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Ceftolozane-Tazobactam Treatment of Hypervirulent Multidrug Resistant Pseudomonas aeruginosa Infections in Neutropenic Patients.

ABSTRACT: The effectiveness of ceftolozane/tazobactam for the treatment of infections in neutropenic patients caused by hypervirulent multidrug-resistant (MDR) Pseudomonas aeruginosa has not been previously reported. We identified seven cases of MDR P. aeruginosa infection in neutropenic patients over a four-month period within the same hematology ward. Four cases were associated with rapid progression despite piperacillin-tazobactam or meropenem therapy, and three patients developed sepsis or extensive skin/soft tissue necrosis. In three of the four cases, patients were empirically switched from meropenem to ceftolozane/avibactam before carbapenem susceptibility test results were available, and all four patients underwent extensive surgical debridement or amputation of affected tissues and survived. Further investigation revealed a common bathroom source of MDR P. aeruginosa clonal subtypes ST175 and ST235 that harbored genes for type III secretion system expression and elaboration of ExoU or ExoS exotoxin. We conclude that ceftolozane/tazobactam plus early source control was critical for control of rapidly progressing skin and soft infection in these neutropenic patients caused by highly virulent ST175 and ST235 clones of MDR P. aeruginosa.

SUBMITTER: Coppola PE

PROVIDER: S-EPMC7767535 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Ceftolozane-Tazobactam Treatment of Hypervirulent Multidrug Resistant Pseudomonas aeruginosa Infections in Neutropenic Patients.

Coppola Paolo E PE Gaibani Paolo P Sartor Chiara C Ambretti Simone S Lewis Russell E RE Sassi Claudia C Pignatti Marco M Paolini Stefania S Curti Antonio A Castagnetti Fausto F Ursi Margherita M Cavo Michele M Stanzani Marta M

Microorganisms 20201221 12

The effectiveness of ceftolozane/tazobactam for the treatment of infections in neutropenic patients caused by hypervirulent multidrug-resistant (MDR) Pseudomonas aeruginosa has not been previously reported. We identified seven cases of MDR P. aeruginosa infection in neutropenic patients over a four-month period within the same hematology ward. Four cases were associated with rapid progression despite piperacillin-tazobactam or meropenem therapy, and three patients developed sepsis ...[more]

PMID: 33371496

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Project description:Multidrug-resistant (MDR) Pseudomonas aeruginosa increasingly causes health care-associated infections. In this study, we determined the activity of ceftolozane-tazobactam, ceftazidime-avibactam, and cefiderocol against 223 MDR P. aeruginosa clinical isolates recovered from 2013 to 2017 at the University Hospital Frankfurt by using MIC test strips. Furthermore, we evaluated the presence of genes encoding major β-lactamases, such as VIM, IMP, NDM, GIM, SPM, and KPC; the extended spectrum β-lactamase (ESBL)-carbapenemase GES; and the virulence-associated traits ExoS and ExoU, as in particular ExoU is thought to be associated with poor clinical outcome. For MDR P. aeruginosa isolates, the MIC50/MIC90 values of ceftolozane-tazobactam, ceftazidime-avibactam, and cefiderocol were 8/>256 mg/L, 16/>256 mg/L, and 0.25/1 mg/L, respectively. Cefiderocol showed the highest susceptibility rate (97.3%) followed by ceftazidime-avibactam (48.4%) and ceftolozane-tazobactam (46.6%). In 81 (36.3%) isolates, carbapenemase gene blaVIM was detected, and in 5 (2.2%) isolates, blaGES was detected (with a positive association of exoU and blaVIM). More than half of the isolates belong to the so-called international P. aeruginosa "high-risk" clones, with sequence type 235 (ST235) (24.7%) being the most prevalent. This study underlines that ceftolozane-tazobactam, ceftazidime-avibactam, and cefiderocol are important options for the treatment of infections due to MDR P. aeruginosa, with cefiderocol currently being the most active available antipseudomonal β-lactam agent. According to our clinical experience, the outcome of cefiderocol therapy (8 patients) was favorable especially in cases of MDR P. aeruginosa-associated complicated urinary tract infections. IMPORTANCE After testing ceftolozane-tazobactam, ceftazidime-avibactam, and cefiderocol against a collection of 233 multidrug-resistant (MDR) Pseudomonas aeruginosa, we showed that cefiderocol is the most active antipseudomonal β-lactam agent (susceptibility rates were 46.6%, 48.4%, and 97.4%, respectively). The most prevalent one was sequence type 235 (ST235) (24.7%), followed by ST244, ST175, and ST233, with all belonging to the top 10 P. aeruginosa high-risk clones with worldwide distribution. Our data indicate that during surveillance studies special attention should be paid to the MDR and highly virulent VIM- and ExoU-producing variant of ST235. Furthermore, in the case of infections caused by carbapenemase-producing MDR P. aeruginosa, cefiderocol is the preferred treatment option, while outcomes of complicated urinary tract infections and hospital-acquired pneumonia with cefiderocol were favorable.

Project description:BackgroundCombination therapy with tazobactam/ceftolozane (TAZ/CTLZ) and high-dose aminoglycosides has been reported to be efficacious in extensively drug-resistant (XDR)-Pseudomonas aeruginosa infection. However, there are no reports of efficacy in XDR-P. aeruginosa infection for combination therapy with low-dose aminoglycosides and TAZ/CTLZ. Herein, we describe a rare case of severe burn injury patients with persistent bacteremia due to XDR-P. aeruginosa, which was successfully treated with TAZ/CTLZ and low-dose tobramycin (TOB).Case presentationA 31-year-old man was admitted to the intensive care unit with severe burn injury involving 52% of the total body surface area and a prognostic burn index of 79.5. The patient had recurrent bacterial infections since admission, and blood cultures collected on the 37th day of admission revealed the presence of P. aeruginosa strains that were resistant to all β-lactams and amikacin (AMK). The results of the antimicrobial synergistic study showed no synergistic effect of low-dose meropenem (MEPM) and AMK combination therapy. The patient had acute renal failure, and it was difficult to increase the dose of MEPM and AMK, respectively. Thus, we initiated TAZ/CTLZ 1.5 g/8 h instead of the AMK and MEPM combination therapy on the 43rd day of hospitalization. Low-dose TAZ/CTLZ was continued because of prolonged renal dysfunction and resulted in a transient clinical improvement. However, the dosage of TAZ/CTLZ could be increased as the renal function improved, but despite an increased TAZ/CTLZ dose, bacteremia persisted, and the blood cultures remained positive. Thus, TOB was added to TAZ/CTLZ at low doses for synergistic effect against Gram-negative bacteria. Blood cultures collected after initiation of combination therapy with TAZ/CTLZ and low-dose TOB were negative on two consecutive follow-up evaluations. Thereafter, although the patient had several episodes of fever and increased inflammatory response, blood cultures consistently tested negative, and all of the wounds healed. On the 93rd day, due to the good healing progress, the patient was transferred to another hospital.ConclusionsTAZ/CTLZ and low-dose TOB combination therapy showed the potential for synergistic effects. Our present report suggests a novel synergistic treatment strategy for rare cases that are refractory to the treatment of infections, such as XDR-P. aeruginosa infection.

Dataset Information

Ceftolozane-Tazobactam Treatment of Hypervirulent Multidrug Resistant Pseudomonas aeruginosa Infections in Neutropenic Patients.

Publications

Ceftolozane-Tazobactam Treatment of Hypervirulent Multidrug Resistant <i>Pseudomonas aeruginosa</i> Infections in Neutropenic Patients.

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