fosfomycin and Sepsis

To systematically review and meta-analyse available evidence comparing fosfomycin trometamol (FT) to fluoroquinolone (FQ) prophylaxis to prevent transrectal ultrasound-guided prostate biopsy (TRUSPB) related infectious complications.. Electronic databases were queried for studies comparing FT to FQ-based TRUSPB prophylaxis. Studies were assessed for comparable outcomes and methodological quality (ROBINS-I modification). The primary outcome measure was the relative odds of overall infectious complications following TRUSPB according to FT/FQ treatment, which was evaluated with meta-analysis. Safety and tolerability were also assessed. The relative odds of infections of different severity [Grade 1, bacteriuria and afebrile urinary tract infection (UTI); Grade 2, bacteraemia, febrile UTI, and urosepsis] according to FT/FQ treatment were also estimated.. Five studies, being three prospective randomised trials and two retrospective cohort studies, representing 3112 patients, were included. The relative odds of an infectious complication (OR 0.22, 95% CI 0.09-0.54) or of a more severe (Grade 2) infection (OR 0.13, 95% CI 0.07-0.26) were significantly lower in those receiving FT compared to FQ prophylaxis. A low incidence of medication-related side effects was observed. There were less observed infections due to FQ-resistant pathogens in those receiving FT prophylaxis.. Patients who received FT prophylaxis were less likely than those who received FQ prophylaxis to develop infections overall, as well as severe and resistant infections after TRUSPB. Assessing the performance of FT in other geographic locations or in comparison to targeted prophylaxis based on risk assessment or rectal cultures is desired.

Topics: Aged; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacteremia; Biopsy, Large-Core Needle; Ciprofloxacin; Fluoroquinolones; Fosfomycin; Humans; Image-Guided Biopsy; Levofloxacin; Male; Middle Aged; Prostate; Sepsis; Ultrasonography; Urinary Tract Infections

The objective of this study was to describe the microbiological characteristics of an extensively drug-resistant (XDR) isolate of Morganella morganii obtained from a patient with sepsis of urinary origin and to describe the patient's clinical characteristics. We further aimed to perform a literature review of the situation in Latin America regarding Gram-negative bacillus (GNB) carriers of New Delhi metallo-β-lactamase (NDM-1) and qnr genes and current reports on the treatment of infections caused by XDR enterobacteria, with particular attention to colistin-resistant isolates.. The patient's clinical data were obtained from his medical history. Microbiological identification and susceptibility testing were done using the VITEK 2 Compact System. Resistance genes were detected by PCR and sequencing.. Blood and urine cultures grew an M. morganii isolate (Mm4232) harboring NDM-1 and qnrD1. The patient was treated successfully with fosfomycin and double doses of meropenem. There are no previous reports of the use of fosfomycin and meropenem to treat infections by XDR enterobacteria harboring NDM-1 carbapenemase.. This is the first report of qnrD1 in South America. We consider that this report could be helpful to physicians implementing treatments for infections caused by XDR GNB, including colistin-carbapenem-resistant GNB.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Drug Therapy, Combination; Enterobacteriaceae Infections; Fosfomycin; Humans; Male; Meropenem; Morganella morganii; Sepsis; South America; Thienamycins; Young Adult

Topics: Anti-Infective Agents, Urinary; Bacteriuria; Cephalosporins; Chronic Disease; Cystitis; Drug Resistance, Bacterial; Fluoroquinolones; Fosfomycin; Humans; Microbial Sensitivity Tests; Nitrofurantoin; Pyelonephritis; Recurrence; Risk Factors; Sepsis; Tromethamine; Urinary Tract Infections

To assess pharmacokinetics and changes to sodium levels in addition to adverse events (AEs) associated with fosfomycin among neonates with clinical sepsis.. A single-centre open-label randomised controlled trial.. Kilifi County Hospital, Kenya.. 120 neonates aged ≤28 days admitted being treated with standard-of-care (SOC) antibiotics for sepsis: ampicillin and gentamicin between March 2018 and February 2019.. We randomly assigned half the participants to receive additional intravenous then oral fosfomycin at 100 mg/kg two times per day for up to 7 days (SOC-F) and followed up for 28 days.. Serum sodium, AEs and fosfomycin pharmacokinetics.. 61 and 59 infants aged 0-23 days were assigned to SOC-F and SOC, respectively. There was no evidence of impact of fosfomycin on serum sodium or gastrointestinal side effects. We observed 35 AEs among 25 SOC-F participants and 50 AEs among 34 SOC participants during 1560 and 1565 infant-days observation, respectively (2.2 vs 3.2 events/100 infant-days; incidence rate difference -0.95 events/100 infant-days (95% CI -2.1 to 0.20)). Four SOC-F and 3 SOC participants died. From 238 pharmacokinetic samples, modelling suggests an intravenous dose of 150 mg/kg two times per day is required for pharmacodynamic target attainment in most children, reduced to 100 mg/kg two times per day in neonates aged <7 days or weighing <1500 g.. Fosfomycin offers potential as an affordable regimen with a simple dosing schedule for neonatal sepsis. Further research on its safety is needed in larger cohorts of hospitalised neonates, including very preterm neonates or those critically ill. Resistance suppression would only be achieved for the most sensitive of organisms so fosfomycin is recommended to be used in combination with another antimicrobial.. NCT03453177.

