Prescription Pattern of Intravenous Fosfomycin in a Provincial Hospital in Thailand

Thampithak Anusorn,Chaisiri Kessarin,Siangsuebchart Onrumpa,Phengjaturat Kamonchanok,Aonjumras Wiwarin,Hemapanpairoa Jatapat 대한감염학회 2022 Infection and Chemotherapy Vol.54 No.4

Background In Thailand, active antibiotics against Gram-negative bacteria are limited. The re-emergence of intravenous (IV) fosfomycin is an alternative. IV fosfomycin has broad-spectrum activity, relative safety, and availability. The limitations of the clinical use of IV fosfomycin include the lack of susceptibility reports and unclear dosing. Therefore, this study was designed to examine the prescription pattern of IV fosfomycin in Chonburi Hospital, a provincial hospital in Thailand. Materials and Methods A retrospective descriptive study involving in-patients aged ≥18 years who received IV fosfomycin between February 2019 and January 2020. Data were collected from the electronic patient records. Results Of 265 patients, 254 (95.8%) and 11 (4.2%) received IV fosfomycin for treatment and prophylaxis, respectively. IV fosfomycin was prescribed for empirical and definitive treatment. All 166 organisms were Gram-negative bacteria (GNB), including Enterobacterales (47.0%), Acinetobacter baumannii (44.0%), and Pseudomonas aeruginosa (9.0%). Moreover, 141 (87.6%) isolates were carbapenem-resistant GNB (CR-GNB). The most commonly used IV fosfomycin regimen contained colistin or aminoglycosides. Furthermore, 35.3% of the combination regimens contained one active antibiotic. The appropriate dosage of IV fosfomycin for treating urinary tract infection was 71.8%. The 14-day all-cause mortality rate in CR-GNB was 45.0%. Conclusion IV fosfomycin is reserved for secondary use in treating nosocomial infection with resistant GNB. It is used synergistically with other antibiotics. At least one active antibiotic and the optimal fosfomycin dosage should be considered. An antimicrobial stewardship program should be implemented for the optimal use of fosfomycin. Background In Thailand, active antibiotics against Gram-negative bacteria are limited. The re-emergence of intravenous (IV) fosfomycin is an alternative. IV fosfomycin has broad-spectrum activity, relative safety, and availability. The limitations of the clinical use of IV fosfomycin include the lack of susceptibility reports and unclear dosing. Therefore, this study was designed to examine the prescription pattern of IV fosfomycin in Chonburi Hospital, a provincial hospital in Thailand. Materials and Methods A retrospective descriptive study involving in-patients aged ≥18 years who received IV fosfomycin between February 2019 and January 2020. Data were collected from the electronic patient records. Results Of 265 patients, 254 (95.8%) and 11 (4.2%) received IV fosfomycin for treatment and prophylaxis, respectively. IV fosfomycin was prescribed for empirical and definitive treatment. All 166 organisms were Gram-negative bacteria (GNB), including Enterobacterales (47.0%), Acinetobacter baumannii (44.0%), and Pseudomonas aeruginosa (9.0%). Moreover, 141 (87.6%) isolates were carbapenem-resistant GNB (CR-GNB). The most commonly used IV fosfomycin regimen contained colistin or aminoglycosides. Furthermore, 35.3% of the combination regimens contained one active antibiotic. The appropriate dosage of IV fosfomycin for treating urinary tract infection was 71.8%. The 14-day all-cause mortality rate in CR-GNB was 45.0%. Conclusion IV fosfomycin is reserved for secondary use in treating nosocomial infection with resistant GNB. It is used synergistically with other antibiotics. At least one active antibiotic and the optimal fosfomycin dosage should be considered. An antimicrobial stewardship program should be implemented for the optimal use of fosfomycin.

Fosfomycin의 Vancomycin 내성 장구균에 대한 항균제 감수성

박순덕,어영,황규열,윤갑준,김효열 대한감염학회 2001 감염 Vol.33 No.3

Background : Vancomycin-resistant enterococci (VRE) were first recovered from clinical isolates in Korea in 1992, and the incidence has been steadily increasing. Alternatives to vancomycin are few because VRE are frequently resistant to commonly used antimicrobial agents. The present study was designed to assess the in-vitro activity of fosfomycin to clinical isolates of VRE. Methods : For 199 VRE isolates from 1995 to 2000, and 91 enterococcal isolates that were consecutively isolated during the January of 2001 at Wonju Christian Hospital, fosfomycin (200 μg) disk diffusion test was done by NCCLS method. The number of enterococcal isolates tested for fosfomycin were as follows : 58 E. faecalis (42 vancomycin susceptible isolates, 16 vancomycin resistant isolates, and 1 vancomycin in termediate resistance isolate); 210 E. faecium (185 vancomycin resistant and 25 vancomycin susceptible isolates); 15 E. gallinarum, and 6 E. casseliflavus isolates. Results : Among the VRE isolates, the resistance rates of fosfomycin according to enterococcal species were 6.3% in E. faecalis, 4.9% in E. faecium, 0% in E. casseliflavus, and 16.7% in E. gallinarum. Conclusion : Fosfomycin could be a potentially useful drug for the treatment of infections caused by VRE. (Korean J Infect Dis 33:181∼185, 2001)

