fosfomycin and Bacteremia

There is growing concern regarding the increased resistance rates of numerous pathogens and the limited availability of new antibiotics against these pathogens. In this context, fosfomycin is of considerable interest due to its activity against a wide spectrum of these microorganisms. We will review the encouraging data on this issue regarding the use of fosfomycin in treating Gram-negative bacterial infections. We will also cover fosfomycin's role against 2 of the main causal agents of bacteremia and endocarditis worldwide (nosocomial and community-acquired): enterococci, whose growing resistance to glycopeptides and aminoglycosides represents a serious threat, and methicillin-resistant Staphylococcus aureus, whose infection, despite efforts, continues to be associated with high morbidity and mortality and a high risk of complications. Thanks also to its considerable synergistic capacity with various antibiotics, fosfomycin is a tool for extending the therapeutic arsenal against these types of infections.

Topics: Animals; Anti-Bacterial Agents; Bacteremia; Endocarditis, Bacterial; Evidence-Based Medicine; Fosfomycin; Humans

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

Case-fatality rates for Staphylococcus aureus bacteremia (SAB) remain unacceptably high and have improved only modestly in recent decades. Treatment of SAB is still a clinical challenge, especially if methicillin-resistant strains are involved. New drugs with anti-staphylococcal activity are currently available, and their role as alternatives to standard therapies is being investigated. Areas covered: In this review, we give an update of the current available antibiotics for the treatment of SAB. We provide information regarding the pharmacological characteristics, the accepted indications, and the most important adverse events of the old and new anti-staphylococcal agents, as well as the existing evidence on their use for the treatment of SAB. Expert opinion: The management of patients with SAB is very complex and needs a multidisciplinary approach. There are currently new available options for the treatment of methicillin-resistant SAB. However, more data from clinical trials are needed to assign specific roles to each antibiotic and to include them in the new antibacterial armamentarium. The role of combination therapy for the treatment of increasingly complex patients with SAB deserves thorough investigation.

Topics: Anti-Bacterial Agents; Bacteremia; Cefazolin; Cephalosporins; Drug Therapy, Combination; Fosfomycin; Glycopeptides; Humans; Methicillin-Resistant Staphylococcus aureus; Penicillins; Staphylococcal Infections; Staphylococcus aureus

Carbapenem-resistant Acinetobacter baumannii (CRAB) constitutes an increasing problem worldwide. CRAB bacteremia is associated with a high fatality rate and its optimal treatment has not been established. Early institution of appropriate therapy is shown to improve survival of patients with CRAB bloodstream infection. Regrettably, treatment options are limited. Little information exists about the efficacy of sulbactam for the treatment of CRAB bacteremia. Colistin and tigecycline possess good in vitro activity and represent in many cases the only therapeutic options although clinical data are scarce. The need for a loading dose of colistin has been recently demonstrated to rapidly achieve therapeutic levels. The use of combination therapy is also a matter of debate but current evidence do not support its routine use.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; Carbapenems; Colistin; Drug Synergism; Drug Therapy, Combination; Fosfomycin; Humans; Microbial Sensitivity Tests; Minocycline; Polymyxins; Sulbactam; Tigecycline

Topics: Animals; Anti-Allergic Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Bacteremia; Bacteria; Biofilms; Fosfomycin; Humans; Kidney; Kidney Diseases; Lymphocytes; Lysosomes; Molecular Mimicry; Neutrophils; Pseudomonas Infections

Treatment failure occurs in about 25% of patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. We assessed whether cloxacillin plus fosfomycin achieves better treatment success than cloxacillin alone in hospitalized adults with MSSA bacteremia. We conducted a multicenter, open-label, phase III-IV superiority randomized clinical trial. We randomly assigned patients (1:1) to receive 2 g of intravenous cloxacillin alone every 4 h or with 3 g of intravenous fosfomycin every 6 h for the initial 7 days. The primary endpoint was treatment success at day 7, a composite endpoint with the following criteria: patient alive, stable or with improved quick Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA, adjudicated by an independent committee blinded to treatment allocation. We randomized 215 patients, of whom 105 received cloxacillin plus fosfomycin and 110 received cloxacillin alone. We analyzed the primary endpoint with the intention-to-treat approach in 214 patients who received at least 1 day of treatment. Treatment success at day 7 after randomization was achieved in 83 (79.8%) of 104 patients receiving combination treatment versus 82 (74.5%) of 110 patients receiving monotherapy (risk difference 5.3%; 95% confidence interval (CI), -5.95-16.48). Secondary endpoints, including mortality and adverse events, were similar in the two groups except for persistent bacteremia at day 3, which was less common in the combination arm. In a prespecified interim analysis, the independent committee recommended stopping recruitment for futility prior to meeting the planned randomization of 366 patients. Cloxacillin plus fosfomycin did not achieve better treatment success at day 7 of therapy than cloxacillin alone in MSSA bacteremia. Further trials should consider the intrinsic heterogeneity of the infection by using a more personalized approach. ClinicalTrials.gov registration: NCT03959345 .

