fosfomycin and Endocarditis--Bacterial

Infective endocarditis is a microbial infection of the endocardial surface of the heart. Antibiotics are the cornerstone of treatment, but due to the differences in presentation, populations affected, and the wide variety of micro-organisms that can be responsible, their use is not standardised. This is an update of a review previously published in 2016.. To assess the existing evidence about the clinical benefits and harms of different antibiotics regimens used to treat people with infective endocarditis.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase Classic and Embase, LILACS, CINAHL, and the Conference Proceedings Citation Index - Science on 6 January 2020. We also searched three trials registers and handsearched the reference lists of included papers. We applied no language restrictions.. We included randomised controlled trials (RCTs) assessing the effects of antibiotic regimens for treating definitive infective endocarditis diagnosed according to modified Duke's criteria. We considered all-cause mortality, cure rates, and adverse events as the primary outcomes. We excluded people with possible infective endocarditis and pregnant women.. Two review authors independently performed study selection, 'Risk of bias' assessment, and data extraction in duplicate. We constructed 'Summary of findings' tables and used GRADE methodology to assess the quality of the evidence. We described the included studies narratively.. Six small RCTs involving 1143 allocated/632 analysed participants met the inclusion criteria of this first update. The included trials had a high risk of bias. Three trials were sponsored by drug companies. Due to heterogeneity in outcome definitions and different antibiotics used data could not be pooled. The included trials compared miscellaneous antibiotic schedules having uncertain effects for all of the prespecified outcomes in this review. Evidence was either low or very low quality due to high risk of bias and very low number of events and small sample size. The results for all-cause mortality were as follows: one trial compared quinolone (levofloxacin) plus standard treatment (antistaphylococcal penicillin (cloxacillin or dicloxacillin), aminoglycoside (tobramycin or netilmicin), and rifampicin) versus standard treatment alone and reported 8/31 (26%) with levofloxacin plus standard treatment versus 9/39 (23%) with standard treatment alone; risk ratio (RR) 1.12, 95% confidence interval (CI) 0.49 to 2.56. One trial compared fosfomycin plus imipenem 3/4 (75%) versus vancomycin 0/4 (0%) (RR 7.00, 95% CI 0.47 to 103.27), and one trial compared partial oral treatment 7/201 (3.5%) versus conventional intravenous treatment 13/199 (6.53%) (RR 0.53, 95% CI 0.22 to 1.31). The results for rates of cure with or without surgery were as follows: one trial compared daptomycin versus low-dose gentamicin plus an antistaphylococcal penicillin (nafcillin, oxacillin, or flucloxacillin) or vancomycin and reported 9/28 (32.1%) with daptomycin versus 9/25 (36%) with low-dose gentamicin plus antistaphylococcal penicillin or vancomycin; RR 0.89, 95% CI 0.42 to 1.89. One trial compared glycopeptide (vancomycin or teicoplanin) plus gentamicin with cloxacillin plus gentamicin (13/23 (56%) versus 11/11 (100%); RR 0.59, 95% CI 0.40 to 0.85). One trial compared ceftriaxone plus gentamicin versus ceftriaxone alone (15/34 (44%) versus 21/33 (64%); RR 0.69, 95% CI 0.44 to 1.10), and one trial compared fosfomycin plus imipenem versus vancomycin (1/4 (25%) versus 2/4 (50%); RR 0.50, 95% CI 0.07 to 3.55). The included trials reported adverse events, the need for cardiac surgical interventions, and rates of uncontrolled infection, congestive heart failure, relapse of endocarditis, and septic emboli, and found no conclusive differences between groups (very low-quality evidence). No trials assessed quality of life.. This first update confirms the findings of the original version of the review. Limited and low to very low-quality evidence suggests that the comparative effects of different antibiotic regimens in terms of cure rates or other relevant clinical outcomes are uncertain. The conclusions of this updated Cochrane Review were based on few RCTs with a high risk of bias. Accordingly, current evidence does not support or reject any regimen of antibiotic therapy for the treatment of infective endocarditis.

