PA grown from blood, urine and respiratory samples collected from patients admitted between 2015 and 2019 at our two affiliate teaching hospitals. MDR PA was defined as resistance to 3 or more classes of anti-pseudomonal antibiotics, and XDR PA as resistance to all but two or less classes of anti-pseudomonal antibiotics. Antimicrobial preparations of both MP and CT were made according to manufacturer instructions. Susceptibility testing was performed using the checkerboard method in accordance to CLSI guidelines (CLSI M100, 2017). The ATCC 27853 strain of PA used as control. Synergy, additive effect, indifference and antagonism were defined as FIC (fractional inhibitory concentration) indices of ≤0.5, >0.5 to <1, >1 to <4, and >4, respectively. Results Thirteen (39%) of 33 PA isolates were classified as XDR, while 20 (61%) PA isolates were MDR. All isolates were resistant to MP (MIC50 >32 ug/mL), while only 2 (6%) isolates were susceptible to CT (MIC50 64 ug/mL). A synergistic effect was seen in 9 (27.3%) of PA isolates (FIC index range 0.28 to 0.5)— 2 of which were XDR PA, and 7 were MDR PA. An additive effect was seen in 12 (36.4%), with indifference seen in 12 (36.4%) of isolates. In this study, no antagonism was seen when CT and MP were combined. Conclusion When used in combination, CT and MP can exert a synergistic effect against MDR and XDR PA. Additive effect and indifference can also be seen when both antibiotics were used. Moreover, there was no antagonism seen when both antibiotics were combined. This study shows that the use of CT and MP in combination may be an option against XDR and MDR PA infections. Disclosures All Authors: No reported disclosures

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Genomic analysis of an extensively drug-resistant Pseudomonas aeruginosa ST312 harbouring IncU plasmid-mediated blaKPC-2 isolated from ascitic fluid

Journal of Global Antimicrobial Resistance ◽

10.1016/j.jgar.2021.03.012 ◽

2021 ◽

Vol 25 ◽

pp. 151-153

Author(s):

Daniela Cristina Tartari ◽

Caetana Paes Zamparette ◽

Graciele Martini ◽

Sandra Christakis ◽

Luiz Henrique Costa ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Ascitic Fluid ◽

Genomic Analysis ◽

Drug Resistant ◽

Extensively Drug Resistant

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Draft Genome Sequence of a Clinically Isolated Extensively Drug-Resistant Pseudomonas aeruginosa Strain

Genome Announcements ◽

10.1128/genomea.00162-16 ◽

2016 ◽

Vol 4 (2) ◽

Author(s):

Bhavani Manivannan ◽

Niranjana Mahalingam ◽

Sudhir Jadhao ◽

Amrita Mishra ◽

Pravin Nilawe ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Antibiotic Resistance ◽

Genome Assembly ◽

Biofilm Formation ◽

Draft Genome ◽

Drug Resistant ◽

Draft Genome Assembly ◽

Extensively Drug Resistant ◽

History Of ◽

Urinary Tuberculosis

We present the draft genome assembly of an extensively drug-resistant (XDR) Pseudomonas aeruginosa strain isolated from a patient with a history of genito urinary tuberculosis. The draft genome is 7,022,546 bp with a G+C content of 65.48%. It carries 7 phage genomes, genes for quorum sensing, biofilm formation, virulence, and antibiotic resistance.

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Extensively drug-resistant Pseudomonas aeruginosa: risk of bloodstream infection in hospitalized patients

European Journal of Clinical Microbiology & Infectious Diseases ◽

10.1007/s10096-012-1629-3 ◽

2012 ◽

Vol 31 (10) ◽

pp. 2791-2797 ◽

Cited By ~ 22

Author(s):

C. Peña ◽

S. Gómez-Zorrilla ◽

C. Suarez ◽

M. A. Dominguez ◽

F. Tubau ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Bloodstream Infection ◽

Hospitalized Patients ◽

Drug Resistant ◽

Extensively Drug Resistant

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Antimicrobial Activity of Ceftazidime-Avibactam Tested against Multidrug-Resistant Enterobacteriaceae and Pseudomonas aeruginosa Isolates from U.S. Medical Centers, 2013 to 2016

