Browse
Submit Data
Databases
API
Help

Dataset Information

6 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Education: A compassionate use of cefiderocol to treat osteomyelitis caused by an XDR Pseudomonas aeruginosa.

ABSTRACT: 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.

SUBMITTER: Chavda A

PROVIDER: S-EPMC8251337 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

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.

Project description:We report a 15 year-old Nigerian adolescent male with chronic osteomyelitis caused by an extensively drug-resistant (XDR) Pseudomonas aeruginosa strain of sequence type 773 (ST773) carrying blaNDM-1 and an extended spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae strain. The patient developed neurological side effects in the form of circumoral paresthesia with polymyxin B and asymptomatic elevation of transaminases with aztreonam (used in combination with ceftazidime-avibactam). Cefiderocol treatment for 14 weeks plus bone implantation resulted in apparent cure and avoided amputation.

| S-EPMC7179260 | biostudies-literature

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

Project description:BackgroundPseudomonas 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 methodsWe 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.ResultsWGS 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.ConclusionsThis 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.

| S-EPMC9071546 | biostudies-literature

Compassionate use of cefiderocol for carbapenem-resistant Acinetobacter baumannii prosthetic joint infection.

Project description:BackgroundCefiderocol is a recently licensed novel siderophore-conjugated cephalosporin stable to hydrolysis by serine and MBLs. It has been successfully used to treat Enterobacterales infections and is approved for the treatment of infections due to aerobic Gram-negative organisms in adults with limited treatment options.ObjectivesTo describe the compassionate use of cefiderocol and clinical outcome in a case of prosthetic joint infection due to MDR Acinetobacter baumannii.Patients and methodsThis case study follows a 66-year-old woman who sustained an open fracture of the left distal humerus in Pakistan. She underwent open reduction and internal fixation and on return to the UK presented to hospital with a discharging surgical wound.ResultsDebridement of her wound cultured NDM carbapenemase-producing A. baumannii susceptible to colistin, tobramycin and tigecycline only. She developed vomiting with acute kidney injury with colistin and tigecycline. Antimicrobial efficacy of cefiderocol was predicted from in vitro and in vivo susceptibility tests. A successful request was made to Shionogi for compassionate use of cefiderocol, which was added to tigecycline. Cefiderocol was well tolerated with no toxicity and improved renal function. In total she received 25 days of cefiderocol and continued on tigecycline for a further 6 weeks in the community. She has well-healed wounds and good range of elbow movement.ConclusionsCefiderocol's novel mode of cell entry is effective against MDR Gram-negative bacteria with reduced toxicity compared with other last line antibiotics. Our case demonstrates that cefiderocol may be useful as therapy for patients with limited treatment options due to antimicrobial resistance.

| S-EPMC8251250 | biostudies-literature

Potential Use of Dimethyl Sulfoxide in Treatment of Infections Caused by Pseudomonas aeruginosa.

Project description:Dimethyl sulfoxide (DMSO) is commonly used as a solvent to dissolve water-insoluble drugs or other test samples in both in vivo and in vitro experiments. It was observed during our experiment that DMSO at noninhibitory concentrations could significantly inhibit pyocyanin production in the human pathogen Pseudomonas aeruginosa Pyocyanin is an important pathogenic factor whose production is controlled by a cell density-dependent quorum-sensing (QS) system. Investigation of the effect of DMSO on QS showed that DMSO has significant QS antagonistic activities and concentrations of DMSO in the micromolar range attenuated a battery of QS-controlled virulence factors, including rhamnolipid, elastase, and LasA protease production and biofilm formation. Further study indicated that DMSO inhibition of biofilm formation and pyocyanin production was attained by reducing the level of production of an autoinducer molecule of the rhl QS system, N-butanoyl-l-homoserine lactone (C4-HSL). In a mouse model of a burn wound infection with P. aeruginosa, treatment with DMSO significantly decreased mouse mortality compared with that for mice in the control group. The capacity of DMSO to attenuate the pathogenicity of P. aeruginosa points to the potential use of DMSO as an antipathogenic agent for the treatment of P. aeruginosa infection. As a commonly used solvent, however, DMSO's impact on bacterial virulence calls for cautionary attention in its usage in biological, medicinal, and clinical studies.

| S-EPMC5118995 | biostudies-literature

Cefiderocol Activity Against Clinical Pseudomonas aeruginosa Isolates Exhibiting Ceftolozane-Tazobactam Resistance.

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.

| S-EPMC8275882 | biostudies-literature

Ceftolozane-tazobactam and Fosfomycin for rescue treatment of otogenous meningitis caused by XDR Pseudomonas aeruginosa: Case report and review of the literature.

