fosfomycin and Gram-Positive-Bacterial-Infections

Daptomycin is a bactericidal lipopeptide antibiotic approved for the treatment of systemic infections (i.e. skin and soft tissue infections, bloodstream infections, infective endocarditis) caused by Gram-positive cocci. It is often prescribed in association with a partner drug to increase its bactericidal effect and to prevent the emergence of resistant strains during treatment; however, its synergistic properties are still under evaluation.. We performed a systematic review to offer clinicians an updated overview of daptomycin synergistic properties from in vitro and in vivo studies. Moreover, we reported all in vitro and in vivo data evaluating daptomycin in combination with other antibiotic agents, subdivided by antibiotic classes, and a summary graph presenting the most favourable combinations at a glance.. A total of 92 studies and 1087 isolates (723 Staphylococcus aureus, 68 Staphylococcus epidermidis, 179 Enterococcus faecium, 105 Enterococcus faecalis, 12 Enterococcus durans) were included. Synergism accounted for 30.9% of total interactions, while indifferent effect was the most frequently observed interaction (41.9%). Antagonistic effect accounted for 0.7% of total interactions. The highest synergistic rates against S. aureus were observed with daptomycin in combination with fosfomycin (55.6%). For S. epidermidis and Enterococcus spp., the most effective combinations were daptomycin plus ceftobiprole (50%) and daptomycin plus fosfomycin (63.6%) or rifampicin (62.8%), respectively.. We believe this systematic review could be useful for the future updates of guidelines on systemic infections where daptomycin plays a key role.

Topics: Anti-Bacterial Agents; Daptomycin; Drug Synergism; Fosfomycin; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Staphylococcus aureus

There are challenges regarding increased global rates of microbial resistance and the emergence of new mechanisms that result in microorganisms becoming resistant to antimicrobial drugs. Fosfomycin is a broad-spectrum bactericidal antibiotic effective against Gram-negative and certain Gram-positive bacteria, such as Staphylococci, that interfere with cell wall synthesis. During the last 40 years, fosfomycin has been evaluated in a wide range of applications and fields. Although numerous studies have been done in this area, there remains limited information regarding the prevalence of resistance. Therefore, in this review, we focus on the available data concerning the mechanisms and increasing resistance regarding fosfomycin.

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Fosfomycin; Geography; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Prevalence

Due to the increase in antimicrobial resistance, strategies such as antimicrobial stewardship programs (ASP) have been developed to improve the clinical results, decrease the adverse effects and the development of resistances and ensure cost-effective therapies. Fosfomycin has a unique mechanism of action against Gram-positive and Gram-negative bacteria. Cross-resistance is uncommon; however, fosfomycin should be used in combination in severe infections to avoid selecting resistant mutations. Fosfomycin's oral formulation facilitates sequential treatment, has low toxicity and high tissue penetration, even in the central nervous system and bone. Fosfomycin is active against resistant Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin- resistant enterococci and penicillin-resistant Streptococcus pneumoniae, as well as against resistant Gram-negative bacteria such as extended-spectrum beta-lactamase-producing and carbapenemase-producing enterobacteria. Fosfomycin is therefore useful for cases of persistent bacteremia, skin and soft tissue infections, as a glycopeptide-sparing and carbapenem-sparing drug for healthcare-associated infections and for polymicrobial infections. Published studies have demonstrated the synergy between fosfomycin and beta-lactams, daptomycin and glycopeptides against MSSA and MRSA; with linezolid in biofilm-associated infections and with aminoglycosides and colistin against Gram-negative bacteria, providing a nephroprotective effect.

Topics: Animals; Anti-Bacterial Agents; Antimicrobial Stewardship; Bacterial Infections; Drug Resistance, Multiple, Bacterial; Fosfomycin; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans

Antimicrobial resistance is a major and emerging threat worldwide. New antimicrobials have been unable to meet the resistance challenge, and treatment options are limited for a growing number of resistant pathogens. More and more clinicians are relying on older antimicrobials for the treatment of multidrug-resistant (MDR) bacteria. Some older antimicrobials have maintained excellent in vitro activity against highly resistant pathogens. In some instances, use of older agents is limited by unfavourable pharmacokinetic/pharmacodynamic characteristics and/or toxicities. In general, clinical data pertaining to the use of older agents for the treatment of MDR pathogens are scarce. Research efforts should be focused on the evaluation of older agents for the treatment of MDR pathogens as well as evaluating how these agents perform in complex patient populations with various and multiple co-morbid conditions.

Topics: Aminoglycosides; Anti-Bacterial Agents; Drug Combinations; Drug Resistance, Multiple, Bacterial; Fosfomycin; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Polymyxins; Sulfamethizole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

The aim of this review was to evaluate the susceptibility of contemporary Gram-positive and Gram-negative bacteria to fosfomycin. PubMed and Scopus databases were systematically searched to identify studies published in print or electronically from January 2010 until June 2015. In total, 84 studies were selected. Susceptibility to fosfomycin of Staphylococcus aureus ranged between 33.2% and 100% (frequency=91.7%, 95% confidence interval 88.7-94.9%), of Enterococcus spp. from 30% to 100% (Enterococcus faecium 92.6%, 85.2-100%; Enterococcus faecalis 96.8%, 92.5-100%), of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli from 81% to 100% (95.1%, 94.3-95.9%), of ESBL-producing Klebsiella pneumoniae from 15% to 100% (83.8%, 78.7-89.4%) and of carbapenem-resistant (CR) K. pneumoniae from 39.2% to 100% (73.5%, 66.4-81.4%). Staphylococcus aureus (including meticillin-resistant strains) and E. coli (including ESBL-producing strains) were the most likely to be susceptible with low minimum inhibitory concentrations (MICs). Enterococci (particularly vancomycin-resistant E. faecium) and K. pneumoniae (especially CR strains) were less susceptible with higher MIC50 and MIC90 values. Two studies reported decreasing susceptibility of ESBL-producing E. coli to fosfomycin. In conclusion, guided by local susceptibility data, fosfomycin could be considered for the treatment of patients with infections due to problematic multidrug-resistant bacteria.