Topics: Anti-Bacterial Agents; Child; Fosfomycin; Gentamicins; Humans; Infant; Infant, Newborn; Neonatal Sepsis; Sepsis; Sodium

This study sought to evaluate the antibacterial effect of fosfomycin tromethamine (FT) on the bacteria inside urinary infection stones.. The internal structures of urinary stones were observed via scanning electron microscopy to verify the presence of internal bacteria. We randomly assigned equal numbers of patients with kidney stones who met the inclusion criteria into two groups in a prospective study and treated them with different perioperative antibiotics. One group (experimental group) was treated with FT, and the other (control group) was treated with cefuroxime sodium. All stone specimens were collected via percutaneous nephrolithotomy (PCNL). The primary infection stones were screened via a stone component analysis, 30 cases in the experimental group and 31 cases in the control group. High-performance liquid chromatography (HPLC)-mass spectrometry was used to measure the drug concentration inside the stones, the bacterial count was calculated via stone culture, and the clinical infection index were monitored for between-group comparisons.. Compared with the control group, the experimental group had a higher internal drug concentration, a higher drug sensitivity against various pathogenic bacteria, a lower bacterial colony count in the stone culture, and a lower incidence of postoperative clinical infection.. FT is more effective than cefuroxime, which is commonly used during the perioperative period of urinary stones, and exerts a high antibacterial effect on these internal bacteria, and effectively reduces the probability of infection and sepsis after urinary stone surgery. FT can be used as an antibiotic during the perioperative period of urinary stones.

Topics: Adult; Aged; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacteria; Cefuroxime; Colony Count, Microbial; Female; Fever; Fosfomycin; Humans; Kidney Calculi; Male; Middle Aged; Nephrolithotomy, Percutaneous; Postoperative Complications; Prospective Studies; Sepsis

In Europe, intravenous fosfomycin (IV) is used particularly in difficult-to-treat or complex infections, caused by both Gram-positive and Gram-negative pathogens including multidrug-resistant strains. Here, we investigated the efficacy and safety of intravenous fosfomycin under real-life conditions.. Prospective, multi-center, and non-interventional study in patients with bacterial infections from 20 intensive care units (ICU) in Germany and Austria (NCT01173575).. Overall, 209 patients were included (77 females, 132 males, mean age: 59 ± 16 years), 194 of which were treated in intensive care (APACHE II score at the beginning of fosfomycin therapy: 23 ± 8). Main indications (± bacteremia or sepsis) were infections of the CNS (21.5%), community- (CAP) and hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP, 15.3%), bone and joint infections (BJI, 11%), abdominal infections (11%), and bacteremia (10.5%). Most frequently identified pathogens were S. aureus (22.3%), S. epidermidis (14.2%), Enterococcus spp. (10.8%), E. coli (12.3%) and Klebsiella spp. (7.7%). At least one multidrug-resistant (MDR) pathogen was isolated from 51 patients (24.4%). Fosfomycin was administered with an average daily dose of 13.7 ± 3.5 g over 12.4 ± 8.6 days, almost exclusively (99%) in combination with other antibiotics. The overall clinical success was favorable in 81.3% (148/182) of cases, and in 84.8% (39/46) of patients with ≥ 1 MDR pathogen. Noteworthy, 16.3% (34/209) of patients developed at least one, in the majority of cases non-serious, adverse drug reaction during fosfomycin therapy.. Our data suggest that IV fosfomycin is an effective and safe combination partner for the treatment of a broad spectrum of severe bacterial infections in critically ill patients.

Topics: Administration, Intravenous; Adult; Aged; Anti-Bacterial Agents; Austria; Bacteremia; Bacterial Infections; Critical Illness; Female; Fosfomycin; Germany; Humans; Intensive Care Units; Male; Middle Aged; Prospective Studies; Sepsis; Treatment Outcome

Consecutive adult patients requiring emergency abdominal surgery were randomly allocated to preoperative treatment with metronidazole-gentamicin (M-G) or metronidazole-fosfomycin (M-F). Postoperative continuation of antibiotics depended on the estimated risk of septic complications. Peroperatively the cases were stratified as group A, acute inflamed appendicitis, or absence of septic disorder--no postoperative antibiotics, group B, gangrenous appendicitis or cholecystitis or intestinal obstruction without resection, or operations with contamination regarded as minor (gastrotomy or enterotomy)--three further doses of antibiotics, or group C, perforated appendicitis, perforation of the alimentary tract, generalized peritonitis or gross contamination--antibiotics continued for 5 days. Assessment for septic complications was made in 381 patients (191 M-G, 190 M-F). The total incidence was 4.8% (M-G 7.8%, M-F 1.6%, p less than 0.01). The difference was mainly due to higher infection rate in patients stratified to group C and randomized to M-G. Stratification thus permitted restricted duration of antibiotic treatment with a low septic complication rate, significantly less with M-F than with M-G regimen.