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Cloxacillin; Drug Therapy, Combination; Fosfomycin; Humans; Methicillin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome

The consumption of broad-spectrum drugs has increased as a consequence of the spread of multidrug-resistant (MDR) Escherichia coli. Finding alternatives for these infections is critical, for which some neglected drugs may be an option.. To determine whether fosfomycin is noninferior to ceftriaxone or meropenem in the targeted treatment of bacteremic urinary tract infections (bUTIs) due to MDR E coli.. This multicenter, randomized, pragmatic, open clinical trial was conducted at 22 Spanish hospitals from June 2014 to December 2018. Eligible participants were adult patients with bacteremic urinary tract infections due to MDR E coli; 161 of 1578 screened patients were randomized and followed up for 60 days. Data were analyzed in May 2021.. Patients were randomized 1 to 1 to receive intravenous fosfomycin disodium at 4 g every 6 hours (70 participants) or a comparator (ceftriaxone or meropenem if resistant; 73 participants) with the option to switch to oral fosfomycin trometamol for the fosfomycin group or an active oral drug or parenteral ertapenem for the comparator group after 4 days.. The primary outcome was clinical and microbiological cure (CMC) 5 to 7 days after finalization of treatment; a noninferiority margin of 7% was considered.. Among 143 patients in the modified intention-to-treat population (median [IQR] age, 72 [62-81] years; 73 [51.0%] women), 48 of 70 patients (68.6%) treated with fosfomycin and 57 of 73 patients (78.1%) treated with comparators reached CMC (risk difference, -9.4 percentage points; 1-sided 95% CI, -21.5 to ∞ percentage points; P = .10). While clinical or microbiological failure occurred among 10 patients (14.3%) treated with fosfomycin and 14 patients (19.7%) treated with comparators (risk difference, -5.4 percentage points; 1-sided 95% CI, -∞ to 4.9; percentage points; P = .19), an increased rate of adverse event-related discontinuations occurred with fosfomycin vs comparators (6 discontinuations [8.5%] vs 0 discontinuations; P = .006). In an exploratory analysis among a subset of 38 patients who underwent rectal colonization studies, patients treated with fosfomycin acquired a new ceftriaxone-resistant or meropenem-resistant gram-negative bacteria at a decreased rate compared with patients treated with comparators (0 of 21 patients vs 4 of 17 patients [23.5%]; 1-sided P = .01).. This study found that fosfomycin did not demonstrate noninferiority to comparators as targeted treatment of bUTI from MDR E coli; this was due to an increased rate of adverse event-related discontinuations. This finding suggests that fosfomycin may be considered for selected patients with these infections.. ClinicalTrials.gov Identifier: NCT02142751.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Fosfomycin; Humans; Male; Middle Aged; Spain

We aimed to determine whether daptomycin plus fosfomycin provides higher treatment success than daptomycin alone for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and endocarditis.. A randomized (1:1) phase 3 superiority, open-label, and parallel group clinical trial of adult inpatients with MRSA bacteremia was conducted at 18 Spanish hospitals. Patients were randomly assigned to receive either 10 mg/kg of daptomycin intravenously daily plus 2 g of fosfomycin intravenously every 6 hours, or 10 mg/kg of daptomycin intravenously daily. Primary endpoint was treatment success 6 weeks after the end of therapy.. Of 167 patients randomized, 155 completed the trial and were assessed for the primary endpoint. Treatment success at 6 weeks after the end of therapy was achieved in 40 of 74 patients who received daptomycin plus fosfomycin and in 34 of 81 patients who were given daptomycin alone (54.1% vs 42.0%; relative risk, 1.29 [95% confidence interval, .93-1.8]; P = .135). At 6 weeks, daptomycin plus fosfomycin was associated with lower microbiologic failure (0 vs 9 patients; P = .003) and lower complicated bacteremia (16.2% vs 32.1%; P = .022). Adverse events leading to treatment discontinuation occurred in 13 of 74 patients (17.6%) receiving daptomycin plus fosfomycin, and in 4 of 81 patients (4.9%) receiving daptomycin alone (P = .018).. Daptomycin plus fosfomycin provided 12% higher rate of treatment success than daptomycin alone, but this difference did not reach statistical significance. This antibiotic combination prevented microbiological failure and complicated bacteremia, but it was more often associated with adverse events.. NCT01898338.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Daptomycin; Endocarditis; Fosfomycin; Humans; Methicillin-Resistant Staphylococcus aureus; Staphylococcal Infections; Treatment Outcome

Methicillin-susceptible. We will perform a superiority, randomised, open-label, phase IV-III, two-armed parallel group (1:1) clinical trial at 20 Spanish tertiary hospitals. Adults (≥18 years) with isolation of MSSA from at least one blood culture ≤72 hours before inclusion with evidence of infection, will be randomly allocated to receive either cloxacillin 2 g/4-hour intravenous plus fosfomycin 3 g/6-hour intravenous or cloxacillin 2 g/4-hour intravenous alone for 7 days. After the first week, sequential treatment and total duration of antibiotic therapy will be determined according to clinical criteria by the attending physician.Primary endpoints: (1) Treatment success at day 7, a composite endpoint comprising all the following criteria: patient alive, stable or with improved quick-Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA at day 7. (2) Treatment success at test of cure (TOC) visit: patient alive and no isolation of MSSA in blood culture or at another sterile site from day 8 until TOC (12 weeks after randomisation).We assume a rate of treatment success of 74% in the cloxacillin group. Accepting alpha risk of 0.05 and beta risk of 0.2 in a two-sided test, 183 subjects will be required in each of the control and experimental groups to obtain statistically significant difference of 12% (considered clinically significant).. Ethical approval has been obtained from the Ethics Committee of Bellvitge University Hospital (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), and is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders.. The protocol has been approved by AEMPS with the Trial Registration Number EudraCT 2018-001207-37. ClinicalTrials.gov Identifier: NCT03959345; Pre-results.