Topics: Anti-Bacterial Agents; Fosfomycin; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests

Fosfomycin, originally named phosphonomycin, was discovered in Spain in 1969. There are three forms of fosfomycin: fosfomycin tromethamine (a soluble salt) and fosfomycin calcium for oral use, and fosfomycin disodium for intravenous use. Fosfomycin is a bactericidal antibiotic that interferes with cell wall synthesis in both Gram-positive and Gram-negative bacteria by inhibiting the initial step involving phosphoenolpyruvate synthetase. It has a broad spectrum of activity against a wide range of Gram-positive and Gram-negative bacteria. It is highly active against Gram-positive pathogens such as Staphylococcus aureus and Enterococcus, and against Gram-negative bacteria such as Pseudomonas aeruginosa and Klebsiella pneumoniae. Its unique mechanism of action may provide a synergistic effect to other classes of antibiotics including beta-lactams, aminoglycosides, and fluoroquinolones. Oral fosfomycin is mainly used in the treatment of urinary tract infections, particularly those caused by Escherichia coli and Enterococcus faecalis. Intravenous fosfomycin has been administered in combination with other antibiotics for the treatment of nosocomial infections due to multidrug-resistant (MDR) Gram-positive and Gram-negative bacteria. Fosfomycin has good distribution into tissues, achieving clinically relevant concentrations in serum, kidneys, bladder wall, prostate, lungs, inflamed tissues, bone, cerebrospinal fluid, abscess fluid, and heart valves. Fosfomycin is well tolerated, with a low incidence of adverse events. Further randomized controlled trials are needed in order to evaluate the efficacy of intravenous fosfomycin for the management of nosocomial infections due to MDR pathogens.

Topics: Anti-Bacterial Agents; Cross Infection; Enterococcus faecalis; Escherichia coli; Fosfomycin; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Klebsiella pneumoniae; Pseudomonas aeruginosa; Urinary Tract Infections

The continuously increasing problem of multidrug-resistant (extended-spectrum beta-lactamase and/or metallo-beta-lactamase producing) bacteria in recent years has created the need to re-evaluate antibiotic therapy for these infections. Fosfomycin is reconsidered to be an alternative treatment agent for such infections. Fosfomycin was first discovered in Spain in 1969 from cultures of Streptomyces species and originally called phosphonomycin. In the early years, fosfomycin was administered parenterally to the patients with many serious infections including meningitis. In some European countries, fosfomycin is occasionally administered for the initial empirical therapy of sepsis or soft-tissue infections. Although in most European countries fosfomycin has been used for many years, it has become available in clinical use only recently in Turkey. In USA, the Food and Drug Administration (FDA) has approved fosfomycin only for the treatment of patients with uncomplicated cystitis. The use of fosfomycin in the treatment of multidrug-resistant bacterial infections and in the treatment of pediatric cancer patients with fever and neutropenia in combination with other antibiotics, has withdrawn attention to this agent. Fosfomycin has a rapid bactericidal effect and a wide antibacterial spectrum, including methicillin-resistant Staphylococcus aureus, glycopeptide-susceptible or resistant enterococci and a large number of gram-negative pathogens. Since it has a long serum half-life and high concentrations are achieved in urine after oral administration; fosfomycin deserved further consideration for single-dose treatment of urinary tract infections caused by Escherichia coil and Enterococcus faecalis. In this review article the properties, mechanisms of action and resistance, antibacterial spectrum, clinical use, toxicity and adverse reactions of fosfomycin have been summarized.

Topics: Anti-Bacterial Agents; Enterococcus faecalis; Escherichia coli Infections; Fosfomycin; Gram-Positive Bacterial Infections; History, 20th Century; History, 21st Century; Humans; Urinary Tract Infections

The advancing antimicrobial drug resistance in Gram-positive cocci complicates the selection of appropriate therapy. The re-evaluation of older antibiotics may prove useful in expanding relevant therapeutic options.. We sought to evaluate fosfomycin for the treatment of infections caused by methicillin-resistant staphylococci, vancomycin-resistant enterococci, and penicillin-non-susceptible pneumococci.. We searched in PubMed, Scopus, and the Cochrane Library for studies evaluating the antimicrobial activity of fosfomycin against the above-mentioned pathogens, or the in vivo or clinical effectiveness of fosfomycin for the treatment of infections caused by these pathogens.. As reported in the identified studies, the susceptibility rate of methicillin-resistant Staphylococcus aureus to fosfomycin was > or = 90% in 12/22, and 50-90% in 7/22 studies; the cumulative susceptibility rate was 87.9% (4240/4892 isolates). The cumulative susceptibility rate of vancomycin-resistant enterococci to fosfomycin was 30.3% (183/604 isolates), and that of penicillin-non-susceptible pneumococci was 87.2% (191/219 isolates). Clinical data show that fosfomycin, primarily in combination regimens, has been associated with clinical success in 28/29 (96.6%) cases of infection (mainly pneumonia, bacteremia, and meningitis) by fosfomycin-susceptible isolates of methicillin-resistant S. aureus. The above data support further research on the role of fosfomycin against infections caused by Gram-positive cocci with advanced antimicrobial drug resistance.

Topics: Animals; Clinical Trials as Topic; Drug Evaluation, Preclinical; Drug Resistance, Bacterial; Enterococcus; Fosfomycin; Gram-Positive Bacterial Infections; Gram-Positive Cocci; Humans; Methicillin-Resistant Staphylococcus aureus; Streptococcus pneumoniae; Treatment Outcome

Lower urinary tract infection remains frequent particularly in women, despite improvement in therapeutic means. It seems likely to revisit bacterial epidemiology and therapeutic available strategies. To analyze elements in presence i.e. infecting bacteria and antibiotics still active or identification of acquired resistance mechanisms should permit to establish the evolution during the last 10 years. The study shows that bacterial epidemiology in urinary tract infection has not changed significantly, despite antibiotic selective pressure expected from overused antibiotics. However few enterobacteriaceae more resistant than Escherichia coli have emerged, but the latter remains predominant. Development of resistance has concerned Negram, amoxicillin and Augmentin, but several active molecules such as ciprofloxacin, Monuril remain available. Duration of treatments are still discussed but there is a tend toward short durations and even mono-doses. The control of lower urinary tract infections remains relatively easy provided that a good therapeutic choice is based on well documented bacteriologic data (infecting species susceptible to the available antibiotics).