Topics: Abdomen, Acute; Adolescent; Adult; Aged; Appendicitis; Cholecystitis; Clinical Trials as Topic; Drug Therapy, Combination; Female; Fosfomycin; Gentamicins; Humans; Male; Metronidazole; Middle Aged; Peritonitis; Postoperative Complications; Random Allocation; Sepsis

The aim of this randomized double-blind study comparing the efficacy of two prophylactic regimens, metronidazole/placebo (n = 23) and metronidazole/fosfomycin (n = 26) was two-fold. First, to evaluate the need for anti-aerobic cover in addition to short-term systemic administration of metronidazole against anaerobes in colorectal surgery. Secondly, to explore the prophylactic effect of fosfomycin on aerobes of intestinal origin. An unacceptably high rate of surgical sepsis (16.3%) forced premature conclusion of the study after 49 patients had entered it. All surgical and remote infections occurred in the metronidazole/placebo group and were caused solely by aerobes. Anaerobic sepsis was not seen at all and the surgical infection rate was 34.8%. No septic complications occurred in the 26 patients (0%) receiving metronidazole/fosfomycin (p less than 0.01). Thus the study demonstrated both the need to administer an effective anti-aerobic agent in addition to metronidazole in colorectal surgery and the efficacy of fosfomycin in preventing aerobic sepsis of intestinal origin. Adverse reactions to the two drugs were not observed and resistance did not occur.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteria, Aerobic; Bacteriological Techniques; Clinical Trials as Topic; Colonic Diseases; Double-Blind Method; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Fosfomycin; Humans; Male; Metronidazole; Middle Aged; Placebos; Premedication; Random Allocation; Rectal Diseases; Sepsis; Surgical Wound Infection

A comparative randomized study was designed to evaluate the prophylactic effect of two different combinations of antimicrobials, i.e. metronidazole-fosfomycin (n = 30) and metronidazole-cephalothin (n = 28), in elective colorectal surgery. The study was strictly consecutive and the treatment groups comparable. The total rate of surgical septic complications was low (10%) in both treatment groups. No anaerobic infections could be demonstrated and the clinical course was mild in all patients developing septic complications. No other antimicrobial therapy was given. Peroperative bacteriological sampling yielded aerobes and anaerobes in 51 and 32, respectively, of 58 patients. A high percentage of the isolated aerobes and anaerobes were cephalothin-resistant, whereas most aerobes were sensitive to fosfomycin. Only aerobes were isolated from surgical septic sites. The absence of anaerobic sepsis must be ascribed to the metronidazole prophylaxis; the probable reason for the low rate of surgical aerobic septic complications is that antimicrobials, active against aerobes, were included in the prophylactic regimens. The combination, metronidazole-fosfomycin, seems adequate and safe for continued evaluation.

Topics: Anti-Bacterial Agents; Bacterial Infections; Bacteroides; Cephalothin; Clinical Trials as Topic; Colon; Colonic Diseases; Drug Therapy, Combination; Escherichia coli; Fosfomycin; Humans; Metronidazole; Microbial Sensitivity Tests; Postoperative Complications; Random Allocation; Rectal Diseases; Rectum; Sepsis

This study examines the role of mesenchymal stem cells (MSCs) in an experimental sepsis model developed with colistin-resistant Acinetobacter baumannii (CRAB).. BALB-c mice were divided into treatment groups (MSC, MSC + colistin (C)-fosfomycin (F), and C-F and control groups (positive and negative)). CRAB was administered to mice through intraperitoneal injection. Three hours later, C, F, and MSC were given intraperitoneally to the treatment groups. Colistin administration was repeated every 12 h, F administration was done every 4 h, and the second dose of MSC was administered after 48 h. Mice were sacrificed at 24 and 72 h. The bacterial load was determined as colony-forming units per gram (cfu/g). Histopathological examination was conducted on the left lung, liver, and both kidneys. IL-6 and C-reactive protein (CRP) levels in mouse sera were determined by enzyme-linked immunosorbent assay.. Among the treatment groups, the C-F group had the lowest colony count in the lung (1.24 ± 1.66 cfu/g) and liver (1.03 ± 1.08 cfu/g). The highest bacterial clearance was observed at 72 h compared to 24 h in the MSC-treated groups (p = 0.008). The MSC + C-F group showed the lowest histopathological score in the liver and kidney (p = 0.009). In the negative control group, the IL-6 level at the 24th hour was the lowest (p < 0.001). Among the treatment groups, the CRP level was the lowest in the MSC + C-F group at 24 and 72 h.. In a CRAB sepsis model, adding MSCs to a colistin-fosfomycin treatment may be beneficial in terms of reducing bacterial loads and preventing histopathological damage.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Carbapenems; Colistin; Fosfomycin; Interleukin-6; Mesenchymal Stem Cells; Mice; Microbial Sensitivity Tests; Sepsis