The Antibiotic Susceptibility of Escherichia coli from Community-Acquired Uncomplicated Urinary Tract Infection: A Focused on Fosfomycin

최현섭,이승주,장인호,김태형,정홍,정재민,이상돈,정재흥,김기호,민승기,나용길,윤하나,유호송,이미경,이선주 대한요로생식기감염학회 2017 Urogenital Tract Infection Vol.12 No.2

Purpose: To assess the antibiotic susceptibility of Escherichia coli from commu-nity-acquired uncomplicated urinary tract infection (UTI).Materials and Methods: Between August and December of 2015, confirmed cases of E. coli as a pathogen of community-acquired uncomplicated UTI were collected and assessed for antibiotic susceptibility in 10 designated hospitals. Additional fosfomycin susceptibility test was performed by a central laboratory using the disk diffusion method.Results: A total of 347 E. coli isolates were collected from urine samples of community-acquired uncomplicated UTIs patients. The susceptibility rates of antibiotics were as follows: amikacin 100.0% (347), imipenem 100.0% (347), ciprofloxacin 57.1% (198), cefotaxime 74.9% (260), ampicillin 30.0% (104), trimethoprim/sulfamethoxazole 66.9% (232), and fosfomycin 98.0% (340). All fosfomycin-resistant E. coli isolates were extended-spectrum -lactamase (ESBL)-producing. In 85 cases of ESBL-producing E. coli, the fosfomycin susceptibility rate was 91.8% (78/85).Conclusions: Fosfomycin may be a useful option for the treatment of community-acquired uncomplicated UTIs. Further studies evaluating the role of fosfomycin in the treatment of UTIs and its clinical efficacy are necessary.

기니픽에서 Cisplatin 이독성에 대한 Fosfomycin, Pentoxifylline의 효과에 대한 주사현미경적 연구

김춘동,홍순관 梨花女子大學校 醫科大學 醫科學硏究所 1997 EMJ (Ewha medical journal) Vol.20 No.2

Objectives : The use of cis-platinum as therapeutic drug in malignant neoplasm has associated side effects such as nephrotoxicity and ototoxicity. The nephrotoxic effects of this drug is decreased by use of hydration method. The ototoxic effect, however, cause a irreversible sensorineural hearing loss and incidence of ototoxicity is not changed, so prevention of ototoxic effect is important. Methods : The efficacies of fosfomycin, agent in ameliorating cisplatin induced ototoxicity, are investigated in guinea pig cochleas and the effects of pentoxifylline, agent in therapeutic drug of idiopathic sensorineural hearing loss, are evaluated anatomically by cochlear histology with scanning eletromicroscopy. Results : Protection against the distortion and injury of outer hair cell according to position of the cochlea caused by cicplatin was statistically significant in groups injected with fosfomycin. Also the injury of hair cells seen in groups injected with both pentoxifyllin and cisplatin was significantly higher than that of cisplatin only group. Conclusion ; Fosfomycin protects against cisplatin induced ototoxicity but pentoxifylline does not protect cesplatin induced ototoxicity.

기니픽에서 Cisplatin 이독성에 대한 Fosfomycin의 예방적 효과

정원호,김종선 대한이비인후과학회 1998 대한이비인후과학회지 두경부외과학 Vol.41 No.2

Crystallization and Preliminary X-Ray Crystallographic Analysis of UDP-N-Acetylglucosamine Enolpyruvyl Transferase from Haemophilus influenzae in Complex with UDP-N-Acetylglucosamine and Fosfomycin

서세원,윤혜진,Min-Je Ku,Hyung Jun Ahn,이병일,Bunzo Mikami 한국분자세포생물학회 2005 Molecules and cells Vol.19 No.3