Topics: Adult; Bacteremia; Cloxacillin; Fosfomycin; Humans; Methicillin; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Safrole; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome

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

To compare efficacy, safety, and cost-effectiveness of fosfomycin tromethamine with other standard-of-care antibiotics in patients undergoing ureteroscopic lithotripsy.. This study was a prospective, multicenter, randomized, controlled trial. Eligible patients scheduled for ureteroscopic lithotripsy were randomly assigned to receive either fosfomycin (fosfomycin group, N = 101 patients) or standard-of-care antibiotic therapy as prophylaxis (control group, N = 115 patients). The incidence of infectious complications and adverse events was analyzed between the two groups, as well as the cost-benefit analysis.. The incidence of infections following lithotripsy was 3.0% in the fosfomycin group and 6.1% in the control group (p > 0.05). Only asymptomatic bacteriuria was reported in fosfomycin group. In the control group was reported asymptomatic bacteriuria (3.5%), fever (0.9%), bacteremia (0.9%), and genitourinary infection (0.9%). The rate of adverse events was very low, with no adverse event reported in the fosfomycin group and only one in the control group (forearm phlebitis). The average cost per patient of antibiotic therapy with fosfomycin was 151.45 ± 8.62 yuan (22.7 ± 1.3 USD), significantly lower compared to the average cost per patient of antibiotics used in the control group 305.10 ± 245.95 yuan (45.7 ± 36.9 USD; p < 0.001).. Two oral doses of 3 g fosfomycin tromethamine showed good efficacy and safety and low cost in perioperative prophylaxis of infections following ureteroscopic stone removal.

Topics: Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacteremia; Bacteriuria; Cost-Benefit Analysis; Female; Fever; Fosfomycin; Humans; Lithotripsy; Male; Middle Aged; Perioperative Care; Prospective Studies; Standard of Care; Ureteral Calculi; Ureteroscopy

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Endocarditis; Female; Fosfomycin; Humans; Imipenem; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Treatment Outcome; Vancomycin

Despite the availability of new antibiotics such as daptomycin, methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia continues to be associated with high clinical failure rates. Combination therapy has been proposed as an alternative to improve outcomes but there is a lack of clinical studies. The study aims to demonstrate that combination of daptomycin plus fosfomycin achieves higher clinical success rates in the treatment of MRSA bacteraemia than daptomycin alone.. A multicentre open-label, randomised phase III study. Adult patients hospitalised with MRSA bacteraemia will be randomly assigned (1:1) to group 1: daptomycin 10 mg/kg/24 h intravenous; or group 2: daptomycin 10 mg/kg/24 h intravenous plus fosfomycin 2 gr/6 g intravenous. The main outcome will be treatment response at week 6 after stopping therapy (test-of-cure (TOC) visit). This is a composite variable with two values: Treatment success: resolution of clinical signs and symptoms (clinical success) and negative blood cultures (microbiological success) at the TOC visit. Treatment failure: if any of the following conditions apply: (1) lack of clinical improvement at 72 h or more after starting therapy; (2) persistent bacteraemia (positive blood cultures on day 7); (3) therapy is discontinued early due to adverse effects or for some other reason based on clinical judgement; (4) relapse of MRSA bacteraemia before the TOC visit; (5) death for any reason before the TOC visit. Assuming a 60% cure rate with daptomycin and a 20% difference in cure rates between the two groups, 103 patients will be needed for each group (α:0.05, ß: 0.2). Statistical analysis will be based on intention to treat, as well as per protocol and safety analysis.. The protocol was approved by the Spanish Medicines and Healthcare Products Regulatory Agency (AEMPS). The sponsor commits itself to publishing the data in first quartile peer-review journals within 12 months of the completion of the study.. NCT01898338.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Bacteremia; Daptomycin; Drug Combinations; Fosfomycin; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Research Design; Staphylococcal Infections; Treatment Outcome

There is an urgent need for alternative rescue therapies in invasive infections caused by methicillin-resistant Staphylococcus aureus (MRSA). We assessed the clinical efficacy and safety of the combination of fosfomycin and imipenem as rescue therapy for MRSA infective endocarditis and complicated bacteremia.. The trial was conducted between 2001 and 2010 in 3 Spanish hospitals. Adult patients with complicated MRSA bacteremia or endocarditis requiring rescue therapy were eligible for the study. Treatment with fosfomycin (2 g/6 hours IV) plus imipenem (1 g/6 hours IV) was started and monitored. The primary efficacy endpoints were percentage of sterile blood cultures at 72 hours and clinical success rate assessed at the test-of-cure visit (45 days after the end of therapy).. The combination was administered in 12 patients with endocarditis, 2 with vascular graft infection, and 2 with complicated bacteremia. Therapy had previously failed with vancomycin in 9 patients, daptomycin in 2, and sequential antibiotics in 5. Blood cultures were negative 72 hours after the first dose of the combination in all cases. The success rate was 69%, and only 1 of 5 deaths was related to the MRSA infection. Although the combination was safe in most patients (94%), a patient with liver cirrhosis died of multiorgan failure secondary to sodium overload. There were no episodes of breakthrough bacteremia or relapse.. Fosfomycin plus imipenem was an effective and safe combination when used as rescue therapy for complicated MRSA bloodstream infections and deserves further clinical evaluation as initial therapy in these infections.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Blood; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Endocarditis, Bacterial; Female; Fosfomycin; Humans; Imipenem; Infusions, Intravenous; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Salvage Therapy; Spain; Staphylococcal Infections; Treatment Outcome