The aim of this study was to evaluate the combination treatments with intravenous fosfomycin for carbapenem-resistant Klebsiella pneumoniae infections in a tertiary-care center.. Between December 24, 2018 and November 21, 2022, adult patients diagnosed with bloodstream infection or ventilator-associated pneumonia due to culture-confirmed carbapenem-resistant Klebsiella pneumoniae in the anesthesiology and reanimation intensive care units were investigated retrospectively.. There were a total of 62 patients fulfilling the study inclusion criteria. No significant difference was recorded in 14- and 30-day mortality among different types of combination regimens such as fosfomycin plus one or two antibiotic combinations. Hypokalemia (OR:5.651, 95%CI 1.019-31.330, p=0.048) was found to be a significant risk factor for 14-day mortality, whereas SOFA score at the time of diagnosis (OR:1.497, 95%CI 1.103-2.032, p=0.010) and CVVHF treatment (OR:6.409, 95%CI 1.395-29.433, p=0.017) were associated with 30-day mortality in multivariate analysis.. In our study, high mortality rates were found in patients with bloodstream infection or ventilator-associated pneumonia due to carbapenem-resistant Klebsiella pneumoniae, and no significant difference was recorded in 14- and 30-day mortality among different types of combination regimens such as fosfomycin plus one or two antibiotic combinations.

Topics: Adult; Anti-Bacterial Agents; Carbapenems; Fosfomycin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Pneumonia, Ventilator-Associated; Retrospective Studies; Sepsis

Topics: Animals; Anti-Bacterial Agents; Colistin; Fosfomycin; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Rats; Sepsis; Tobramycin

Vancomycin-resistant Enterococcus faecium (VREfm) infections are increasing. Current anti-VREfm options (linezolid and daptomycin) are suboptimal. Fosfomycin maintains good efficacy against VREfm and chloramphenicol is active against ≥ 90% of VREfm. We tested chloramphenicol + fosfomycin (CAF+FOS) against 10 VREfm isolated from blood. MICs were 64 to 512 µg/mL for fosfomycin and 8 to 16 µg/mL for chloramphenicol. The combination decreased both MICs, with a synergic effect in 50% of the isolates and an additive effect in the remaining 50%. Time-kill assays performed on fractional inhibitory concentration index ≤ 0.5 strains confirmed the synergism. The antibiotic combination at ¼ of minimum inhibitory concentrations (MICs) caused a ≥ 2 log

Topics: Animals; Anti-Bacterial Agents; Chloramphenicol; Disease Models, Animal; Drug Synergism; Enterococcus faecium; Fosfomycin; Gram-Positive Bacterial Infections; Humans; Kaplan-Meier Estimate; Microbial Sensitivity Tests; Moths; Sepsis; Vancomycin-Resistant Enterococci

Early and prompt treatment of sepsis by effective antibiotics against susceptible organisms may be lifesaving. However, increased antibiotic resistance and side effects of chemotherapeutic agents limiting their tolerability result in a restricted use of medications. This has led to an increased search for solution oriented novel treatments and therapeutic targets, as well as investigations on the pathogenesis and physiology of sepsis. In this study, we aimed to examine the antioxidant and anti-inflammatory effects of fosfomycin in sepsis resulting from other causes.. Sprague Dawley rats were assigned into three groups. Randomly selected control rats received intraperitoneal saline solution only. Only caecal puncture and ligation were carried out in the caecal ligation and puncture (CLP) group, while in the CLP + fosfomycin group (CLP + FOS), together with sepsis due to caecal puncture and ligation, 500 mg/kg of FOS was administered intraperitoneally (i.p.).. As compared to the control group, elevated TBARS and TNF-α levels as well as increased expression of NF-kB/p65 and TLR-4 and reduced -SH levels were found in the lung tissue of CLP rats. On the other hand, TBARS and TNF-α levels were reduced and NF-kB/p65 and TLR-4 expressions were decreased together with increase in total -SH levels among CLP + FOS (500 mg/kg i.p.) rats.. FOS treatment may represent a promising agent in terms of reducing the sepsis-related lung injury due to its antimicrobial effects as well as its antioxidant and anti-inflammatory properties.