Topics: Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Anti-Infective Agents; Ciprofloxacin; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Fosfomycin; Gram-Positive Bacterial Infections; Humans; Male; Microbial Sensitivity Tests; Proteus Infections; Proteus mirabilis; Time Factors; Urinary Tract Infections

The shortage of new antimicrobial agents has made the scientific community reconsider the potential value of old antibiotics. A search of the literature was performed to compile relevant evidence regarding the effectiveness and safety of fosfomycin for the treatment of patients with gram-positive and/or gram-negative bacterial infections (excluding urinary tract infection and gastrointestinal infection). Of 1311 potentially relevant studies, 62 studies were reviewed in detail. Of 1604 patients with various gram-positive and gram-negative infections of various body sites (including pneumonia and other respiratory infections; osteomyelitis; meningitis; ear, nose, and throat infections; surgical infections; obstetric and gynecological infections; arthritis; septicemia; peritonitis; cervical lymphadenitis; eye infections; diabetic foot infections; and typhoid fever) being treated with fosfomycin alone or in combination with other antibiotics, cure was achieved in 1302 (81.1%) of the patients, and improvement was noted in 47 (2.9%). In comparative perioperative prophylaxis trials that included a total of 1212 patients (mainly patients undergoing colorectal surgery), the fosfomycin-metronidazole combination led to results that were similar to those achieved with the combination of other antibiotics (doxycycline, ampicillin, or cephalothin) and metronidazole. In an era in which there is a shortage of new antibiotics, fosfomycin might be considered to be an alternative treatment agent for infections caused by gram-positive and gram-negative bacteria, in addition to its traditional use in treating uncomplicated urinary tract and gastrointestinal infections. Further research on the in vitro antimicrobial activity of fosfomycin, especially against multidrug-resistant pathogens (such as extended-spectrum beta-lactamase-producing and/or metallo-beta-lactamase-producing enterobacteriaceae and Pseudomonas aeruginosa, and on the effectiveness and safety of the drug in the treatment of patients with such infections may be warranted.

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Drug Therapy, Combination; Fosfomycin; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans

Fosfomycin is an natural antibiotic with an epoxide structure and low molecular weight which acts in the first stage of peptidoglycan synthesis of the bacterial wall. It has a rapid bactericide effect, and a wide spectrum, including methicillin-resistant Staphylococcus aureus and intermediate glycopeptide-susceptible or -resistant enterococci. Over the years it has maintained its activity and has shown stable rates of resistance. It has synergistic action, which is additive or indifferent with glycopeptides, linezolid, quinupristin-dalfopristin, betalactams, aminoglycosides, ansamycines, nitroimidazoles and quinolones, without antagonism. It can be administered orally or parenterally in a wide range of doses, it does not bind to plasma proteins, and has a good distribution volume, reaching high concentrations in the interstitial fluid and tissues. It is eliminated in the kidneys in its active form without metabolites and is dialyzable. It has been used in a number of indications, including urinary, respiratory, intraabdominal, obstetric-gynecologic, central nervous system and osteoarticular infections, with satisfactory overall results in 80% of cases and minimal side effects. It does not cause important changes in the normal human flora. As additional effects it has the capacity to favor phagocytosis, act as an immunomodulator and protect human cells from cisplatin, cyclosporin, aminoglycoside, vancomycin, amphotericin B and polymixin toxicity. Oral fosfomycin is currently clearly indicated in urinary infections and gastroenteritis, and parenteral fosfomycin in high doses and in combination with other drugs in severe inhospital infections caused by problematic pathogens, including multiresistant staphylococci and enterococci, and in immunodepressed patients treated with nephrotoxic drugs.

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Drug Synergism; Drug Therapy, Combination; Fosfomycin; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans

Fosfomycin tromethamine is a phosphonic acid bactericidal agent with in vitro activity against most urinary tract pathogens. It is particularly active against Escherichia coli, and Citrobacter, Enterobacter, Klebsiella, Serratia and Enterococcus spp. There appears to be little cross-resistance between fosfomycin and other antibacterial agents, possibly because it differs from other agents in its general chemical structure and site of action. In its new formulation as the oral tromethamine salt, fosfomycin has 34 to 41% oral bioavailability, has a mean elimination half-life of 5.7 hours, and is primarily excreted unchanged in the urine. Following a single 3 g oral dose, peak urinary concentrations occur within 4 hours and remain high (> 128 mg/L) for 24 to 48 hours, which is sufficient to inhibit most urinary tract pathogens. In clinical trials in patients with acute uncomplicated lower urinary tract infection, single-dose fosfomycin tromethamine therapy was effective, and comparable with several other antibacterial agents given either as single-dose or multiple-dose treatments [e.g. beta-lactam and fluoroquinolone agents, cotrimoxazole (trimethoprim-sulfamethoxazole), nitrofurantoin and pipemidic acid]. Bacteriological eradication rates of 75 to 90% were achieved 5 to 11 days after therapy, with eradication rates of 62 to 93% 4 to 6 weeks after therapy. In 3 large double-blind comparisons with ciprofloxacin, cotrimoxazole and nitrofurantoin, 99% of fosfomycin tromethamine recipients and 100% of patients receiving comparator agents were considered clinically cured or improved after therapy. Fosfomycin tromethamine is well tolerated, with a low incidence of adverse events. These comprise mainly gastrointestinal symptoms that are transient, mild and self-limiting. Thus, fosfomycin tromethamine achieves high clinical and bacteriological cure rates in patients with acute uncomplicated lower urinary tract infection and is well tolerated. The single-dose administration regimen and favourable US pregnancy category rating of fosfomycin tromethamine should also encourage its use in this indication.