The aim of the study was to evaluate clinical and microbiological efficacy and safety of intravenous fosfomycin for the treatment of carbapenem-resistant

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Fosfomycin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Pneumonia; Urinary Tract Infections

Ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) in patients hospitalized in intensive care units (ICUs) is an important and challenging complication, including in patients with coronavirus disease 2019 (COVID-19). Considering the poor lung penetration of most antibiotics, including intravenous colistin due to the poor pharmacokinetics/pharmacodynamics at the infection site, the choice of the best antibiotic regimen is still being debated.. This single-centre, observational study was conducted from March 2020 to August 2022, and included all patients hospitalized consecutively with VAP and concomitant bloodstream infection due to CRAB in the COVID-ICU. The main goal of the study was to evaluate risk factors associated with survival or death at 30 days from VAP onset. A propensity score for receiving therapy was added to the model.. During the study period, 73 patients who developed VAP and concomitant positive blood cultures caused by CRAB were enrolled in the COVID-ICU. Of these patients, 67 (91.7%) developed septic shock, 42 (57.5%) had died at 14 days and 59 (80.8%) had died at 30 days. Overall, 54 (74%) patients were treated with a colistin-containing regimen and 19 (26%) were treated with a cefiderocol-containing regimen. Cox regression analysis showed that chronic obstructive pulmonary disease and age were independently associated with 30-day mortality. Conversely, cefiderocol-containing regimens and cefiderocol + fosfomycin in combination were independently associated with 30-day survival, as confirmed by propensity score analysis.. This real-life study in patients with bacteraemic VAP caused by CRAB provides useful suggestions for clinicians, showing a possible benefit of cefiderocol and its association with fosfomycin.

Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Bacteremia; Carbapenems; Cefiderocol; Colistin; COVID-19; Fosfomycin; Humans; Pneumonia, Ventilator-Associated

Topics: Anti-Bacterial Agents; Bacteremia; Fosfomycin; Gram-Positive Bacterial Infections; Humans; Salvage Therapy; Vancomycin

Synergistic combinations of daptomycin and β-lactam antibiotics are currently recommended for treatment of VRE bloodstream infection (BSI). The efficacy of these combinations is jeopardized by VRE inherently resistant to β-lactam antibiotics. The combination of daptomycin and fosfomycin is recommended as an alternative therapy for VRE BSI; however, clinical data to support use of this combination are lacking.. We conducted a prospective observational multicentre study of patients treated with a combination of daptomycin and fosfomycin for VRE BSI during 2016-20. The primary outcome was 28 day mortality. Multivariable logistic regression was performed for outcome analysis.. The study included 106 patients from 1112 VRE BSI episodes. The overall 28 day mortality was 40.6%. The median (IQR) daptomycin dose was 10.18 mg/kg (9.43-10.70). The fosfomycin dose was 16 g/day (8-22.5). Ninety-six isolates were available for MIC testing. The fosfomycin MIC was 32 mg/L in 6 (6.3%), 64 mg/L in 68 (70.8%) and ≥128 mg/L in 22 (22.9%) isolates. Independent of Charlson comorbidity index and Pitt bacteraemia score, fosfomycin MIC ≥128 mg/L [adjusted OR (aOR) = 3.05; 95% CI = 1.01-9.19; P = 0.047] and daptomycin dose (aOR = 0.64; 95% CI = 0.43-0.97; P = 0.04) predicted mortality.. Higher daptomycin dose and susceptibility to fosfomycin were independently associated with lower mortality in patients with VRE BSI. Our results suggest that higher doses of daptomycin are indicated for VRE BSI, whether or not it is used in combination with fosfomycin. The combination was less effective for patients with fosfomycin-resistant isolates.

Topics: Anti-Bacterial Agents; Bacteremia; Daptomycin; Enterococcus faecium; Fosfomycin; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Monobactams; Prospective Studies; Vancomycin; Vancomycin-Resistant Enterococci

Topics: Bacteremia; Beauty; Daptomycin; Endocarditis; Fosfomycin; Humans; Methicillin-Resistant Staphylococcus aureus

Topics: Bacteremia; beta-Lactamases; Fosfomycin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem

To investigate whether Staphylococcus aureus bloodstream infection (SAB) patients at high risk for complications or relapse benefit from combination therapy with adjunctive rifampicin or fosfomycin.. In this post hoc analysis, SAB patients with native valve infective endocarditis, osteoarticular infections or implanted foreign devices were included. The co-primary endpoints were all-cause 90 day mortality and death or SAB-related late complications within 180 days. To overcome treatment selection bias and account for its time dependence, inverse probability of treatment weights were calculated and included in marginal structural Cox proportional hazard models (MSCMs).. A total of 578 patients were included in the analysis, of which 313 (54%) received combination therapy with either rifampicin (n = 242) or fosfomycin (n = 58). In the multivariable MSCM, combination therapy was associated with a better outcome, that is, a lower rate of death or SAB-related late complications within 180 days (HR 0.65, 95% CI 0.46-0.92). This beneficial effect was primarily seen in patients with implanted foreign devices, in which combination therapy was associated with a lower rate of death or SAB-related late complications within 180 days (HR 0.53, 95% CI 0.35-0.79) and a lower 90 day mortality (HR 0.57, 95% CI 0.36-0.91). Upon agent-specific stratification, we found no significant differences in outcomes between combination therapy containing rifampicin and fosfomycin; however, the number of patients in most subgroups was not large enough to draw firm conclusions.. In patients with implanted foreign devices, combination therapy was associated with a better long-term outcome. Larger prospective studies are needed to validate these findings.

Topics: Anti-Bacterial Agents; Bacteremia; Fosfomycin; Humans; Prospective Studies; Recurrence; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Fosfomycin; Gene Transfer, Horizontal; Humans; Microbial Sensitivity Tests; Symbiosis

Rates of infection following transrectal ultrasound-guided prostate biopsy (TRUSPB) are increasing. The aim of this study was to evaluate the effectiveness of fosfomycin tromethamine (FMT) prophylaxis in preventing post-TRUSPB infectious complications.. This nested case-control study included patients undergoing TRUSPB in a Canadian tertiary-care hospital who developed post-TRUSPB bacteraemia or urinary tract infection. Four prophylaxis periods were defined: (i) ciprofloxacin, low-resistance period (CIPRO-LOW), 2002-2009; (ii) ciprofloxacin, high-resistance period (CIPRO-HIGH), 2010-October 2013; (iii) oral FMT, one dose (FOSFO1), December 2013-September 2015; and (iv) oral FMT, two doses (FOSFO2), November 2015-June 2016. Incidence rates of the infection were calculated.. TRUSPB (n=9391) resulted in 138 cases of urinary sepsis (58% with bacteraemia). The incidence rates were 1.8% (CIPRO-HIGH), 3.5% (FOSFO1; P=0.004 vs. CIPRO-HIGH) and 2.7% (FOSFO2; P=0.19 vs. CIPRO-HIGH). Although Escherichia coli remained the predominant pathogen with fosfomycin-based regimens, the proportion of infections caused by Klebsiella spp. was higher (20/66; 30.3%) than with ciprofloxacin-based regimens (2/77; 2.6%; P<0.0001).. Independent risk factors for infection were the prophylactic regimen administered, presence of urological co-morbidities and diabetes. FMT was therefore not an effective alternative to ciprofloxacin for preventing post-TRUSPB urinary sepsis. These results highlight the need for novel antibacterial prophylaxis approaches.

Topics: Aged; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacteremia; Bacteria; Biopsy, Needle; Canada; Case-Control Studies; Fosfomycin; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Prospective Studies; Prostate; Tertiary Care Centers; Urinary Tract Infections

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

An 85-year-old female presented with fever and consciousness disturbance for 3 days. The patient's blood culture subsequently revealed persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia despite the administration of vancomycin or teicoplanin monotherapy. Gallium inflammation scan and magnetic resonance image of the spine disclosed osteomyelitis and discitis at the level of L4-5. Surgical debridement was not feasible in this debilitated patient. Because of the creeping minimal inhibitory concentration of vancomycin of the causative isolate (1.5 μg/mL) and clinical failure with glycopeptide monotherapy, we changed the antibiotic therapy to a fosfomycin and teicoplanin combination therapy. The patient showed improved clinical response in terms of her enhanced consciousness as well as subsidence of persisted bacteremia. Despite the potential side effects of fosfomycin (such as diarrhea and hypernatremia), it combined with a glycopeptide may be an alternative therapy for invasive refractory MRSA infections.

Topics: Aged, 80 and over; Bacteremia; Drug Combinations; Female; Fosfomycin; Humans; Magnetic Resonance Imaging; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Osteomyelitis; Spine; Staphylococcal Infections; Teicoplanin; Vancomycin; Vancomycin Resistance

Topics: Aged; Amikacin; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Coinfection; Fosfomycin; Humans; Klebsiella Infections; Klebsiella oxytoca; Male; Methicillin Resistance; Staphylococcal Infections; Staphylococcus epidermidis; Treatment Outcome; Vancomycin

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Fosfomycin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male

Topics: Administration, Intravenous; Anti-Bacterial Agents; Bacteremia; Fatal Outcome; Fosfomycin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Liver Transplantation; Middle Aged; United States

Topics: Anti-Bacterial Agents; Bacteremia; Bacteriuria; Brazil; Drug Resistance, Bacterial; Fosfomycin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Linear Models; Meropenem; Microbial Sensitivity Tests; Rectum; Thienamycins