Topics: Acute Lung Injury; Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antioxidants; Fosfomycin; Inflammation; Male; Oxidative Stress; Protective Agents; Rats; Rats, Sprague-Dawley; Sepsis

To assess fosfomycin (FOS) elimination in patients with sepsis and acute kidney injury (AKI) undergoing slow-extended daily dialysis (SLEDD) with the Genius system in a prospective observational study. After ethics committee approval ten patients with sepsis and AKI stage 3 underwent daily SLEDD sessions of eight hours. FOS was applied i.v. at doses of 3 × 5 g per day. FOS serum levels were measured pre- and post hemofilter before, during, and after SLEDD sessions, and instantaneous clearance was calculated. In five of the patients, we analyzed FOS levels after the first dose, in the other five patients serum levels were measured during ongoing therapy. FOS was eliminated rapidly via the hemofilter. FOS clearance decreased from 152 ± 10 mL/min (start of SLEED session) to 43 ± 38 mL/min (end of SLEDD session). In 3/5 first-dose patients after 4-6 h of SLEDD the FOS serum level fell below the EUCAST breakpoint of 32 mg/L for Enterobacterales and Staphylococcus species. In all patients with ongoing fosfomycin therapy serum levels were high and above the breakpoint at all times. FOS toxicity or adverse effects were not observed. FOS serum concentrations exhibit wide variability in critically ill patients with sepsis and AKI. FOS is eliminated rapidly during SLEDD. A loading dose of 5 g is not sufficient to achieve serum levels above the EUCAST breakpoint for common bacteria in all patients, considering that T > MIC > 70% of the dosing interval indicates sufficient plasma levels. We thus recommend a loading dose of 8 g followed by a maintenance dose of 5 g after a SLEDD session in anuric patients. We strongly recommend therapeutic drug monitoring of FOS levels in critically ill patients with AKI and dialysis therapy.

Topics: Acute Kidney Injury; Aged; Critical Illness; Dose-Response Relationship, Drug; Drug Monitoring; Enterobacter; Female; Fosfomycin; Hemodynamics; Hemofiltration; Humans; Male; Middle Aged; Prospective Studies; Renal Dialysis; Sepsis

In vitro and clinical studies using parenteral fosfomycin have suggested the possibility of using this drug against infections caused by MDR microorganisms. The aim of this study was to describe a case series of patients treated with fosfomycin who had severe infections caused by pan-drug-resistant Gram-negative bacteria.. We describe a prospective series of cases of hospitalized patients with infections caused by Gram-negative bacteria resistant to β-lactams and colistin, treated with 16 g of fosfomycin daily for 10-14 days. Isolates were tested for antimicrobial susceptibility and synergism of fosfomycin with meropenem. We tested for resistance genes and performed typing using PCR and WGS.. Thirteen patients received fosfomycin (seven immunosuppressed); they had bloodstream infections (n = 11; 85%), ventilator-associated pneumonia (n = 1; 8%) and surgical site infection (n = 1; 8%), caused by Klebsiella pneumoniae (n = 9), Serratia marcescens (n = 3) and Pseudomonas aeruginosa (n = 1). Overall, eight (62%) patients were cured. Using time-kill assays, synergism between fosfomycin and meropenem occurred in 9 (82%) of 11 isolates. Typing demonstrated that K. pneumoniae were polyclonal. Eight patients (62%) had possible adverse events, but therapy was not discontinued.. Fosfomycin may be safe and effective against infections caused by pan-drug-resistant Gram-negative microorganisms with different antimicrobial resistance mechanisms and there seems to be synergism with meropenem.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Drug Synergism; Drug-Related Side Effects and Adverse Reactions; Female; Fosfomycin; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Male; Meropenem; Microbial Sensitivity Tests; Microbial Viability; Middle Aged; Pneumonia, Ventilator-Associated; Sepsis; Surgical Wound Infection; Young Adult