Topics: Acute Disease; Administration, Oral; Drug Administration Schedule; Female; Fosfomycin; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Pregnancy; Randomized Controlled Trials as Topic; Tromethamine; Urinary Tract Infections

Topics: Aerococcus; Anti-Bacterial Agents; Fosfomycin; Gram-Positive Bacterial Infections; Humans; Urinary Tract Infections

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

Fosfomycin has re-emerged as a possible therapeutic alternative for the treatment of resistant bacterial pathogens. Its main mechanism of action is the inhibition of the initial step of cell wall synthesis and is active against both Gram-positive and Gram-negative bacteria. However, its clinical effectiveness against multidrug resistant bacteria remains largely unknown. Therefore, we aim to evaluate the clinical and microbiological effectiveness of intravenous fosfomycin as well as its safety in a tertiary care teaching hospital in Lebanon.. This is a retrospective chart review of adult patients who had presented to the hospital and were treated with intravenous fosfomycin for at least 24 hours for any type of infection between 2014 and 2019.. Among 31 episodes treated with intravenous fosfomycin, 68% had an overall favorable clinical response. In 84% of the episodes, fosfomycin was administered in combination with other antibiotics, commonly tigecycline. Of those with available cultures at end of therapy, 73% achieved microbiological success. No relapse was documented within 30 days of completion of therapy. In the episodes secondary to resistant pathogens, the rates of favorable clinical outcome and microbiological success at the end of therapy were 71% and 73%, respectively. Fosfomycin resistance developed in two cases and mild adverse events occurred in 65% of the episodes during the course of treatment.. Fosfomycin is a safe and effective option in the treatment of multi-drug resistant infections. Nevertheless, careful stewardship is important to maintain its efficacy and to reduce the risk of selection of antimicrobial resistance.

Topics: Administration, Intravenous; Adolescent; Adult; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Female; Fosfomycin; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Lebanon; Male; Middle Aged; Retrospective Studies; Tertiary Care Centers; Young Adult

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

Enterococcus faecalis and Enterococcus faecium can cause community-acquired and nosocomial infections. Combination antibiotic therapies have a distinct advantage over monotherapies in terms of their synergistic effect. In the study, it was aimed to investigate in vitro activity of vancomycin combined with fosfomycin by agar dilution method against VRE strains.. A total of 30 clinical VRE strains were included in the study. Bacterial identifications of the strains were undertaken using conventional routine methods. The resistance to vancomycin was investigated using the broth microdilution method compared to fosfomycin by agar dilution method, and the results were interpreted in accordance with the CLSI guidelines. All experiments contained 25 mg/mL glucose-6-phosphate for fosfomycin. The fractional inhibitory concentration (FIC) indexes (FICI) were interpreted as synergism, FICI ≤ 0.5. Additionally, two strains in 30 VRE were studied to determine the time-kill curves to verify the synergistic results. Both antibiotics were studied at 1 x MIC in the tests. Viable counts were determined at 0, 4, 8, 12, and 24-hour intervals. Time-kill curves were constructed by plotting mean colony forming unit counts versus time.. Susceptibility rate to fosfomycin was found at 16.6% (5/30). The MIC50,90 and MICrange values of antimi-crobials were 512, 512, and 512 - 1,024 mg/L for vancomycin, and 128, 128, and 64 - 160 mg/L for fosfomycin. The rate of synergism was found as 100%.. The result shows that the combination of vancomycin with fosfomycin gives hope that it may be an option in the treatment of infections caused by VRE.

Topics: Agar; Anti-Bacterial Agents; Enterococcus faecium; Fosfomycin; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Vancomycin

The aim of this study was to investigate the mechanisms of fosfomycin resistance and epidemiological characteristics in fosfomycin-resistant enterococci in China.. A collection of 761 enterococcal clinical isolates from a teaching hospital in Wenzhou, China were studied. The fosfomycin susceptibility of the isolates was investigated by the agar dilution method. The isolates were also analysed for mechanisms of re fosfomycin resistance by PCR and quantitative real-time PCR. Furthermore, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) were performed to analyse the molecular epidemiological characteristics of the fosfomycin-resistant isolates.. In this study, 0.3% (1/372) of Enterococcus faecalis and 4.9% (19/389) of Enterococcus faecium clinical isolates were found to be resistant to fosfomycin. Among the 20 fosfomycin-resistant isolates, 5 harboured the fosB gene, 10 carried multiple amino acid substitutions in MurA, and 6 showed high-level expression of the fosX gene; of note, 1 isolate simultaneously carried fosB and amino acid mutation in MurA. Furthermore, a high degree of homology in the fosfomycin-resistant enterococci was confirmed using MLST and PFGE.. These finding demonstrate that the fosB gene, mutations in the fosfomycin target enzyme MurA, and a high expression level of fosX were the resistance mechanisms in these fosfomycin-resistant enterococci.

Topics: Bacterial Proteins; China; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Enterococcus faecalis; Enterococcus faecium; Fosfomycin; Gram-Positive Bacterial Infections; Hospitals, Teaching; Humans; Microbial Sensitivity Tests; Molecular Epidemiology; Multilocus Sequence Typing; Mutation; Phylogeny

Oral fosfomycin may constitute an alternative for the treatment of lower urinary tract infections (UTIs) in kidney transplant recipients (KTRs), particularly in view of recent safety concerns with fluroquinolones. Specific data on the efficacy and safety of fosfomycin in KTR are scarce. We performed a retrospective study in 14 Spanish hospitals including KTRs treated with oral fosfomycin (calcium and trometamol salts) for posttransplant cystitis between January 2005 and December 2017. A total of 133 KTRs developed 143 episodes of cystitis. Most episodes (131 [91.6%]) were produced by gram-negative bacilli (GNB), and 78 (54.5%) were categorized as multidrug resistant (including extended-spectrum β-lactamase-producing Enterobacteriaceae [14%] or carbapenem-resistant GNB [3.5%]). A median daily dose of 1.5 g of fosfomycin (interquartile range [IQR]: 1.5-2) was administered for a median of 7 days (IQR: 3-10). Clinical cure (remission of UTI-attributable symptoms at the end of therapy) was achieved in 83.9% (120/143) episodes. Among those episodes with follow-up urine culture, microbiological cure at month 1 was achieved in 70.2% (59/84) episodes. Percutaneous nephrostomy was associated with a lower probability of clinical cure (adjusted odds ratio: 10.50; 95% confidence interval: 0.98-112.29; P = 0.052). In conclusion, fosfomycin is an effective orally available alternative for treating cystitis among KTRs.

