Dataset Information

Combination of phage therapy and cefiderocol to successfully treat Pseudomonas aeruginosa cranial osteomyelitis.

ABSTRACT:

Background

Pseudomonas aeruginosa has the ability to exhibit resistance to a broad range of antibiotics, highlighting the importance of identifying alternative or adjunctive treatment options, such as phages.

Patients and methods

We report the case of a 25-year-old male who experienced an accidental electrocution resulting in exposed calvarium in the left parieto-temporal region, complicated by a difficult-to-treat P. aeruginosa (DTR-P. aeruginosa) infection. Cefiderocol was the sole antibiotic with consistent activity against six bacterial isolates obtained from the infected region over a 38 day period.

Results

WGS analysis identified a bla _GES-1 gene as well as the MDR efflux pumps MexD and MexX in all six of the patient's ST235 DTR-P. aeruginosa isolates, when compared with the reference genome P. aeruginosa PA01 and a P. aeruginosa ST235 isolate from an unrelated patient. After debridement of infected scalp and bone, the patient received approximately 6 weeks of cefiderocol in conjunction with IV phage Pa14NPøPASA16. Some improvement was observed after the initiation of cefiderocol; however, sustained local site improvement and haemodynamic stability were not achieved until phage was administered. No medication-related toxicities were observed. The patient remains infection free more than 12 months after completion of therapy.

Conclusions

This report adds to the growing literature that phage therapy may be a safe and effective approach to augment antibiotic therapy for patients infected with drug-resistant pathogens. Furthermore, it highlights the importance of the GES β-lactamase family in contributing to inactivation of a broad range of β-lactam antibiotics in P. aeruginosa, including ceftolozane/tazobactam, ceftazidime/avibactam and imipenem/relebactam.

SUBMITTER: Simner PJ

PROVIDER: S-EPMC9071546 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

Combination of phage therapy and cefiderocol to successfully treat <i>Pseudomonas aeruginosa</i> cranial osteomyelitis.

Simner Patricia J PJ Cherian Jerald J Suh Gina A GA Bergman Yehudit Y Beisken Stephan S Fackler Joseph J Lee Martin M Hopkins Robert J RJ Tamma Pranita D PD

JAC-antimicrobial resistance 20220505 3

<h4>Background</h4><i>Pseudomonas aeruginosa</i> has the ability to exhibit resistance to a broad range of antibiotics, highlighting the importance of identifying alternative or adjunctive treatment options, such as phages.<h4>Patients and methods</h4>We report the case of a 25-year-old male who experienced an accidental electrocution resulting in exposed calvarium in the left parieto-temporal region, complicated by a difficult-to-treat <i>P. aeruginosa</i> (DTR-<i>P. aeruginosa</i>) infection. ...[more]

PMID: 35529052

Similar Datasets

Project description:High-energy trauma with severe bone fractures can be complicated by infection, leading to the development of osteomyelitis. Pseudomonas aeruginosa is an important causative agent of such infections because of its high virulence profile and ability to develop resistance against a wide range of antimicrobials quickly. P. aeruginosa biofilms cause treatment failure and relapsing infections. Bacteriophages are viruses that can be used to treat biofilm-associated infections. Moreover, the combination of phages with certain antimicrobials have demonstrated synergistic and additive effects. We present a case of a 21-year-old patient with relapsing multidrug-resistant (MDR) P. aeruginosa femur osteomyelitis that developed after a road accident, with a proximal right femoral Grade III B open fracture and severe soft tissue damage. Despite extensive antimicrobial treatment and multiple surgical interventions with wound debridement, the infection persisted, with subsequent development of femoral osteomyelitis with a fistula. Patient care management included femoral head excision with wound debridement, intravenous (IV) ceftazidime-avibactam, and the local application of the lytic Pseudomonas bacteriophage cocktail BFC 1.10. Nine months after the intervention, the patient did not show any clinical, radiological, or laboratory signs of inflammation; therefore, hip replacement was performed. Nevertheless, recurrent P. aeruginosa infection evolved at the distal side of the femur and was successfully treated with conventional antimicrobials. In this case, wound debridement combined with antibiotics and bacteriophages resulted in bacterial eradication of proximal femoral segment, avoiding leg amputation, but failed to treat osteomyelitis in distal bone segment. An in vitro assessment of the isolated MDR P. aeruginosa strain for biofilm formation and phage susceptibility was performed. Additionally, the antimicrobial effects of ceftazidime-avibactam and BFC 1.10 were determined on planktonic cell growth and bacterial biofilm prevention was evaluated. The isolated bacterial strains were susceptible to the bacteriophage cocktail. Strong biofilm formation was detected 6 h after inoculation. Ceftazidime-avibactam combined with BFC 1.10 was most effective in preventing planktonic cell growth and biofilm formation. In both cases, the required concentration of ceftazidime-avibactam decreased two-fold. This study demonstrates the possible use of bacteriophages and antibiotics in difficult-to-treat bone and soft tissue infections, where the additive effects of phages and antibiotics were observed.