Antimicrobial resistance (AMR) is of increasing global concern, threatening to undermine recent progress in reducing child and neonatal mortality. Repurposing older antimicrobials is a prominent strategy to combat multidrug-resistant sepsis. A potential agent is fosfomycin, however, there is scarce data regarding its in vitro activity and pharmacokinetics in the paediatric population.. We analysed a contemporary, systematically collected archive of community-acquired (CA) and hospital-acquired (HA) paediatric Gram-negative bacteraemia isolates for their susceptibility to fosfomcyin. MICs were determined using agar serial dilution methods and validated by disk diffusion testing where breakpoints are available. Disk diffusion antimicrobial susceptibility testing was also conducted for current empirical therapies (ampicillin, gentamicin, ceftriaxone) and amikacin (proposed in the literature as a new combination empirical therapeutic option).. Fosfomycin was highly active against invasive Gram-negative isolates, including 90  % (202/224) of Enterobacteriaceae and 96  % (22/23) of Pseudomonas spp. Fosfomycin showed high sensitivity against both CA isolates (94 %, 142/151) and HA isolates (81 %, 78/96; P =0.0015). CA isolates were significantly more likely to be susceptible to fosfomycin than the current first-line empirical therapy (96  % vs 59  %, P <0.0001). Extended spectrum β-lactamases (ESBL) production was detected in 34  % (85/247) of isolates with no significant difference in fosfomycin susceptibility between ESBL-positive or -negative isolates [73/85 (86  %) vs 147/162 (91  %) respectively, P =0.245]. All isolates were susceptible to a fosfomycin-amikacin combination.. Gram-negative paediatric bacteraemia isolates are highly susceptible to fosfomycin, which could be combined with aminoglycosides as a new, carbapenem-sparing regimen to achieve excellent coverage to treat antimicrobial-resistant neonatal and paediatric sepsis.

Topics: Anti-Bacterial Agents; Bacteremia; Child, Preschool; Community-Acquired Infections; Cross Infection; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli Infections; Female; Fosfomycin; Gram-Negative Bacteria; Humans; Infant; Infant, Newborn; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Pseudomonas; Sepsis

Fosfomycin has emerged as a potential therapy for multidrug-resistant bacterial infections. In most European countries, the oral formulation is only approved as a 3 g single dose for treatment of uncomplicated cystitis. However, for the treatment of complicated systemic infections, this dose regimen is unlikely to reach efficacious serum and tissue concentrations. This study aims to investigate different fosfomycin-dosing regimens to evaluate its rationale for treatment of systemic infections. Serum concentration-time profiles of fosfomycin were simulated using a population pharmacokinetic model based on published pharmacokinetic parameter values, their uncertainty, inter-individual variability and covariates. The model was validated on published data and used to simulate a wide range of dosing regimens for oral and intravenous administration of fosfomycin. Finally, based on the minimum inhibitory concentration for E. coli, surrogate pharmacodynamic indices were calculated for each dosing regimen. This is the first population pharmacokinetic model to describe the oral pharmacokinetics of fosfomycin using data from different literature sources. The model and surrogate pharmacodynamic indices provide quantitative evidence that a dosing regimen of 6-12 g per day divided in 3 doses is required to obtain efficacious exposure and may serve as a first step in the treatment of systemic multi-drug-resistant bacterial infections.

Topics: Administration, Oral; Anti-Bacterial Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance, Multiple, Bacterial; Escherichia coli; Feasibility Studies; Fosfomycin; Humans; Microbial Sensitivity Tests; Models, Biological; Sepsis; Treatment Outcome

Acute osteomyelitis of the clavicle accounts for less than 3% of osteomyelitis cases, with its usual location in the middle third. It may be hematogenous, due to contiguity, or secondary to catheterization of the subclavian vein or neck surgery. The diagnosis is often delayed, and clinical symptoms may simulate obstetric brachial plexus palsy in young children. We report a new case of osteomyelitis of the clavicle in a 30-day-old newborn.

Topics: Abscess; Administration, Oral; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Catheterization, Central Venous; Cefotaxime; Clavicle; Female; Fever of Unknown Origin; Follow-Up Studies; Fosfomycin; Fractures, Spontaneous; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Infusions, Intravenous; Male; Osteomyelitis; Pregnancy; Pregnancy Complications, Infectious; Radionuclide Imaging; Sepsis; Streptococcal Infections; Ultrasonography

A woman aged 56 years of age had a community-acquired left neck abscess and internal jugular vein thrombosis with septicemia due to extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae. Even though she was treated with intravenous meropenem, the bacteremia persisted. She was complicated with multiple brain abscesses, seizure, and leucopenia. After a combination of intravenous fosfomycin and meropenem, her clinical condition became stable. Combination treatment was continued for 2 months and she recovered. In individual cases of Lemierre syndrome with brain abscess caused by ESBL-producing Enterobacteriaceae, fosfomycin combination therapy may be the alternative choice.

