Therapeutic Management of Pseudomonas aeruginosa Bloodstream Infection Non-Susceptible to Carbapenems but Susceptible to “Old” Cephalosporins and/or to Penicillins

Abstract

It is unknown as to whether other beta-lactams can be used for bloodstream infections (BSI) resulting from Pseudomonas aeruginosa (PA) which are non-susceptible to one or more carbapenem. We conducted a retrospective cohort study at the Assaf Harofeh Medical Center (AHMC) from January 2010 to August 2014. Adult patients with PA-BSI non-susceptible to a group 2 carbapenem but susceptible to ceftazidime or piperacillin (with or without tazobactam), were enrolled. We compared the outcomes of patients who received an appropriate beta-lactam antibiotic (“cases”) to those who received an appropriate non-beta-lactam antibiotic (“controls”). Whole genome sequencing was performed for one of the isolates. Twenty-six patients with PA-BSI met inclusion criteria: 18 received a beta-lactam and 8 a non-beta-lactam (three a fluoroquinolone, two colistin, one a fluoroquinolone and an aminoglycoside, one a fluoroquinolone and colistin, and one colistin and an aminoglycoside). All clinical outcomes were similar between the groups. There were large variations in the phenotypic susceptibilities of the strains. A detailed molecular investigation of one isolate revealed a strain that belonged to MLST-137, with the presence of multiple efflux pumps, OXA-50, and a chromosomally mediated Pseudomonas-derived cephalosporinase (PDC). The oprD gene was intact. Non-carbapenem-β-lactams may still be effective alternatives for short duration therapy (up to 14 days) for BSI caused by a carbapenem non-susceptible (but susceptible to ceftazidime, piperacillin, and/or piperacillin-tazobactam) PA strain. This observation requires further confirmatory analyses. Future molecular investigations should be performed, in order to further analyze additional potential mechanisms for this prevalent phenotype.

It’s Not Easy Being Green: A Narrative Review on the Microbiology, Virulence and Therapeutic Prospects of Multidrug-Resistant Pseudomonas aeruginosa

“…Zaidenstein et al reported sixty-seven Car-R/Ceph-S bloodstream infections from monobacterial clinical syndromes over a 5-year period (2010-2014). The authors have noted that in these cases, cephalosporins were considered as relevant therapeutic options [236]. Tsai et al characterized n = 14 P. aeruginosa isolates, that were resistant to carbapenems only.…”

“…Even though there is growing literature available on the topic, there is no consensus on the most common mechanisms of resistance contributing to the emergence of Car-R/Ceph-S isolates. There are wide-ranging differences in the prevalence of carbapenemases (especially for MBLs), and this may affect the susceptibility to cephalosporins as well [73,[230][231][232][233][234][235][236][237][238][239][240][241][242][243][244]. Khalili et al proposed that the detection of Car-R/Ceph-S isolates is dependent on the absence of carbapenemases [240].…”

Carbapenem-Resistant but Cephalosporin-Susceptible Pseudomonas aeruginosa in Urinary Tract Infections: Opportunity for Colistin Sparing

“…Most of these bacteria had reduced oprD gene expression levels, while AmpC hyperproduction, carbapenem hydrolysis (detected by the MALDI-TOF MS method) and efflux pump overexpression (RT-PCR) were not shown in these isolates. A recently published clinical study from Israel (corresponding to the time period between 2010 and 2014) reported n = 67 monobacterial Car-R/Ceph-S bloodstream infections (mainly associated with UTIs and pneumonia), where the authors highlighted that cephalosporins were relevant therapeutic options for these infections [31]. In addition, a study from Iran identified n = 23 Car-R/Ceph-S P. aeruginosa isolates from 243 clinical samples, from the time period between 2016 and 2018 [14].…”

Phenotypic and Genotypic Characteristics of Pseudomonas aeruginosa Causing Bloodstream Infection from Six Tertiary Hospitals in Beijing, China

“…Thus, clinicians may consider the use of ceftazidime, cefepime, or piperacillin-tazobactam against these P. aeruginosa isolates. Some studies suggested that non-carbapenem-beta-lactams (ceftazidime, piperacillin, and/or piperacillin-tazobactam) may still be effective alternatives for short-course therapy for BSI caused by P. aeruginosa strains, but should be used with caution in high-inoculum infections such as endocarditis and osteomyelitis [11,12].…”