A total of 1878 non-duplicate clinical Escherichia coli isolates (comprising 1711 urinary isolates and 167 blood-culture isolates), which were collected from multiple centres in Hong Kong during 1996-2008, were used to investigate the prevalence and molecular epidemiology of plasmid-mediated fosfomycin (fos) resistance genes. Eighteen of the 1878 clinical E. coli isolates were fosfomycin resistant, of which six were fosA3 positive and two were positive for another fosA variant (designated fosKP96). No isolates had the fosC2 gene. The clones of the eight isolates were diverse: sequence type (ST) 95 (n = 2), ST118 (n = 1), ST131 (n = 1), ST617 (n = 1), ST648 (n = 1), ST1488 (n = 1) and ST2847 (n = 1). In the isolates, fosA3 and blaCTX-M genes were co-harboured on conjugative plasmids with F2:A-:B- (n = 2), N (n = 1), F-:A-:B1 and N (n = 1) and untypable (n = 2) replicons. Both fosKP96-carrying plasmids belonged to replicon N. RFLP analysis showed that the two F2:A-:B- plasmids carrying fosA3 and blaCTX-M-3 genes shared the same pattern. Complete sequencing of one of the two F2:A-:B- plasmids, pFOS-HK151325 (69 768 bp) demonstrated it to be >99 % identical to the previously sequenced plasmid pHK23a originating from a pig E. coli isolate in the same region. This study demonstrated the dissemination of fosA3 genes in diverse E. coli clones on multiple blaCTX-M-carrying plasmid types, of which F2:A-:B- plasmids closely related to pHK23a were shared by isolates from human and animal sources.

Topics: Animals; Anti-Bacterial Agents; Bacteremia; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Genes, Bacterial; Hong Kong; Humans; Molecular Epidemiology; Multilocus Sequence Typing; Plasmids; Prevalence; Sequence Homology; Swine; Urinary Tract Infections

Topics: Anti-Bacterial Agents; Bacteremia; Drug Resistance, Bacterial; Fosfomycin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests

The objective of this study was to evaluate the in vitro and in vivo efficacies of therapies including fosfomycin against clinical Staphylococcus aureus isolates with reduced susceptibility to vancomycin (hGISA). Time-kill curves were performed over 24 h. Peritonitis in C57BL/6 mice was induced by intraperitoneal inoculation of 10(8) CFU/ml. Four hours later (0 h), therapy was started and the treatment groups were: control (not treated), fosfomycin (100 mg/kg/5 h), vancomycin (60 mg/kg/5 h), imipenem (30 mg/kg/5 h), fosfomycin plus linezolid, fosfomycin plus vancomycin and fosfomycin plus imipenem, receiving subcutaneous therapy over 25 h. Bacterial counts in peritoneal fluid, bacteraemia and mortality rates were determined. In vitro, fosfomycin showed a synergistic effect when combined with the other antimicrobials tested. In the animal model, fosfomycin combinations were effective and significantly reduced the bacteraemia rates achieved in the control, imipenem and vancomycin groups (p < 0.05). The best combination in vivo was fosfomycin plus imipenem. Also, fosfomycin plus linezolid was significantly better than vancomycin alone, reducing the bacterial concentration in the peritoneal fluid. In conclusion, in vitro and in vivo, fosfomycin in combination with linezolid, vancomycin or imipenem exerted a good activity. Fosfomycin plus imipenem was the most active combination, decreasing 3 log CFU/ml, and appears to be a promising combination for clinical practice.

Topics: Acetamides; Animals; Anti-Bacterial Agents; Ascitic Fluid; Bacteremia; Bacterial Load; Disease Models, Animal; Drug Therapy, Combination; Female; Fosfomycin; Humans; Imipenem; Linezolid; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Oxazolidinones; Peritonitis; Staphylococcal Infections; Treatment Outcome; Vancomycin

It was reported that some methicillin-resistant Staphylococcus aureus (MRSA) show resistance to vancomycin (VCM) and beta-lactam antibiotics; thus, they are termed beta-lactam antibiotic-induced VCM-resistant MRSA (BIVR). The VCM resistance of MRSA is induced by the administration of beta-lactam antibiotics, but this phenomenon can be difficult to detect in the clinical laboratory. We detected the BIVR strain in a 64-year-old man who had had a ventilator tube inserted directly into the windpipe during long-term VCM therapy. The patient was diagnosed with MRSA pneumonia and septicemia on July 5, 2007, and sulbactam/ampicillin (SBT/ABPC) was administered for 5 days. However, the fever recurred, and administration of VCM was resumed for 7 days from July 19. Fever developed again, and VCM was administered again for 14 days from September 30. BIVR and VCM-low-sensitive MRSA were isolated from blood on October 18 and 22, although the VCM trough concentration was 10.2 microg/ml. On October 27, we changed to a combination of fosfomycin (FOM) and arbekacin (ABK), and thereafter the fever quickly decreased and the clinical symptoms abated. We isolated five MRSA strains from the blood of the patient, three strains of VCM-sensitive MRSA, one strain of BIVR, and one strain of a VCM-low-sensitive MRSA. The DNA band patterns determined by pulsed-field gel electrophoresis were completely identical except for the VCM-low-sensitive MRSA, which was missing one band. Furthermore, the VCM-low-sensitive MRSA became sensitive to beta-lactam antibiotics. Our results indicate the possibility that long-term VCM therapy is one of the factors that allow BIVR or VCM-low-sensitive MRSA to emerge, and this allows VCM therapy for MRSA to fail.