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01045-17 ◽

2017 ◽

Vol 61 (11) ◽

Cited By ~ 52

Author(s):

Helio S. Sader ◽

Mariana Castanheira ◽

Dee Shortridge ◽

Rodrigo E. Mendes ◽

Robert K. Flamm

Keyword(s):

Pseudomonas Aeruginosa ◽

Multidrug Resistant ◽

Drug Resistant ◽

Large Collection ◽

Content Type ◽

Negative Results ◽

Medical Centers ◽

Extensively Drug Resistant ◽

Genes Encoding

ABSTRACT The in vitro activity of ceftazidime-avibactam and many comparator agents was determined against various resistant subsets of organisms selected among 36,380 Enterobacteriaceae and 7,868 Pseudomonas aeruginosa isolates. The isolates were consecutively collected from 94 U.S. hospitals, and all isolates were tested for susceptibility by reference broth microdilution methods in a central monitoring laboratory (JMI Laboratories). Enterobacteriaceae isolates resistant to carbapenems (CRE) and/or ceftazidime-avibactam (MIC ≥ 16 μg/ml) were evaluated for the presence of genes encoding extended-spectrum β-lactamases and carbapenemases. Ceftazidime-avibactam inhibited >99.9% of all Enterobacteriaceae at the susceptible breakpoint of ≤8 μg/ml and was active against multidrug-resistant (MDR; n = 2,953; MIC50/90, 0.25/1 μg/ml; 99.2% susceptible), extensively drug-resistant (XDR; n = 448; MIC50/90, 0.5/2 μg/ml; 97.8% susceptible), and CRE (n = 513; MIC50/90, 0.5/2 μg/ml; 97.5% susceptible) isolates. Only 82.2% of MDR Enterobacteriaceae (n = 2,953) and 64.2% of ceftriaxone-nonsusceptible Klebsiella pneumoniae (n = 1,063) isolates were meropenem susceptible. Among Enterobacter cloacae (22.2% ceftazidime nonsusceptible), 99.8% of the isolates, including 99.3% of the ceftazidime-nonsusceptible isolates, were ceftazidime-avibactam susceptible. Only 23 of 36,380 Enterobacteriaceae (0.06%) isolates were ceftazidime-avibactam nonsusceptible, including 9 metallo-β-lactamase producers and 2 KPC-producing strains with porin alteration; the remaining 12 strains showed negative results for all β-lactamases tested. Ceftazidime-avibactam showed potent activity against P. aeruginosa (MIC50/90, 2/4 μg/ml; 97.1% susceptible), including MDR (MIC50/90, 4/16 μg/ml; 86.5% susceptible) isolates, and inhibited 71.8% of isolates nonsusceptible to meropenem, piperacillin-tazobactam, and ceftazidime (n = 628). In summary, ceftazidime-avibactam demonstrated potent activity against a large collection (n = 44,248) of contemporary Gram-negative bacilli isolated from U.S. patients, including organisms resistant to most currently available agents, such as CRE and meropenem-nonsusceptible P. aeruginosa.

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Evaluation of ceftazidime/avibactam for serious infections due to multidrug-resistant and extensively drug-resistant Pseudomonas aeruginosa

Journal of Global Antimicrobial Resistance ◽

10.1016/j.jgar.2018.07.010 ◽

2018 ◽

Vol 15 ◽

pp. 136-139 ◽

Cited By ~ 14

Author(s):

Olga Rodríguez-Núñez ◽

Marco Ripa ◽

Laura Morata ◽

Cristina de la Calle ◽

Celia Cardozo ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Multidrug Resistant ◽

Drug Resistant ◽

Extensively Drug Resistant ◽

Serious Infections

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Extensively drug-resistant Alcaligenes faecalis infection

10.21203/rs.3.rs-27777/v4 ◽

2020 ◽

Author(s):

Chienhsiu Huang

Keyword(s):

