Successful prolonged cefiderocol treatment of a chronic left pleural empyema caused by Pseudomonas aeruginosa in a patient affected by COVID-19: a case report.
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ABSTRACT:
SUBMITTER: Borghesi L
PROVIDER: S-EPMC8455353 | biostudies-literature | 2021 Dec
REPOSITORIES: biostudies-literature
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Successful prolonged cefiderocol treatment of a chronic left pleural empyema caused by Pseudomonas aeruginosa in a patient affected by COVID-19: a case report.
Borghesi Luca L Viaggi Valentina V Franzetti Marco M Montoli Matteo M Mauri Carola C Moioli Giovanni G Benvenuti Mauro Roberto MR Piconi Stefania S Luzzaro Francesco F
Journal of global antimicrobial resistance 20210922
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Project description:BackgroundMany community-acquired pleural infections are caused by facultative and anaerobic bacteria from the human oral microbiota. The epidemiology, clinical characteristics, pathogenesis and etiology of such infections are little studied.The aim of the present prospective multicenter cohort study was to provide a thorough microbiological and clinical characterization of such oral-type pleural infections, and to improve our understanding of the underlying etiology and associated risk factors.MethodsOver a 2-year period, we included 77 patients with community-acquired pleural infection, whereof 63 (82%) represented oral-type pleural infections. Clinical and anamnestic data were systematically collected, and patients were offered a dental assessment by an oral surgeon. Microbial characterizations were done using next-generation sequencing. Obtained bacterial profiles were compared to microbiology data from previous investigations on odontogenic infections, bacteremia after extraction of infected teeth, and community-acquired brain abscesses.ResultsFrom the oral-type pleural infections, we made 267 bacterial identifications representing 89 different species. Streptococcus intermedius and/or Fusobacterium nucleatum were identified as a dominant component in all infections. We found a high prevalence of dental infections among patients with oral-type pleural infection and demonstrate substantial similarities between the microbiology of such pleural infections and that of odontogenic infections, odontogenic bacteremia and community-acquired brain abscesses.ConclusionOral-type pleural infection is the most common type of community-acquired pleural infection. Current evidence supports hematogenous seeding of bacteria from a dental focus as the most important underlying etiology. Streptococcus intermedius and Fusobacterium nucleatum most likely represent key pathogens necessary for establishing the infection.
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Project description:We report a 59-year-old male with left leg osteomyelitis caused by an XDR Pseudomonas aeruginosa strain following a road traffic accident. Limited treatment options and adverse antimicrobial reaction led to consideration of cefiderocol together with appropriate surgical intervention. Improved bony remodelling over the tibia and fibula was observed with good bony alignment and no adverse features. Physiotherapy support was continued for 4 months following treatment, which resulted in good functional mobility, improved proprioception and full ability to bear weight. This case also adds to multiple reports that describe safe and successful use of cefiderocol to treat MDR, aerobic Gram-negative infections.
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Project description:BackgroundMutations in the AmpC-AmpR region are associated with treatment-emergent ceftolozane-tazobactam (TOL-TAZ) and ceftazidime-avibactam (CAZ-AVI) resistance. We sought to determine if these mutations impact susceptibility to the novel cephalosporin-siderophore compound cefiderocol.MethodsThirty-two paired isolates from 16 patients with index P. aeruginosa isolates susceptible to TOL-TAZ and subsequent P. aeruginosa isolates available after TOL-TAZ exposure from January 2019 to December 2020 were included. TOL-TAZ, CAZ-AVI, imipenem-relebactam (IMI-REL), and cefiderocol minimum inhibitory concentrations (MICs) were determined using broth microdilution. Whole-genome sequencing of paired isolates was used to identify mechanisms of resistance to cefiderocol that emerged, focusing on putative mechanisms of resistance to cefiderocol or earlier siderophore-antibiotic conjugates based on the previously published literature.ResultsAnalyzing the 16 pairs of P. aeruginosa isolates, ≥4-fold increases in cefiderocol MICs occurred in 4 of 16 isolates. Cefiderocol nonsusceptibility criteria were met for only 1 of the 4 isolates, using Clinical and Laboratory Standards Institute criteria. Specific mechanisms identified included the following: AmpC E247K (2 isolates), MexR A66V and L57D (1 isolate each), and AmpD G116D (1 isolate) substitutions. For both isolates with AmpC E247K mutations, ≥4-fold MIC increases occurred for both TOL-TAZ and CAZ-AVI, while a ≥4-fold reduction in IMI-REL MICs was observed.ConclusionsOur findings suggest that alterations in the target binding sites of P. aeruginosa-derived AmpC β-lactamases have the potential to reduce the activity of 3 of 4 novel β-lactams (ie, ceftolozane-tazobactam, ceftazidime-avibactam, and cefiderocol) and potentially increase susceptibility to imipenem-relebactam. These findings are in need of validation in a larger cohort.
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Project description:There is considerable interest in the use of bacteriophages (phages) to treat Pseudomonas aeruginosa infections associated with left ventricular assist devices (LVADs). These infections are often challenging to manage due to high rates of multidrug resistance and biofilm formation, which could potentially be overcome with the use of phages. We report a case of a 54-year-old man with relapsing multidrug-resistant P. aeruginosa LVAD driveline infection, who was treated with a combination of two lytic antipseudomonal phages administered intravenously and locally. Treatment was combined with LVAD driveline repositioning and systemic antibiotic administration, resulting in a successful outcome with clinical cure and eradication of the targeted bacteria. However, laboratory in vitro models showed that phages alone could not eradicate biofilms but could prevent biofilm formation. Phage-resistant bacterial strains evolved in biofilm models and showed decreased susceptibility to the phages used. Further studies are needed to understand the complexity of phage resistance and the interaction of phages and antibiotics. Our results indicate that the combination of phages, antibiotics, and surgical intervention can have great potential in treating LVAD-associated infections. More than 21 months post-treatment, our patient remains cured of the infection.
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