Topics: Administration, Oral; Adult; Aged; Anti-Bacterial Agents; Female; Follow-Up Studies; Fosfomycin; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Kidney Transplantation; Logistic Models; Male; Middle Aged; Postoperative Complications; Retrospective Studies; Spain; Treatment Outcome; Urinary Tract Infections

Over recent years we have witnessed an increase in the resistance of microorganisms to the available antimicrobials and a decrease in the number of new antimicrobials. Fosfomycin is a safe and cheap broad-spectrum antibiotic which has shown very promising results in combination therapy, mainly against gram-negative microorganisms. Little is known, however, about its clinical efficacy against gram-positive microorganisms.. We performed a retrospective review of all patients with severe gram-positive infections who received fosfomycin as part of their treatment from 2011 to 2017. We also performed in vitro time-kill assays to study the behaviour of fosfomycin with different antimicrobials against two strains of methicillin-resistant Staphylococcus aureus (MRSA) and two strains of methicillin-susceptible S. aureus (MSSA).. Seventy-five patients were treated with different fosfomycin combinations. Among them, 61 (81%) were successfully treated. Daptomycin plus fosfomycin was the most effective combination. Overall, the treatment with fosfomycin was safe, and side effects were minor. There was only one major side effect that resolved after discontinuation of therapy. Time-kill studies demonstrated increased activity of fosfomycin combinations, with daptomycin-fosfomycin being the most active combination against both MRSA and MSSA strains.. Our results suggest that antimicrobial combinations including fosfomycin are an alternative and effective approach for gram-positive infections.

Topics: Anti-Bacterial Agents; Dose-Response Relationship, Drug; Drug Combinations; Fosfomycin; Gram-Positive Bacterial Infections; Gram-Positive Cocci; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Treatment Outcome

This study aimed to explore daptomycin combined with fosfomycin or rifampin against the planktonic and adherent linezolid-resistant isolates of Enterococcus faecalis.. Four linezolid-resistant and four linezolid-sensitive isolates of E. faecalis which formed biofilms were collected for this study. Biofilm biomasses were detected by crystal violet staining and the adherent cells in the mature biofilms were quantified by c.f.u. determination.. Daptomycin alone, or combined with fosfomycin or rifampin (4×MIC) demonstrated bactericidal activities on the planktonic cells, and daptomycin combined with fosfomycin killed more planktonic cells (at least 1-log10 c.f.u. ml. Daptomycin combined with fosfomycin demonstrated better effect on the planktonic and adherent linezolid-resistant isolates of E. faecalis than daptomycin or fosfomycin alone. The role of rifampin in the treatment of E. faecalis isolates is discrepant and needs more studies.

Topics: Anti-Bacterial Agents; Bacterial Adhesion; Biofilms; Cell Line; Daptomycin; Drug Resistance, Bacterial; Enterococcus faecalis; Fosfomycin; Gram-Positive Bacterial Infections; Humans; Linezolid; Microbial Sensitivity Tests; Plankton; Rifampin

For treatment of peritoneal dialysis-related peritonitis, intraperitoneal administration of antibiotics remains the preferable route. For home-based therapy, patients are commonly supplied with peritoneal dialysis fluids already containing antimicrobial agents. The present study set out to investigate the compatibility of fosfomycin with different peritoneal dialysis fluids, namely, Extraneal

Topics: Anti-Bacterial Agents; Dialysis Solutions; Disk Diffusion Antimicrobial Tests; Drug Interactions; Fosfomycin; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Peritoneal Dialysis; Peritonitis

Physicians are facing a worldwide increase in multidrug-resistant (MDR) organisms. Eradication of such bacteria, including so called superbugs (XDR), may cause physicians to prescribe last-resort antibiotics. However, experience with these drugs is limited and few data are available.. A before and after retrospective study was conducted from January 2008 to June 2016. Prescriptions of parenteral antimicrobials considered as last-resort antibiotics (colistin, fosfomycin, tigecycline and temocillin) were reviewed by 4 infectious disease specialists (according to microbiology results, susceptibility testing, clinical situation and alternative agents), while doses were analysed by a pharmacist. As a second step, the cohort was split before and after 2013 coinciding with the arrival of a referent in antimicrobial stewardship.. The treatment of 77 patients with a mean age of 55.4 ± 18.7 years was analysed. The majority were treated for gram-negative rods (69.2%), especially Pseudomonas and Klebsiella spp. and Escherichia coli while 20.0% of patients were treated for gram-positive cocci (mainly Staphylococcus aureus) and the remainder were polymicrobial. Of 84 prescriptions, fosfomycin was the most frequently prescribed (47.6%), followed by colistin (40.5%), tigecycline (10.7%) and temocillin (1.2%). Outcomes were favorable in 75.3% of patients. In patients with MDR and XDR infections (n = 54), the mortality rate was 11.1%. After 2013, there were significantly fewer prescriptions of last-resort antibiotics for susceptible microorganisms (29.2% vs 6.9%), in the absence of supporting microbiology results (22.9% vs 3.5%) and fewer dose errors (56.2% vs 27.6%) (P = 0.02).. Reinforcement of the antimicrobial stewardship task force seems to be valuable for promoting the better use of last-resort antibiotics.

Topics: Adult; Advisory Committees; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antimicrobial Stewardship; Colistin; Female; Fosfomycin; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Male; Middle Aged; Retrospective Studies; Treatment Outcome

Of 890 vancomycin-resistant Enterococcus faecium isolates obtained by rectal screening from patients in Pittsburgh, Pennsylvania, USA, 4 had MICs >1,024 μg/mL for fosfomycin. These isolates had a Cys119Asp substitution in the active site of UDP-N-acetylglucosamine enolpyruvyl transferase. This substitution increased the fosfomycin MIC >4-fold and rendered this drug inactive in biochemical assays.