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; beta-Lactams; Dibekacin; Drug Therapy, Combination; Fosfomycin; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Pneumonia, Bacterial; Staphylococcal Infections; Time Factors; Vancomycin; Vancomycin Resistance

Multi-resistant coagulase-negative staphylococci (CNS) may cause systemic infections in patients undergoing bone marrow transplantation. Daptomycin, a new lipopeptide, and tigecycline, a new glycylcycline, have excellent activity against Gram-positive bacteria including methicillin-resistant staphylococci. This study presents the in vitro activity of daptomycin and tigecycline compared to vancomycin and fosfomycin against 105 CNS isolated from 76 bone marrow transplant patients with symptomatic bacteremia.. Blood stream isolates of Staphylococcus epidermidis (n = 102) and Staphylococcus haemolyticus (n = 3) from bone marrow transplant patients were collected from 2000 to 2006. The susceptibility of all isolates was tested using methods of the Clinical Laboratory Standards Institute.. The minimal inhibitory concentrations MIC(50) and MIC(90) were 0.125 microg/mL and 0.25 microg/mL for daptomycin, 0.25 and 0.5 microg/mL for tigecycline, 1 microg/mL and 2 microg/mL for vancomycin, and 8 microg/mL and >256 microg/mL for fosfomycin, respectively. MIC values of tested agents were similar for both methicillin-sensitive and methicillin-resistant S. epidermidis strains.. All CNS isolates were susceptible to the new antistaphylococcal agents daptomycin and tigecycline. Although vancomycin had been used over the past 30 yr at our bone marrow transplant unit all CNS were still susceptible to vancomycin.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Bone Marrow Transplantation; Coagulase; Daptomycin; Drug Resistance, Multiple, Bacterial; Female; Fosfomycin; Hematologic Neoplasms; Humans; In Vitro Techniques; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Staphylococcal Infections; Staphylococcus; Staphylococcus epidermidis; Staphylococcus haemolyticus; Tigecycline; Vancomycin

Fosfomycin is a molecule that inhibits the early stage of peptidoglycan synthesis and shows a broad-spectrum bactericidal activity against Gram-positive and Gram-negative bacteria. Using the Killing-curve method, we tested the in vitro bactericidal activity of fosfomycin alone or in combination with vancomycin or teicoplanin at a concentration of 8 microg/mL, that is easily achievable in serum at standard dosing regimens, against seven methicillin-resistant Staphylococcus aureus strains, isolated from patients with well documented device-associated infections unresponsive to or relapsing after glycopeptide therapy. MICs of vancomycin ranged from 1 to 4 microg/mL, MICs of teicoplanin from 2 to 8 microg/mL; MICs of fosfomycin were 8 microg/mL for two strains and >128 microg/mL for the remaining strains. The seven strains proved tolerant when tested for vancomycin and teicoplanin used alone at 2x MIC concentration. Fosfomycin was bactericidal (reduction of 2 log of the inoculum) only against the two susceptible strains. In all cases both vancomycin and teicoplanin in combination with fosfomycin developed bactericidal synergism already at a concentration of 1x MIC. If these results are confirmed by in vivo experiments, the combination of fosfomycin with glycopeptides might be useful for treating device-associated infections, and in preventing the phenomenon of increasing MICs for glycopeptides.

Topics: Anti-Bacterial Agents; Bacteremia; Blood Vessel Prosthesis; Catheterization; Device Removal; Drainage; Drug Evaluation, Preclinical; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Drug Synergism; Electrophoresis, Gel, Pulsed-Field; Equipment Contamination; Fosfomycin; Glycopeptides; Humans; Mediastinitis; Methicillin Resistance; Pacemaker, Artificial; Postoperative Complications; Prosthesis-Related Infections; Staphylococcal Infections; Staphylococcus aureus; Teicoplanin; Vancomycin

At our institution there has been a dichotomous antimicrobial treatment behaviour for acute haematogenous osteomyelitis (AHOM) since 1984. The surgical department favoured fosfomycin as initial choice and the medical department beta lactams. We aimed to compare the performance of both strategies.. Data from patients discharged with the diagnosis of AHOM between January 1984 and January 1998 were gathered from the charts by means of a questionnaire. Patients receiving fosfomycin treatment (FT) were compared with those receiving fosfomycin plus other antimicrobials (FT+) and those receiving no fosfomycin treatment (NFT).. A total of 103 patients aged 0.1-15.5 years (mean 6.5, median 6.9) with AHOM received no surgical treatment initially. In 23 (22.3%) FT was instilled initially, in 47 (45.6%) FT+, and in 33 (32.0%) NFT. The pathogen was established in 30%, 36%, and 42% of FT, FT+, and NFT patients, respectively, Staphylococcus aureus being the predominant isolate. Mean C reactive protein levels and erythrocyte sedimentation rates normalised in all treatment groups after two and four weeks, respectively. The mean duration of intravenous antimicrobial treatment in FT patients was 2.5 weeks, in FT+ patients 3.1 weeks, and in NFT patients 3.8 weeks (p < 0.05), whereas the mean duration of intravenous plus oral treatment was comparable (7.1 v 6.8 v 6.5 weeks).. The leucocyte penetrating fosfomycin performed similarly to extracellular beta lactams in the treatment of AHOM. Intravenous treatment for longer than 2.5 weeks offered no advantage.