Topics: Anti-Bacterial Agents; beta-Lactamases; Brain; Brain Abscess; Community-Acquired Infections; Drug Therapy, Combination; Female; Fosfomycin; Humans; Infusions, Intravenous; Klebsiella Infections; Klebsiella pneumoniae; Lemierre Syndrome; Meropenem; Middle Aged; Sepsis; Thienamycins; Tomography, X-Ray Computed; Treatment Outcome

Vancomycin is the drug of choice for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. However, vancomycin treatment failures are occasionally observed with some strains that are considered susceptible to vancomycin according to Clinical and Laboratory Standards Institute breakpoints (vancomycin minimum inhibitory concentration [MIC] < or =2 microg/mL). Although fosfomycin has in vitro activity against MRSA, clinical data regarding the use of fosfomycin either alone or in combination for the management of MRSA bacteremia is limited.. A 57-year-old woman who was on regular hemodialysis for chronic kidney disease presented with sepsis associated with possible infection of arteriovenous fistula. Blood culture grew MRSA with vancomycin MIC of 1.5 microg/mL. Despite placement of a double-lumen catheter for hemodialysis and treatment with vancomycin and serum concentrations monitoring to keep trough levels of 15 to 20 microg/mL, her blood cultures still continued to grow MRSA for over 10 days. Later intravenous fosfomycin was added to the regimen along with vancomycin. After three days of this combination, suppression of bacteremia was achieved.. Combination of fosfomycin and vancomycin might be another option for the treatment of bacteremia due to MRSA with vancomycin MIC of 1.5 microg/mL that is not responsive to vancomycin alone.

Topics: Anti-Bacterial Agents; Drug Therapy, Combination; Female; Fosfomycin; Humans; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Sepsis; Vancomycin

The present investigation explored the ability of fosfomycin to penetrate lung tissue of septic patients by utilizing the microdialysis technique.. After microdialysis probe insertion into healthy and infected lung tissue, a single intravenous dose of 4 g of fosfomycin was administered.. The mean C(max), T(max), AUC(0-4) and AUC(0-infinity) for healthy lung were 131.6 +/- 110.6 mg/L, 1.1 +/- 0.4 h, 242.4 +/- 101.6 mgxh/L and 367.6 +/- 111.9 mgxh/L, respectively. The corresponding values for infected lung were 107.5 +/- 60.2 mg/L, 1.4 +/- 0.5 h, 203.5 +/- 118.4 mgxh/L and 315.1 +/- 151.2 mgxh/L. The half-life of fosfomycin ranged from 2.2 to 2.7 h between compartments. The magnitude of lung tissue penetration, as determined by the ratios of the AUC(0-infinity) for lung to the AUC(0-infinity) for plasma, was 0.63 +/- 0.31 and 0.53 +/- 0.31 for healthy and infected lung, respectively.. We conclude that fosfomycin achieves antimicrobially effective concentrations in infected lung tissue.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Female; Fosfomycin; Half-Life; Humans; Injections, Intravenous; Lung; Male; Middle Aged; Sepsis

The supply of fosfomycin had to be carefully controlled over metropolitan France during 10 weeks because of a unique crisis in production. Three hundred and forty prescriptions were collected and re-examined by an expert committee. The main indications were osteoarthritis (27%), lung infections (21%), severe sepsis (12.5%), and urinary tract infections (11%). The main bacteria involved, often multidrug resistant, were Pseudomonas aeruginosa (40%) and methicillin-resistant Staphylococcus. A careful analysis of the antibiogram proved fosfomycin to be irreplaceable in 36% of the cases. This study confirms and specifies the interest of fosfomycin. To our knowledge, this study was a unique opportunity to collect such specific data from the whole of France over a two-month shortage period.

Topics: Anti-Infective Agents; Drug Prescriptions; Equipment and Supplies, Hospital; Fosfomycin; Humans; Lung Diseases; Medically Underserved Area; Methicillin Resistance; Osteoarthritis; Sepsis; Staphylococcal Infections

Topics: Anti-Bacterial Agents; Endotoxemia; Fosfomycin; Humans; Lipopolysaccharides; Male; Pilot Projects; Sepsis; Shock, Septic

A total of 15 patients with a variety of infectious disease were treated with fosfomycin in Chang Gung Memorial Hospital, Kaoshiung. The drug was administered by iv drip infusion in doses of 204g per day for 5-28 days. The clinical response was satisfactory in 6 (100%) of 6 patients with urinary tract infection, 8 (80%) of 10 with septicemia and 1 with pneumonia. Overall, fosfomycin was effective in 13 (86%) of all patients treated. Except for 1 isolate of the pathogen, B. fragilis, and another 1 isolate of oxacillin-resistant Staphylococcus aureus, all the other 16 pathogens isolated, including Escherichia coli, Aeromonas, Klebsiella. Staphylococcus aureus, Acinetobacter, and Pseudomonas aeruginosa were successfully eradicated. Only 1 case developed skin rash. So fosfomycin is a useful agent and gram (-) organisms including oxacillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa.

