Efficacy and safety of intravenous fosfomycin for the treatment of difficult-to-treat Gram-negative bacterial infections

Abdallah, Tasneem; Elajez, Reem; Ibrahim, Tawheeda; Alimam, Abeir; Omrani, Ali S.

doi:10.1016/j.jiph.2021.09.025

Cited by 12 publications

(4 citation statements)

References 5 publications

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“…Furthermore, it is hard to tell if the other adverse reactions reported (fatigue, anorexia, dyspnea and tachycardia) were caused by the antibiotic itself, rather than by the concomitant medications and clinical conditions. These data are consistent with the current literature, which shows a favorable safety profile of fosfomycin, with adverse reactions generally mild and not requiring discontinuation of treatment, [22][23][24][25] although studies in exclusively pediatric populations are still scarce. 26 Our study has many limitations.…”

Section: Discussionsupporting

confidence: 91%

Back to the Future: Intravenous Fosfomycin is Safe and Effective for the Treatment of Complicated Infections in Children

Roversi,

Musolino,

Di Giuseppe

et al. 2024

Pediatric Infectious Disease Journal

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Background: Despite its broad spectrum and excellent safety profile, fosfomycin is still rarely used in pediatrics, with very limited experience from clinicians. Methods: We retrospectively reviewed the medical records of all children admitted to Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy, and treated with fosfomycin for any serious infection. Children with immunodeficiency and oncological diseases were excluded. Of each, we reported and analyzed demographic and clinical data. Results: The clinical charts of 20 patients were reviewed and analyzed. The mean age was 10.2 years. Most children were males (85%). Most patients treated had an osteo-articular infection (65%). In our sample, 7 patients (35%) had an underlying comorbidity. The causative agent was isolated in 14 cases (70%). All patients were treated with a combination of 2–3 antibiotics, including fosfomycin. The average duration of antibiotic treatment was 18 days. After treatment, 8 patients (40%) experienced a mild adverse reaction, possibly correlated with the administration of fosfomycin. All patients were discharged in good clinical condition. Conclusions: The present study reports on a sample of pediatric patients with complicated infections where administration of fosfomycin led to eradication of the disease with little or no side effects. Role of the underlying condition and concomitant medication in causing the reaction could not be ruled out. These data suggest that fosfomycin is an effective and safe antibiotic in the pediatric population, particularly for deep-seated infections sustained by multi-drug resistant pathogens.

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Section: Discussionsupporting

confidence: 91%

Back to the Future: Intravenous Fosfomycin is Safe and Effective for the Treatment of Complicated Infections in Children

Roversi,

Musolino,

Di Giuseppe

et al. 2024

Pediatric Infectious Disease Journal

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“… 14 Importantly, a previous study revealed that 226 (78%) of the isolates out of the 288 meropenem-resistant Kp strains were DTRs. 15 A previous retrospective study showed that the most frequent target organism was Kp (17, 56.7%) in hospitalized DTR GNB-infected patients who received IV fosfomycin for ≥48 h. 16 Of note, DTR-Kp is rapidly emerging, indicating that close attention should be given to it.…”

Section: Introductionmentioning

confidence: 99%

Clinical Outcomes, Microbiological Characteristics and Risk Factors for Difficult-to-Treat Resistance to Klebsiella pneumoniae Infection

Yang¹,

Liu²,

Wu³

et al. 2022

IDR

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Purpose This study aimed to identify the clinical outcomes, microbiological features and risk factors for difficult-to-treat resistance (DTR) Klebsiella pneumoniae (Kp) infection. Materials and Methods A retrospective study was conducted at Peking University Third Hospital from January 2020 to March 2021. DTR was defined as resistance to ≥1 carbapenem, ≥1 extended-spectrum cephalosporin, and ≥1 fluoroquinolone. Hypervirulent Kp (HvKp) was defined as peg-344-, iroB-, iucA-, rmpA- , or rmpA2 -positive. Clinical data were collected. Antimicrobial susceptibility testing and string tests were performed to determine resistance and hypermucoviscosity phenotype. Whole genome sequencing was performed to analyze the sequence type (ST), capsular serotypes, resistance and virulence genes. Risk factors for 30-day mortality were analyzed. Results Fifty DTR-Kp (50.0%) strains were identified among 100 patients. Compared to non-DTR-Kp group, a significant number of patients with DTR-Kp infection experienced ICU admission (44.0% versus 10.0%, P<0.001) and mechanical ventilation after Kp detection (26.0% versus 10.0%, P=0.037). Notably, the percentage of hvKp among the DTR-Kp isolates increased consistently over the 15 months evaluated. Most DTR-Kp strains belonged to ST11 (82.0%), followed by ST15 (12.0%), ST86 (2.0%), ST996 (2.0%), and ST3157 (2.0%). DTR-Kp isolates possessed various resistance genes, such as bla KPC-2 , bla TEM-1D and fosA3 (90.0%, 80.0% and 72.0%, respectively). Importantly, the yersiniabactin genes were significantly clustered in DTR group (48/50, 96.0%). The 30-day mortality was significantly higher in patients with DTR-Kp infection than non-DTR-Kp group (38.0% versus 8.2%, P=0.001). DTR-Kp infection (odds ratio [OR] = 4.196) was an independent risk factor for the 30-day mortality of Kp-infected patients. Additionally, cerebrovascular disease (OR = 2.780) and Charlson comorbidity index (OR= 1.584) were independent risk factors for DTR-Kp infections. Conclusion DTR-hvKp is rapidly emerging. The DTR-Kp strains harbored various resistance genes and high rates of yersiniabactin siderophore genes. DTR-Kp infection was an independent risk factor for mortality, suggesting that enhanced awareness essential.