Project description:Extensively drug resistant Pseudomonas aeruginosa (XDR-PA) strains with limited or absent residual antimicrobial susceptibility cause a growing burden of difficult-to treat infections. Treatment options are even more limited for patients with central nervous system (CNS) involvement, as colistin-based regimens are hampered by poor blood brain barrier penetration, being often associated with insufficient clinical and microbiological success. New treatment options are awaited, but evidence from prospective evidence-based evaluations is still lacking. Here we report a case of breakthrough otogenous meningitis caused by XDR-PA in a young patient treated with meropenem and colistin for XDR-PA bloodstream infection and pneumonia after a car-crash polytrauma. The patient was treated with off-label, high-dose ceftolozane-tazobactam and high-dose fosfomycin after characterization of CNS XDR-PA isolates, with rapid clinical and microbiological resolution of meningitis. Our experience, although based on a single case, lands preliminary support to the concept that rescue regimens including ceftolozane-tazobactam and fosfomycin may be considered for XDR-PA CNS infections in patients without alternative therapeutic options.

| S-EPMC6156803 | biostudies-other

Successful prolonged cefiderocol treatment of a chronic left pleural empyema caused by Pseudomonas aeruginosa in a patient affected by COVID-19: a case report.

Project description: Not available

| S-EPMC8455353 | biostudies-literature

Compassionate Use of Avacopan in Difficult-to-Treat Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Project description: Not available

| S-EPMC8897689 | biostudies-literature

Personalized bacteriophage therapy to treat pandrug-resistant spinal Pseudomonas aeruginosa infection.

Project description:Bone and joint infections (BJI) are one of the most difficult-to-treat bacterial infection, especially in the era of antimicrobial resistance. Lytic bacteriophages (phages for short) are natural viruses that can selectively target and kill bacteria. They are considered to have a high therapeutic potential for the treatment of severe bacterial infections and especially BJI, as they also target biofilms. Here we report on the management of a patient with a pandrug-resistant Pseudomonas aeruginosa spinal abscess who was treated with surgery and a personalized combination of phage therapy that was added to antibiotics. As the infecting P. aeruginosa strain was resistant to the phages developed by private companies that were contacted, we set up a unique European academic collaboration to find, produce and administer a personalized phage cocktail to the patient in due time. After two surgeries, despite bacterial persistence with expression of small colony variants, the patient healed with local and intravenous injections of purified phages as adjuvant therapy.

| S-EPMC9306240 | biostudies-literature

Stability and low induction propensity of cefiderocol against chromosomal AmpC ?-lactamases of Pseudomonas aeruginosa and Enterobacter cloacae.

Project description:ObjectivesThe siderophore cephalosporin cefiderocol possesses in vitro activity against MDR Gram-negative bacteria. The stability of cefiderocol against serine- and metallo-type carbapenemases has been reported previously, but little is known about how cefiderocol interacts with chromosomal AmpC ?-lactamases. We investigated a number of features of cefiderocol, namely antibacterial activity against AmpC overproducers, stability against AmpC ?-lactamases and propensity for AmpC induction using Pseudomonas aeruginosa and Enterobacter cloacae.MethodsMICs were determined by broth microdilution according to CLSI guidelines. The MIC of cefiderocol was determined in iron-depleted CAMHB. Hydrolysis of the antibiotics was determined by monitoring the changes in the absorbance in the presence of AmpC ?-lactamase, and AmpC induction was evaluated by double disc diffusion and nitrocefin degradation assays.ResultsThe MICs of ceftazidime and cefepime for PAO1 increased 4- to 16-fold with inactivation of either ampD or dacB, whereas cefiderocol MICs were little affected by these inactivations (<2-fold increase). Cefiderocol has 17- and 740-fold lower affinity (higher Ki) to AmpCs of P. aeruginosa SR24-12 and E. cloacae P99, respectively, compared with ceftazidime. Both disc diffusion and nitrocefin degradation assays indicated that cefiderocol did not induce AmpC ?-lactamases of P. aeruginosa PAO1 and ATCC 27853 and E. cloacae ATCC 13047, whereas imipenem did.ConclusionsCefiderocol showed in vitro activity against the AmpC-overproducing strains, low affinity for chromosomal AmpC ?-lactamases, and a low propensity of temporal induction of AmpC ?-lactamases of P. aeruginosa and E. cloacae. These features relating to chromosomal AmpC could explain the potent antibacterial activity of cefiderocol against drug-resistant strains producing AmpC ?-lactamases.

| S-EPMC6198743 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data