Topics: Alkyl and Aryl Transferases; Amino Acid Substitution; Anti-Bacterial Agents; Bacterial Proteins; Drug Resistance, Bacterial; Enterococcus faecium; Fosfomycin; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Mutation; Pennsylvania; Vancomycin

This study describes the population pharmacokinetics of fosfomycin in critically ill patients. In this observational study, serial blood samples were taken over several dosing intervals of intravenous fosfomycin treatment. Blood samples were analyzed using a validated liquid chromatography-tandem mass spectrometry technique. A population pharmacokinetic analysis was performed using nonlinear mixed-effects modeling. Five hundred fifteen blood samples were collected over one to six dosing intervals from 12 patients. The mean (standard deviation) age was 62 (17) years, 67% of patients were male, and creatinine clearance (CLCR) ranged from 30 to 300 ml/min. A two-compartment model with between-subject variability on clearance and volume of distribution of the central compartment (Vc) described the data adequately. Calculated CLCR was supported as a covariate on fosfomycin clearance. The mean parameter estimates for clearance on the first day were 2.06 liters/h, Vc of 27.2 liters, intercompartmental clearance of 19.8 liters/h, and volume of the peripheral compartment of 22.3 liters. We found significant pharmacokinetic variability for fosfomycin in this heterogeneous patient sample, which may be explained somewhat by the observed variations in renal function.

Topics: Aged; Anti-Bacterial Agents; APACHE; Biological Availability; Critical Illness; Drug Administration Schedule; Female; Fosfomycin; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Greece; Humans; Intensive Care Units; Male; Middle Aged; Models, Statistical; Multiple Organ Failure; Opportunistic Infections

Enterococcal implant-associated infections are difficult to treat because antibiotics generally lack activity against enterococcal biofilms. We investigated fosfomycin, rifampin, and their combinations against planktonic and adherent Enterococcus faecalis (ATCC 19433) in vitro and in a foreign-body infection model. The MIC/MBClog values were 32/>512 μg/ml for fosfomycin, 4/>64 μg/ml for rifampin, 1/2 μg/ml for ampicillin, 2/>256 μg/ml for linezolid, 16/32 μg/ml for gentamicin, 1/>64 μg/ml for vancomycin, and 1/5 μg/ml for daptomycin. In time-kill studies, fosfomycin was bactericidal at 8× and 16× MIC, but regrowth of resistant strains occurred after 24 h. With the exception of gentamicin, no complete inhibition of growth-related heat production was observed with other antimicrobials on early (3 h) or mature (24 h) biofilms. In the animal model, fosfomycin alone or in combination with daptomycin reduced planktonic counts by ≈4 log10 CFU/ml below the levels before treatment. Fosfomycin cleared planktonic bacteria from 74% of cage fluids (i.e., no growth in aspirated fluid) and eradicated biofilm bacteria from 43% of cages (i.e., no growth from removed cages). In combination with gentamicin, fosfomycin cleared 77% and cured 58% of cages; in combination with vancomycin, fosfomycin cleared 33% and cured 18% of cages; in combination with daptomycin, fosfomycin cleared 75% and cured 17% of cages. Rifampin showed no activity on planktonic or adherent E. faecalis, whereas in combination with daptomycin it cured 17% and with fosfomycin it cured 25% of cages. Emergence of fosfomycin resistance was not observed in vivo. In conclusion, fosfomycin showed activity against planktonic and adherent E. faecalis. Its role against enterococcal biofilms should be further investigated, especially in combination with rifampin and/or daptomycin treatment.

Topics: Acetamides; Ampicillin; Animals; Anti-Bacterial Agents; Bacterial Adhesion; Biofilms; Calorimetry; Daptomycin; Disease Models, Animal; Drug Therapy, Combination; Enterococcus faecalis; Foreign Bodies; Fosfomycin; Gentamicins; Gram-Positive Bacterial Infections; Guinea Pigs; Linezolid; Male; Microbial Sensitivity Tests; Oxazolidinones; Rifampin; Vancomycin

The presence and characterisation of plasmid-mediated fosfomycin resistance determinants were investigated among 45 clinical vancomycin-resistant enterococci (VRE) isolated in Zhejiang Province, China. In total, 19 VRE were resistant to fosfomycin, of which 18 isolates had conjugative fosfomycin resistance and were positive for fosB. No reported fos genes were detected in the remaining isolate. Among the 18 fosB-carrying isolates, the fosB gene was always flanked by tnpA, suggesting the same novel fosB transposon. In 10 of the 18 fosB-carrying isolates, the fosB and tnpA genes were found reversely inserted in the vanA transposon Tn1546. In the remaining eight isolates the fosB and vanA genes were located on different plasmids. These findings indicate that acquisition of the conjugative plasmid harbouring the novel fosB transposon (ISL3-like transposon) and the Tn1546-like transposon (containing vanA and fosB) may explain, at least in part, the recent increase in fosfomycin-resistant Enterococcus faecium in China.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Carbon-Oxygen Ligases; Conjugation, Genetic; DNA Transposable Elements; Drug Resistance, Bacterial; Enterococcus; Fosfomycin; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Multilocus Sequence Typing; Plasmids; Proto-Oncogene Proteins c-fos; Transposases; Vancomycin; Vancomycin Resistance

In order to investigate the prevalence of fosfomycin-resistance (fos) determinants in Enterococcus faecium, clinical strains were collected from hospitals throughout China between January 2008 and December 2009. Antimicrobial susceptibility testing was performed, after which the fos genes in all isolates and van genes in vancomycin-resistant isolates were characterized by PCR and sequencing. Conjugation experiments were carried out with fosB-positive E. faecium, DNA fragments flanking the fosB3 gene were sequenced and the genetic environment of fosB3 was analysed. Fosfomycin-resistant E. faecium (FREF) strains were characterized further by multilocus sequence typing (MLST) and PFGE. Among 145 E. faecium clinical isolates, 10 were resistant to fosfomycin with MICs>1024 mg l(-1) including six vancomycin-resistant strains of which five were vanA-positive and the sixth vanM-positive. All ten FREF strains harboured the fosB3 gene. Fosfomycin resistance and fosB3 could be transferred by conjugation from nine isolates. The fosB3 and tnpA genes were located in a circular DNA intermediate in all FREF strains and reversely inserted into vanA transposon Tn1546 in four vanA-positive FREF isolates. Ten different PFGE types and seven MLST types were found among the ten fosB3-positive isolates, while all strains belonged to the common clonal complex CC17. In conclusion, the transferable fosfomycin-resistance determinant fosB3 plays an important role in E. faecium resistance to fosfomycin in China.