Topics: Adult; Aged; Bacterial Infections; Drug Evaluation; Female; Fosfomycin; Humans; Male; Middle Aged; Sepsis; Urinary Tract Infections

The pathophysiologic mechanism of acute hematogenous osteomyelitis in children has been further elucidated. Investigations revealed, that certain strains of staphylococcus aureus, responsible for the majority of infections, can resist intracellular killing after phagocytosis. Beta-lactam-antibiotics don't penetrate well into phagocytes and are unable to eradicate staphylococci surviving intracellularly. Fosfomycin, clindamycin and combinations of these antibiotics with beta-lactam-antibiotics are able to eradicate staphylococci also in phagocytic vacuoles. In a therapeutic investigation 36 patients have been treated with fosfomycin in combination with cefamandole intravenously for 10-14 days followed by clindamycin orally for 3-6 weeks. With this treatment schedule the therapeutic outcome was superior to previously employed therapeutic regimen.

Topics: Cefamandole; Child; Clindamycin; Drug Therapy, Combination; Fosfomycin; Humans; Macrophages; Osteomyelitis; Oxacillin; Phagocytosis; Sepsis; Staphylococcal Infections; Staphylococcus aureus

Topics: Aged; Aged, 80 and over; Arthritis, Infectious; Cloxacillin; Drug Resistance, Microbial; Female; Fosfomycin; Humans; Knee Joint; Lung Abscess; Methicillin; Minocycline; Sepsis; Staphylococcal Infections; Staphylococcus aureus

Topics: Cefotaxime; Child; Child, Preschool; Cross Infection; Female; Fosfomycin; Humans; Infant; Infant, Newborn; Intensive Care Units; Male; Sepsis; Staphylococcal Infections

Five hundred strains of methicillin-resistant Staphylococcus aureus were tested against various anti-staphylococcal agents. Vancomycin, fusidic acid and fosfomycin were found to be the most effective. Only 1 strain out of 500 was resistant to fosfomycin. Three patients with methicillin-resistant Staphylococcus aureus septicaemia were successfully treated by fosfomycin. We conclude that fosfomycin could be the drug of choice for methicillin-resistant Staphylococcus aureus infection.

Topics: Adult; Female; Fosfomycin; Humans; Male; Methicillin; Middle Aged; Penicillin Resistance; Sepsis; Staphylococcal Infections; Staphylococcus aureus

Topics: Anti-Bacterial Agents; Bacterial Infections; Blood; Cerebrospinal Fluid; Female; Flavobacterium; Fosfomycin; Humans; Infant; Meningitis; Sepsis

Topics: Anti-Bacterial Agents; Drug Tolerance; Fosfomycin; Humans; Kidney Failure, Chronic; Pseudomonas; Sepsis; Serratia

The clinical and bacteriological response of 38 treatments performed on 24 children (11 of them neonates) carrying out separate treatments with carbenicillin (2 treatments), gentamicin [4], fosfomycin [6], and associated treatments with gentamicin plus carbenicillin [6], fosfomycin plus gentamicin [18] and fosfomycin plus carbenicillin [2] are considered. The clinical cure was obtained in 21 children (87.5%). The most effective treatment was fosfomycin plus gentamicin; both antibiotics showed synergism in vitro on isolated Serratia strains. A dosage of 75 mg/kg fosfomycin enables serum levels of about 32 mug/ml during 4-5 h, being this level higher to the MIC of all isolated strains of S. marcescens.

Topics: Anti-Bacterial Agents; Carbenicillin; Drug Evaluation; Drug Therapy, Combination; Enterobacteriaceae Infections; Female; Fosfomycin; Gentamicins; Humans; Infant; Infant, Newborn; Male; Microbial Sensitivity Tests; Sepsis; Serratia marcescens

Here we present the results obtained in the treatment with fosfomycin of 58 patients of diverse obstetric-gynecological infections manifested by clinical symptomology and by the initial isolation of 70 strains of different germs, all of them sensitive to this antibiotic. The types of infections were urinary, abdominal wall, perennial septicemias, and endometritis; 45 of them motivated by or resulting from pregnancy, and the remaining 13 from gynecological causes. The most frequent treatment was 1 g/6h during 10 days, using sodium salt intramuscularly in 33 cases, and calcium salt taken orally in 26. The clinical results were good in 50 cases (86.2%) with improvement in 3 (5.1%) and persistency of the infection in 5. The bacteriological evolution was good on 34 occasions (58.6%), partial in 4 (6.8%), and poor in 6 (10.3%). In 14 cases no control could be made since the wound healed. The tolerance to the antibiotic was good and no manifestations of toxicity were observed.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Drug Evaluation; Endometritis; Female; Fosfomycin; Genital Diseases, Female; Humans; Injections, Intramuscular; Middle Aged; Sepsis; Urinary Tract Infections

Topics: Ampicillin; Anti-Bacterial Agents; Carbenicillin; Cephalosporins; Chloramphenicol; Cloxacillin; Fosfomycin; Gentamicins; Haemophilus Infections; Humans; Methicillin; Penicillin G; Polymyxins; Pseudomonas Infections; Respiratory Tract Infections; Sepsis; Staphylococcal Infections; Streptococcal Infections