Bacterial Infections ◽

Opportunistic Infections ◽

Clinical Symptoms ◽

Clinical Care ◽

Alcaligenes Faecalis ◽

Drug Resistant ◽

Extensively Drug Resistant ◽

Intravenous Antibiotics ◽

Sensitivity Rate ◽

Antibiotics Sensitivity

Abstract Background: Alcaligenes faecalis is usually causes opportunistic infections in humans. Alcaligenes faecalis infection is often difficult to treat due to its increased resistance to several antibiotics. The results from a clinical study of patients with Alcaligenes faecalis infection may help improve patients’ clinical care. Methods: We conducted a retrospective analysis of all patients presenting with Alcaligenes faecalis infection from January 2014 to December 2019. The medical records of all patients were reviewed for demographic information, clinical symptoms and signs, comorbidities, use of intravenous antibiotics within the past three months, bacterial culture, antibiotics sensitivity test, and clinical outcomes. Results: Sixty-one cases of Alcaligenes faecalis infection were seen during the study period, including 25 cases of cystitis, nine cases of diabetic foot infection, eight cases of pneumonia, seven cases of acute pyelonephritis, three cases of bacteremia, and nine cases of infection at specific sites. Thirty-seven patients (60.7%) had a history of receiving intravenous antibiotics within three months of the diagnosis. Fifty-one (83.6%) cases were mixed with other bacterial infections. Extensively drug-resistant infections have been reported since 2018. The best sensitivity rate to A. faecalis was 66.7% for three antibiotics (imipenem, meropenem, and ceftazidime) in 2019. Two antibiotics (ciprofloxacin and piperacillin/tazobactam) sensitivity rates to A. faecalis were less than 50%. Conclusions: The most frequent Alcaligenes faecalis infection sites, in order, are the bloodstream, urinary tract, skin and soft tissue, and middle ear. The susceptibility rate of Alcaligenes faecalis to commonly used antibiotics is decreasing. Extensively drug-resistant Alcaligenes faecalis infections have emerged.

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Extensively Drug-Resistant Pseudomonas aeruginosa ST309 Harboring Tandem Guiana Extended Spectrum β-Lactamase Enzymes: A Newly Emerging Threat in the United States

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz273 ◽

2019 ◽

Vol 6 (7) ◽

Cited By ~ 12

Author(s):

Ayesha Khan ◽

Truc T Tran ◽

Rafael Rios ◽

Blake Hanson ◽

William C Shropshire ◽

...

Keyword(s):

United States ◽

Pseudomonas Aeruginosa ◽

Phylogenetic Analysis ◽

The United States ◽

Clinical Isolates ◽

Drug Resistant ◽

Class 1 Integron ◽

E Coli ◽

Extensively Drug Resistant ◽

Extended Spectrum

Abstract Background Treatment of serious infections due to multidrug-resistant (MDR) Pseudomonas aeruginosa remains a challenge, despite the introduction of novel therapeutics. In this study, we report 2 extensively drug-resistant clinical isolates of sequence type (ST) 309 P aeruginosa resistant to all β-lactams, including the novel combinations ceftolozane/tazobactam, ceftazidime/avibactam, and meropenem/vaborbactam. Methods Isolates were sequenced using both short-read (Illumina) and long-read technology to identify resistance determinants, polymorphisms (compared with P aeruginosa PAO1), and reconstruct a phylogenetic tree. A pair of β-lactamases, Guiana extended spectrum β-lactamase (GES)-19 and GES-26, were cloned and expressed in a laboratory strain of Escherichia coli to examine their relative impact on resistance. Using cell lysates from E coli expressing the GES genes individually and in tandem, we determined relative rates of hydrolysis for nitrocefin and ceftazidime. Results Two ST309 P aeruginosa clinical isolates were found to harbor the extended spectrum β-lactamases GES-19 and GES-26 clustered in tandem on a chromosomal class 1 integron. The presence of both enzymes in E coli was associated with significantly elevated minimum inhibitory concentrations to aztreonam, cefepime, meropenem, ceftazidime/avibactam, and ceftolozane/tazobactam, compared with those expressed individually. The combination of ceftazidime/avibactam plus aztreonam was active in vitro and used to achieve cure in one patient. Phylogenetic analysis revealed ST309 P aeruginosa are closely related to MDR strains from Mexico also carrying tandem GES. Conclusions The presence of tandem GES-19 and GES-26 is associated with resistance to all β-lactams, including ceftolozane/tazobactam. Phylogenetic analysis suggests that ST309 P aeruginosa may be an emerging threat in the United States.

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