Topics: Bacterial Proteins; China; Drug Resistance, Bacterial; Enterococcus faecium; Fosfomycin; Gram-Positive Bacterial Infections; Humans; Vancomycin

To determine the in vitro activity of Fosfomycin tromethamine against extended spectrum beta-lactamase producing uropathogens.. Experimental study.. Department of Microbiology, Armed Forces Institute of Pathology, Rawalpindi, from October 2011 to October 2012.. A total of 381 culture positive ESBL producing isolates from 2400 urine samples submitted over a period of one year were included in this study. Identification of isolates was done by standard biochemical profile of the organisms. The antimicrobial susceptibility of culture positive isolates was performed by disk diffusion method as recommended by Clinical Laboratory Standard Institute guidelines (CLSI).. The antimicrobial activity of Fosfomycin to various isolates revealed that 93% of E. coli, 64% Klebsiella spp. 50% Proteus spp. 75% Enterobacter cloacae, 100% Citrobacter freundii, 100% Burkholderia spp. 100% Serratia spp. and 50% Stenotrophomonas maltophilia were susceptible to this chemical compound.. Fosfomycin showed excellent effectiveness to most of the common ESBL producing bacteria such as E. coli, Klebsiella and Proteus spp.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamases; Child; Child, Preschool; Drug Resistance, Bacterial; Escherichia coli Infections; Female; Fosfomycin; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Infant; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Urinary Tract; Urinary Tract Infections; Uropathogenic Escherichia coli; Young Adult

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenems; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Enterococcus; Fosfomycin; Gram-Positive Bacterial Infections; Humans; Michigan; Microbial Sensitivity Tests; Urinary Tract Infections; Vancomycin Resistance

Vancomycin-resistant (VR) enterococci (VRE) are increasingly important nosocomial pathogens, commonly causing catheter-related urinary tract infections or vascular catheter-related bloodstream infections. In this study, 10 Enterococcus faecium and 9 Enterococcus faecalis different pulsed-field gel electrophoresis genome-type VR clinical isolates were detected. The potential role of fosfomycin-based combination regimens for biofilm-related VRE infection is in vitro evaluated. Anti-VRE activities of fosfomycin, ampicillin, linezolid, minocycline, rifampicin, tigecycline, teicoplanin, vancomycin alone, or fosfomycin-based combinations were studied by time-kill method and a biofilm model. Of the fosfomycin-based combinations, a synergistic effect was particularly noted for teicoplanin against 89% of the VR E. faecalis isolates. In a biofilm model, only linezolid alone was able to reduce the bacterial loads, and the use of fosfomycin-based combinations, excluding rifampicin (40%), failed to enhance antibacterial activity against VR E. faecium. For E. faecalis, an inhibitory effect was evident using ampicillin alone or fosfomycin plus rifampicin (100%), tigecycline (56%), or teicoplanin (44%). However, an antagonistic effect was found for ampicillin plus fosfomycin against 2 of 3 of the VR E. faecalis isolates. The antibacterial activities of the drugs tested against VRE in vitro varied by species. Ampicillin exhibited potential activity against planktonic- and biofilm-embedded VR E. faecalis. Fosfomycin-based combinations may have enhanced antibacterial effects against VRE even in the biofilm model, and this observation warrants further clinical studies.

Topics: Anti-Bacterial Agents; Drug Synergism; Enterococcus faecalis; Enterococcus faecium; Fosfomycin; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Microbial Viability; Vancomycin Resistance

Fosfomycin is a potential option for vancomycin-resistant enterococcus (VRE) infections despite limited in vitro and clinical data. In this study, 32 VRE isolates from renal transplant patients with urinary stent infections were susceptible to fosfomycin, daptomycin, and linezolid and resistant to amoxicillin, minocycline, and nitrofurantoin based on their MIC(50)s and MIC(90)s. Fosfomycin was bacteriostatic at 0.5 to 16× the MIC (32 to 2,048 μg/ml); synergy occurred when fosfomycin was combined with daptomycin (2.8 to 3.9 log(10) CFU/ml kill; P < 0.001) or amoxicillin (2.6 to 3.4; P < 0.05). These combinations may be potent options to treat VRE urinary infections pending investigation of clinical efficacy.

Topics: Acetamides; Amoxicillin; Anti-Bacterial Agents; Daptomycin; Drug Synergism; Enterococcus faecium; Fosfomycin; Gram-Positive Bacterial Infections; Humans; Kidney Transplantation; Linezolid; Microbial Sensitivity Tests; Oxazolidinones; Stents; Urinary Tract; Urinary Tract Infections; Vancomycin; Vancomycin Resistance

Forty-seven vancomycin-resistant Enterococcus (VRE) strains were isolated from clinical samples in 13 Zhejiang hospitals and fecal samples from ICU patients in a large teaching hospital in China. No VRE isolates were detected in healthy human subjects. CC17 was the main clonal complex in clinical Enterococcus faecium isolates but not in isolates from healthy human subjects. Novel vancomycin-resistance transposons were detected among VRE strains. This is the first report demonstrating insertion of tnpA and fosB genes in the vanRS-vanH intergenic region of Tn1546 leading to coresistance to vancomycin and fosfomycin. The four plasmid replicon types (pRUM, pRE25, pEF418, and pB82) were more common in VRE isolates, suggesting their association with vancomycin resistance and nosocomial transmission. The prevalence rate of vancomycin-resistant Staphylococcus aureus-related Inc18-like plasmid, pIP501, in VRE was 21.3%. The prevalence of the esp gene among VRE isolates was high (76.6%). In several VRE strains, the esp and hyl genes were cotransferred with the vanA gene by conjugation. Although the frequency of VRE is low in Chinese hospitals, its association with virulence determinants, the vancomycin-resistance transposon with other resistance gene insertions or plasmids may lead to multidrug resistance and the evolution of pathogenic VRE.