The bacterial enzyme UDP-N-acetylglucosamine enolpyruvyl transferase catalyzes the first committed step of peptidoglycan biosynthesis, i.e., transfer of enolpyruvate from phosphoenolpyruvate to UDP-N-acetylglucosamine. We have overexpressed the enzyme from Haemophilus influenzae in Escherichia coli and crystallized it in the apo-form, as well as in a complex with UDP-Nacetylglucosamine and fosfomycin using ammonium sulfate as the precipitant. X-ray diffraction data from a crystal of the apo-form were collected to 2.8 Å resolution at 293 K. The crystal quality was improved by co-crystallization with UDP-N-acetylglucosamine and fosfomycin. X-ray data to 2.2 Å have been collected at 100 K from a flash-frozen crystal of the complex. The complex crystals belong to the orthorhombic space group I222 (or I212121) with unit-cell parameters of a = 63.7, b = 124.5, and c = 126.3 Å. Assuming a monomer of the recombinant enzyme in the crystallographic asymmetric unit, the calculated Matthews parameter (VM) is 2.71 Å3 Da−1 and solvent content is 54.6%.

MS-2 system을 이용한 황색포도구균에 대한 moxalactam과 fosfomycin의 병용효과 측정

박찬석,안태휴,Park, Chan-Sok,Ahn, Tai-Hew 대한미생물학회 1986 大韓微生物學會誌 Vol.21 No.3

Twenty strains of penicillin(PC)-resistant Staphylococcus aureus ($MIC{\geqq}32U/ml$) were chosen randomly from recent isolates and submitted to the present experiment to see what effect the combined antibiotic action of moxalactam(MX) and fosfomycin(FM) would bring about on the cells, using MS-2 system. 1. The conventional agar dilution method and the rapid automatic MS-2 system were used in measuring the MICs of MX and FM against each strain and the comparison of the data obtained revealed no significant difference between the two methods in the titer and distribution of the MICs. 2. The automatic MS-2 system was, therefore, used alone in determining the combined growth inhibitory effect of MX and FM because of its more rapidness, and the obtained results were that most of the PC-resistant strains(16 out of 20, 80%) were synergistically inhibited by the two antibiotic combination while additive effect was observed in the remaining 4 strains(20%). 3. Thus, it is suggested that the growth of PC-resistant staphylococcal cells may be synergistically inhibited by MX and FM combination and the efficiency of two antibiotic action as well as MIC of single antibiotic may be more rapidly determined by the MS-2 system than by the conventional method.

Effectiveness of fosfomycin-based antimicrobial prophylaxis for transrectal ultrasound-guided prostate biopsy: A Korean multicenter study

임도경,정승일,황의창,김태형,배상락,허정식,이승주,정홍,최훈 대한비뇨의학회 2023 Investigative and Clinical Urology Vol.64 No.3

Purpose: Recent studies have highlighted increasing infectious complications due to fluoroquinolone (FQ)-resistant organisms in men undergoing transrectal ultrasound-guided prostate biopsy (TRUSPB). This study investigated whether fosfomycin (FM)-based antibiotic prophylaxis reduces infections after TRUSPB and identified risk factors for infective complications. Materials and Methods: A multicenter study was conducted in the Republic of Korea from January 2018 to December 2021. Patients undergoing prostate biopsy with FQ or FM-based prophylaxis were included. The primary outcome was the post-biopsy infectious complication rate after FQ (group 1) or FM-based antibiotic prophylaxis with FM alone (group 2) or FQ and FM (group 3). Risk factors for infectious complications after TRUSPB were secondary outcomes. Results: Patients (n=2,595) undergoing prostate biopsy were divided into three groups according to the type of prophylactic antibiotics. Group 1 (n=417) received FQ before TRUSPB. Group 2 (n=795) received FM only and group 3 (n=1,383) received FM and FQ before TRUSPB. The overall post-biopsy infectious complication rate was 1.27%. The infectious complication rates were 2.4%, 1.9%, and 0.5% in groups 1, 2, and 3, respectively (p=0.002). In multivariable analysis, predictors of post-biopsy infectious complications included an association with health care utilization (adjusted odds ratio [OR], 4.66; 95% confidence interval [CI], 1.74–12.4; p=0.002) and combination antibiotic prophylaxis (FQ and FM) (adjusted OR, 0.26; 95% CI, 0.09–0.69; p=0.007). Conclusions: In comparison with monotherapy with FM or FQ, combination antibiotic prophylaxis (FQ and FM) showed a lower rate of infectious complications after TRUSPB. Utilization of health care was an independent risk factor for infectious complications after TRUSPB.