Topics: Acute Disease; Adolescent; Anti-Bacterial Agents; Bacteremia; Bone and Bones; Child; Child, Preschool; Female; Fosfomycin; Humans; Infant; Lactams; Male; Osteomyelitis; Retrospective Studies; Staphylococcus

We present a case of meningitis that developed following a urinary tract infection caused by methicillin-resistant Staphylococcus aureus (MRSA) after transurethral resection of the prostate. The patient, a 69-year-old man with diabetes mellitis, underwent transurethral resection of the prostate following a diagnosis of benign prostatic hypertrophy. On the 4 th day after surgery, high fever occurred immediately after the removal of the indwelling urethral catheter. Cultures of urine and blood revealed MRSA. On the 6 th day after surgery, severe lumbago was evident and MRSA was isolated from cerebrospinal fluid. Separate administration of arbekacin or vancomycin, to which the isolated MRSA was sensitive, was not effective. Combined therapy with fosfomycin, vancomycin and human immunoglobulin effectively relieved the inflammation. Although it is generally reported that the pathogenicity of MRSA is low in the urinary tract, this case suggests that a urinary tract infection caused by MRSA can advance to sepsis and meningitis.

Topics: Aged; Bacteremia; Drug Therapy, Combination; Fosfomycin; Humans; Immunoglobulins; Male; Meningitis, Bacterial; Methicillin Resistance; Postoperative Complications; Prostatectomy; Staphylococcal Infections; Urinary Tract Infections; Vancomycin

We evaluated the protective effect of fosfomycin (FOM) and an enantiomer of fosfomycin [FOM (+); an isomer of FOM with no bactericidal activity] on murine gut-derived sepsis caused by Pseudomonas aeruginosa. Endogenous bacteremia was induced by administering cyclophosphamide (CY) and ampicillin to specific-pathogen-free mice fed P. aeruginosa. Treatment of mice with FOM at 250 mg/kg of body weight per day twice a day after the second CY administration significantly increased the survival rate compared to that for control mice treated with saline. Treatment with FOM (+) at 20 and 100 mg/kg also significantly increased the survival rate (from 30% for control mice to 80% for treated mice). The bacterial counts in the liver and blood were both significantly lower in FOM(+)-treated mice in comparison with those in liver and blood of saline-treated control mice. FOM(+) administration affected neither the bacterial colonization in the intestinal tract nor the leukocyte counts in the peripheral blood of the mice. After intravascular inoculation of P. aeruginosa, treatment of mice with FOM (+) did not enhance bacterial clearance from the blood of mice pretreated or not enhance bacterial clearance from the blood of mice pretreated or not pretreated with CY, FOM(+) significantly suppressed tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6 levels in the serum of mice after gut-derived sepsis. These results indicate that both FOM and FOM(+) have protective effects against P. aeruginosa bacteremia, despite a lack of specific activity of FOM(+), and suggest that FOM may possess immunomodulating activity and that it induces a protective effect. The protective mechanism is speculated to be that FOM modulates the vivo production of inflammatory cytokines.

Topics: Adjuvants, Immunologic; Animals; Anti-Bacterial Agents; Bacteremia; Colony Count, Microbial; Cyclophosphamide; Drug Interactions; Drug Resistance, Microbial; Fosfomycin; Interleukin-1; Interleukin-6; Intestines; Leukocyte Count; Liver; Macrophages, Peritoneal; Male; Mice; Pseudomonas aeruginosa; Pseudomonas Infections; Specific Pathogen-Free Organisms; Stereoisomerism; Tumor Necrosis Factor-alpha

The effects of 16 different beta-lactam-fosfomycin combinations against 50 bloodstream enterococci were compared by a disk diffusion technique. Cefotaxime exhibited the best interaction. By checkerboard studies, the cefotaxime-fosfomycin combination provided a synergistic bacteriostatic effect against 45 of the 50 isolates (MIC of cefotaxime at which 90% of the isolates were inhibited, >2,048 micrograms/ml; MIC of fosfomycin at which 90% of the isolates were inhibited, 128 micrograms/ml; mean of fractional inhibitory concentration indexes, 0.195). By killing curves, cefotaxime (at 64 micrograms/ml) combined with fosfomycin (at > or = 64 micrograms/ml) was bactericidal against 6 of 10 strains tested.

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactams; Drug Therapy, Combination; Enterococcus; Fosfomycin; Microbial Sensitivity Tests

Multi-drug resistant strains of Salmonella isolated from blood and bone marrow cultures of pyrexial patients received from physicians, hospitals and different clinics were studied from May to November, 1993. Of 2143 samples collected, 424(20%) cases yielded the growth of different organisms. Out of these 266(63%) were positive for Salmonella strains. The strains isolated were Salmonella typhi 239(90%) and Salmonella paratyphi A 27(10%). Two hundred twenty (82%) strains of Salmonella showed increased beta-lactamase activity and an alarming increase in resistance against commonly used antibiotics for enteric fever.

Topics: 4-Quinolones; Anti-Infective Agents; Bacteremia; beta-Lactamases; Bone Marrow; Cephalosporin Resistance; Chloramphenicol Resistance; Drug Resistance, Microbial; Drug Resistance, Multiple; Fosfomycin; Humans; Penicillin Resistance; Salmonella paratyphi A; Salmonella typhi; Trimethoprim Resistance; Trimethoprim, Sulfamethoxazole Drug Combination; Typhoid Fever