Topics: Anti-Bacterial Agents; Bacterial Proteins; China; Conjugation, Genetic; DNA Transposable Elements; Enterococcus; Fosfomycin; Gram-Positive Bacterial Infections; Hospitals, Teaching; Humans; Incidence; Microbial Sensitivity Tests; Plasmids; Replicon; Vancomycin Resistance; Virulence Factors

Guideline recommendations on therapy in urinary tract infections are based on antibiotic resistance rates. Due to a lack of surveillance data, little is known about resistance rates in uncomplicated urinary tract infection (UTI) in general practice in Germany. In a prospective observational study, urine cultures of all women presenting with urinary tract infections in general practice were analysed. Resistance rates against antibiotics recommended in German guidelines on UTI are presented.. In a prospective, multi-center observational study general practitioner included all female patients ≥ 18 years with clinically suspected urinary tract infection. Only patients receiving an antibiotic therapy within the last two weeks were excluded.. 40 practices recruited 191 female patients (mean age 52 years; range 18-96) with urinary tract infections. Main causative agent was Escherichia coli (79%) followed by Enterococcus faecalis (14%) and Klebsiella pneumoniae (7.3%).Susceptibility of E.coli as the main causative agent was highest against fosfomycin and nitrofurantoin, with low resistance rates of 4,5%; 2,2%. In 17,5%, E.coli was resistant to trimethoprim and in 8,5% to ciprofloxacin.. Resistance rates of uropathogens from unselected patients in general practice differ from routinely collected laboratory data. These results can have an impact on antibiotic prescribing and treatment recommendations.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Ciprofloxacin; Drug Resistance, Bacterial; Escherichia coli Infections; Female; Fosfomycin; General Practice; Germany; Gram-Positive Bacterial Infections; Humans; Klebsiella Infections; Microbial Sensitivity Tests; Middle Aged; Nitrofurantoin; Prospective Studies; Trimethoprim; Urinary Tract Infections; Young Adult

Topics: Actinobacteria; Aged, 80 and over; Amoxicillin; Anti-Bacterial Agents; Drug Resistance, Bacterial; Fosfomycin; Gram-Positive Bacterial Infections; Humans; Male; Urinary Retention; Urinary Tract Infections

In 2004-2008, the epidemiological and clinical Infective Endocarditis Study Group (SEI) evaluated 852 cases of infective endocarditis. Staphylococcus aureus was the main involved pathogen (24.5%) and Enterococcus faecalis etiology was described in 11% of the cases. The aim of this study was to evaluate the in vitro activity of 12 antibiotics alone and in association against 27 strains of E. faecalis isolated from blood cultures of patients with infective endocarditis.. The results showed high in vitro activity of tigecycline, daptomycin and linezolid. A high synergistic effect was obtained with the association ceftriaxone-fosfomycin [fractional inhibitory concentration (FIC)(50) = 0.34, FIC(90) = 0.78]. Furthermore, ceftriaxone plus ampicillin presented additive results (FIC(50) = 0.66, FIC(90) = 1.00), and ceftriaxone plus fosfomycin and ceftriaxone plus ampicillin were significantly more active in vitro than each drug alone. The efficacy of ceftriaxone plus fosfomycin was confirmed by the association testing using the broth dilution technique.. Fosfomycin seems particularly significant and its association with ceftriaxone could be considered as a useful therapeutic option in medical treatment of E. faecalis infective endocarditis.

Topics: Animals; Anti-Bacterial Agents; Ceftriaxone; Drug Synergism; Drug Therapy, Combination; Endocarditis; Enterococcus faecalis; Fosfomycin; Gram-Positive Bacterial Infections; Humans; Italy; Microbial Sensitivity Tests; Sheep

We aimed to evaluate the antimicrobial activity of fosfomycin against Gram-positive non-urinary isolates collected at the microbiological laboratory of the University Hospital of Heraklion, Crete, Greece, in 2008. Susceptibility testing was performed by the disk diffusion method for a total of 1846 isolates; 1275 isolates (69.1%) were susceptible to fosfomycin. Specifically, 416/419 Staphylococcus aureus (99.3%) [including 129/130 meticillin-resistant S. aureus (MRSA) isolates] and 745/961 coagulase-negative staphylococci (77.5%) were susceptible to fosfomycin. Among 42 Streptococcus pneumoniae, 64 Streptococcus pyogenes and 93 other streptococcal isolates, 61.9%, 40.6% and 48.4%, respectively, were susceptible to fosfomycin. Fosfomycin was inactive against the 166 enterococcal isolates tested. This old antibiotic may deserve consideration for further studies and use in clinical practice, especially for S. aureus (including MRSA) infections.

Topics: Anti-Bacterial Agents; Enterococcus; Fosfomycin; Gram-Positive Bacterial Infections; Greece; Hospitals; Humans; Microbial Sensitivity Tests; Staphylococcus; Streptococcus

Topics: Anti-Bacterial Agents; Bacteriuria; Enterococcus; Escherichia coli; Female; Follow-Up Studies; Fosfomycin; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Proteus

Topics: Acetamides; Cross Infection; Enterococcus faecium; Fosfomycin; Gram-Positive Bacterial Infections; Humans; Linezolid; Microbial Sensitivity Tests; Oxazolidinones; Vancomycin Resistance

The in vivo activity of the combination of daptomycin and fosfomycin against a beta-lactamase-producing, highly gentamicin-resistant strain of Enterococcus faecalis in a relapse model of rat endocarditis was studied. Minimum inhibitory concentrations (MICs) (micrograms per milliliter) for these agents against this strain were 4 (daptomycin) and 16 (fosfomycin). Time-kill studies demonstrated synergistic bactericidal activity when daptomycin (0.5 micrograms/ml) and fosfomycin (32 micrograms/ml) were combined. There was no significant difference between the number of valves sterilized by daptomycin alone [six (35%) of 17 valves sterilized] and daptomycin+fosfomycin [ten (59%) of 17 valves sterilized] p = 0.3. These results suggest that the in vitro bactericidal synergism demonstrable between these two agents against strains of enterococci will not necessarily translate into greater therapeutic efficacy in clinical infections.

Topics: Animals; Daptomycin; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Endocarditis, Bacterial; Enterococcus faecalis; Fosfomycin; Gram-Positive Bacterial Infections; Male; Microbial Sensitivity Tests; Peptides; Rats; Rats, Inbred Strains