key: cord-0962858-kebg0p6q
authors: Borghesi, Luca; Viaggi, Valentina; Franzetti, Marco; Montoli, Matteo; Mauri, Carola; Moioli, Giovanni; Benvenuti, Mauro Roberto; Piconi, Stefania; Luzzaro, Francesco
title: Successful prolonged cefiderocol treatment of a chronic left pleural empyema caused by Pseudomonas aeruginosa in a patient affected by COVID-19: a case report
date: 2021-09-22
journal: J Glob Antimicrob Resist
DOI: 10.1016/j.jgar.2021.09.005
sha: 8de4567c0b3686bc0ceb66d53b58a3e64be109c2
doc_id: 962858
cord_uid: kebg0p6q

nan

Infections due to multidrug-resistant (MDR) bacteria pose an increasing therapeutic challenge, often requiring the use of newly introduced antibiotics. A further criticism is now represented by the overcoming clinical and epidemiological challenge of COVID-19. With regard to infections caused by Gram-negative microorganisms, new potentially-active drugs (e.g., cefiderocol, ceftolozane/tazobactam, ceftazidime/avibactam, and meropenem/vaborbactam) have enriched the antimicrobial armamentarium but some concern remains about the treatment of infections caused by isolates having specific resistance mechanisms such as metallo-beta-lactamase production, porin loss and increased efflux pump activity. In the case of Pseudomonas aeruginosa all these resistance mechanisms may be expressed, also simultaneously, thus determining difficult-to-treat infections.

Here, we report on the case of a 64-year-old man suffering from a chronic left pleural empyema caused by a carbapenem-resistant P. aeruginosa (imipenem and meropenem MICs > 8 mg/L) following a pleuropneumectomy surgery carried out in June 2019 after that a mesothelioma was diagnosed. In this context, a thoracostomy drainage was maintained in place for a long period of time to allow the pleural discharge.

On March 2020, the patient noticed an increased discharge from the pleural drainage. At this time, the carbapenem-resistant P. aeruginosa was still detected from the purulent fluid, associated to a low-grade fever. The isolate was also resistant to all beta-lactams and Cefiderocol is a novel parental siderophore cephalosporin with high stability against hydrolysis by all carbapenemases and a peculiar entry into bacterial cells through active iron transporters, independently on porin channels and efflux pumps [1] . Some clinical trials show that cefiderocol may be effective against severe and difficult-to-treat infections.

Few case reports have previously described the successful use of cefiderocol for treating P.

aeruginosa infections in different settings, such as osteomyelitis [2] and surgical site infections [3] , but no conclusive results are available about some questions. For instance, it remains largely unclear whether cefiderocol should be used alone or in combination with other antimicrobials [4] .

Empyema has been described as a possible sanctuary for resistant bacteria, since antibiotics have been proven to reach the site of infection below therapeutic concentrations, thus increasing the risk of resistance emergence [5] . Our experience shows that a combined antibiotic treatment including cefiderocol may be effective for eradicating infection in this setting even though the role of a dedicated surgical procedure remains crucial for treating pleural empyema. It is also noting that in our case prolonged cefiderocol treatment (4 weeks)

was not associated with the presence of significant adverse events.

Cefiderocol: a novel siderophore cephalosporin defeating carbapenemresistant pathogens

Long-term compassionate use of cefiderocol to treat chronic osteomyelitis caused by extensively drug-resistant Pseudomonas aeruginosa and extended-spectrum-β-lactamase-producing Klebsiella pneumoniae in a pediatric patient

Recurrent neurosurgical site infection by extensively drug-resistant P. aeruginosa treated with cefiderocol: a case report and literature review

Evaluating cefiderocol in the treatment of multidrug-resistant Gram-negative bacilli: a review of the emerging data

Cefiderocol for treatment of an empyema due to extensively drug-resistant Pseudomonas aeruginosa: clinical observations and susceptibility testing considerations

Funding: None.Ethical approval: A written consent was obtained by the patient for all the off-label treatments carried out during the stay. For the compassionate use of cefiderocol, the approval of the Hospital Ethics Committee was also received.

C Reactive Protein (CRP), White Blood Cells (WBC) trends and antibiotic treatments during the hospital stay.