Fosfomycin Dosing Regimens based on Monte Carlo Simulation for Treated Carbapenem-Resistant Enterobacteriaceae Infection

Kanchanasurakit Sukrit,Santimaleeworagun Wichai,Charles E. McPherson, III,Piriyachananusorn Napacha,Boonsong Benjawan,Katwilat Papanin,Saokaew Surasak 대한감염학회 2020 Infection and Chemotherapy Vol.52 No.4

Background: Infections by Carbapenem-Resistant Enterobacteriaceae (CRE) remain a leading cause of death in critically ill patients. Fosfomycin has been regarded as an alternative therapy for treatment of infections caused by CRE organisms. The purpose of this study is to evaluate clinical outcomes amongst patients with CRE infection who are receiving a fosfomycin dosing regimen using a Monte Carlo simulation and fosfomycin minimum inhibitory concentration (MIC). Materials and Methods: Fosfomycin MIC was defined by the E-test method. We used Fosfomycin pharmacokinetic parameters from a previously published study. The percent of the time period in which the drug concentration exceeded the MIC, or %T>MIC, used in this study were determined to be 70% of T>MIC and 100% of T>MIC, respectively. All dosing regimens were estimated for the probability of target attainment using a Monte Carlo simulation. Results: In this study, we found the MIC's of fosfomycin against CRE isolates ranged from 8 mg/L to 96 mg/L. The total daily dose of fosfomycin ranged from 16 - 24 g and was administered utilizing various fosfomycin dosing regimens to achieve the pharmacokinetic/ pharmacodynamic (PK/PD) target in pathogens with a MIC of 32 mg/L for 70%T>MIC and a MIC of 12 mg/L for 100%T>MIC, respectively. For the twelve patients who received the recommended fosfomycin dosing regimen, eleven achieved bacterial eradication for a microbiological cure rate of 91%; and of those patients achieving eradication, two died despite having negative cultures for CRE; the one remaining patient had bacterial persistence. The most commonly observed adverse drug reactions were hypernatremia (3 cases) and hypokalemia (3 cases) and acute kidney injury (3 cases). Conclusion: Our findings suggest fosfomycin has tended to good efficacy when using dosing regimens that achieve the PK/PD target. Nonetheless, further validation of these regimens in larger populations is needed.

Susceptibility to Fosfomycin and Nitrofurantoin of ESBL-Positive Escherichia coli and Klebsiella pneumoniae Isolated From Urine of Pediatric Patients

Park Ki-Sup,Kim Doo Ri,Baek Jin Yang,Shin Areum,Kim Kyung-Ran,Park Hwanhee,Son Sohee,Cho Heeyeon,Kim Yae-Jean 대한의학회 2023 Journal of Korean medical science Vol.38 No.48

Background: Pediatric urinary tract infection (UTI) caused by extended-spectrum β-lactamase (ESBL)-positive gram-negative bacilli (GNB) has limited options for oral antibiotic treatment. The purpose of this study was to investigate the susceptibility of ESBLpositive Escherichia coli and Klebsiella pneumoniae isolates from pediatric urine samples to two oral antibiotics (fosfomycin and nitrofurantoin). Methods: From November 2020 to April 2022, ESBL-positive E. coli and K. pneumoniae isolates from urine samples were collected at Samsung Medical Center, Seoul, Korea. Patients over 18 years of age or with malignancy were excluded. For repeated isolates from the same patient, only the first isolate was tested. Minimum inhibitory concentrations (MICs) were measured using agar (fosfomycin) or broth (nitrofurantoin) dilution methods. MIC50 and MIC90 were measured for fosfomycin and nitrofurantoin in both E. coli and K. pneumoniae. Results: There were 117 isolates from 117 patients, with a median age of 7 months (range, 0.0–18.5 years). Among 117 isolates, 92.3% (108/117) were E. coli and 7.7% (9/117) were K. pneumoniae. Isolates from the pediatric intensive care unit (PICU) and general ward (GW) was 11.1% (13/117) and 88.9% (104/117), respectively. Among 108 E. coli isolates, MIC50 and MIC90 for fosfomycin were 0.5 μg/mL and 2 μg/mL, respectively. Fosfomycin susceptibility rate was 97.2% (105/108) with a breakpoint of 128 μg/mL. Fosfomycin susceptibility rate was significantly lower in PICU isolates than in GW isolates (81.8% vs. 99.0%, P = 0.027). For nitrofurantoin, both the MIC50 and MIC90 were 16 μg/mL. Nitrofurantoin susceptibility rate was 96.3% (104/108) with a breakpoint of 64 μg/mL based on Clinical and Laboratory Standards Institute guidelines. Among the nine K. pneumoniae isolates, the MIC50 and MIC90 for fosfomycin was 2 μg/mL and 32 μg/mL, respectively. MIC50 and MIC90 for nitrofurantoin were 64 μg/mL and 128 μg/mL, respectively. Conclusion: For uncomplicated UTI caused by ESBL-positive GNB in Korean children, treatment with fosfomycin and nitrofurantoin for E. coli infections can be considered as an effective oral therapy option.