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“…IV fosfomycin was found to be well tolerated and safe in almost all cases analyzed, with no occurrence of serious adverse effects. Only a small percentage of electrolyte disturbances (hypokalemia and/or hypernatremia) and gastrointestinal disturbances were found to be 2.6% and 2.9%, respectively, as already highlighted in other studies [10,24,33] and much less than that found in the cohort of Zirpe et al [34]. However, this study does not remain free of limitations, ascertainable to its retrospective nature and the vast heterogeneity of the clinical setting of the patients for whom fosfomycin was used.…”

Section: Discussionmentioning

confidence: 55%

“…Regarding S.aureus and E.coli isolates, all those analyzed were sensitive to fosfomycin, confirming the finding already evaluated by Maraki et al [ 22 ]. In our cohort, fosfomycin was used almost exclusively in combination with other antibiotics (94.4% of patients), supported by synergistic effects as recently recommended, especially if MDR Gram-negative pathogens are involved [ 13 , 23 , 24 ]. Remarkably, EUCAST stated that there are not enough data for providing any meaningful clinical breakpoint of fosfomycin against P.aeruginosa or A.baumannii , but our use in these types of infections was based on several clinical data on the efficacy of IV fosfomycin in combination with other antibiotics mainly derived from observational studies [ 25 , 26 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

The Use of Intravenous Fosfomycin in Clinical Practice: A 5-Year Retrospective Study in a Tertiary Hospital in Italy

et al. 2023

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Fosfomycin in intravenous (IV) formulation has re-emerged as a valuable tool in the treatment of multi-drug resistant (MDR) and extensively drug-resistant (XDR) infections because of its broad spectrum of antibacterial action and pharmacokinetic characteristics. This retrospective study aimed to evaluate how fosfomycin was used in patients admitted to the Polyclinic of Palermo between January 2017 and July 2022. Clinical indications, therapeutic associations, clinical outcomes, and any side effects were analyzed. Intravenous fosfomycin was used in 343 patients, 63% male, with a mean age of 68 years (range 15–95). Urinary tract infections (UTIs) and hospital-acquired pneumonia (HAP) were the main indications for treatment (19% and 18% of the total cases, respectively), followed by skin and soft tissue infections and sepsis. IV fosfomycin was administered in combination with other antibacterial agents, the most common of which were ceftazidime/avibactam (35%), meropenem (17%), and colistin (14%). Nineteen patients received it as monotherapy for UTIs. About 66% had resolution of the infectious process with clinical remission (cure or discharge). Electrolyte disturbances occurred in 2.6% and gastrointestinal symptoms occurred in 2.9%. The data showed that IV fosfomycin is a safe and effective therapeutic option in the treatment of infections with multidrug-resistant microorganisms.

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Efficacy and safety of intravenous fosfomycin for the treatment of difficult-to-treat Gram-negative bacterial infections

Cited by 12 publications

References 5 publications

Back to the Future: Intravenous Fosfomycin is Safe and Effective for the Treatment of Complicated Infections in Children

Back to the Future: Intravenous Fosfomycin is Safe and Effective for the Treatment of Complicated Infections in Children

Clinical Outcomes, Microbiological Characteristics and Risk Factors for Difficult-to-Treat Resistance to Klebsiella pneumoniae Infection

The Use of Intravenous Fosfomycin in Clinical Practice: A 5-Year Retrospective Study in a Tertiary Hospital in Italy

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