Topics: Anti-Bacterial Agents; Endocarditis, Bacterial; Female; Fosfomycin; Humans; Imipenem; Levofloxacin; Male; Penicillins; Randomized Controlled Trials as Topic; Vancomycin

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

The treatment of multidrug-resistant (MDR), extensively drug-resistant or pandrug-resistant non-fermenting Gram-negative bacterial infections constitutes a challenge in an era of few new antibiotic choices. This mandates the re-evaluation of already existing antibiotics such as fosfomycin. We systematically reviewed the literature to assess the clinical and microbiological effectiveness of fosfomycin in the treatment of these infections by searching PubMed, Scopus and the Cochrane Library databases. In 23 microbiological studies identified, 1859 MDR non-fermenting Gram-negative bacterial isolates were examined. The susceptibility rate to fosfomycin of MDR Pseudomonas aeruginosa isolates was >or=90% and 50-90% in 7/19 and 4/19 relevant studies, respectively. Cumulatively, 511/1693 (30.2%) MDR P. aeruginosa isolates were susceptible to fosfomycin. Serotype O12 isolates exhibited greater susceptibility. Only 3/85 (3.5%) MDR Acinetobacter baumannii and 0/31 MDR Burkholderia spp. isolates were susceptible to fosfomycin. Variable criteria of susceptibility were used in the included studies. Fosfomycin was synergistic in combination with a beta-lactam, aminoglycoside or ciprofloxacin in 46/86 (53.5%) MDR P. aeruginosa isolates. One animal study found a good therapeutic effect of the combination fosfomycin/gentamicin against MDR P. aeruginosa endocarditis. In six clinical studies, 33 patients with MDR P. aeruginosa infections (mainly pulmonary exacerbations of cystic fibrosis) received fosfomycin (25/33 in combination with other antibiotics); 91% of the patients clinically improved. In conclusion, fosfomycin could have a role as a therapeutic option against MDR P. aeruginosa infections. Further research is needed to clarify the potential utility of this agent.

Topics: Acinetobacter baumannii; Animals; Anti-Bacterial Agents; Burkholderia; Drug Resistance, Multiple, Bacterial; Drug Synergism; Endocarditis, Bacterial; Fosfomycin; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections

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

A prospective clinical study was carried out to assess the adequacy of perioperative antibiotic prophylaxis using fosfomycin in patients undergoing open-heart surgery for valve diseases for the prevention of early postoperative endocarditis, as well as for serious mediastinal infections that are caused mostly by multiresistant staphylococci and Gram-negative bacteria. Perioperative pharmacokinetics and tissue penetration were determined within the harvested heart valves and subcutaneous tissue. Reliable bactericidal serum levels were established at the first measurement 10 min after the end of intravenous infusion (203.7 +/- 44.7 micrograms/ml) and were maintained during surgery for at least 120 min (124.6 +/- 58.4 micrograms/ml), even in cases of prolonged extracorporeal circulation. Cardiopulmonary bypass did not alter the serum elimination of fosfomycin in comparison with patients not undergoing extracorporeal circulation. Peak tissue concentrations were achieved in both aortic and mitral valves after 30 min, ranging between 27.1 and 76.9 micrograms/g for aortic valves and 39.6-69.4 micrograms/g for mitral valves, depending on the degree of valvular degeneration. MIC values of 16 micrograms/g were maintained in both valves for at least up to 60 min. There was no evidence of renal impairment, adverse reactions or infections during the postoperative course or thereafter for a period of 3 months. It is concluded that perioperative intravenous antibiotic prophylaxis using fosfomycin (5 g t.i.d. in adults), beginning with induction of anesthesia and continued for 48 h postoperatively, provides rapid, reliable bactericidal serum levels and valvular tissue concentrations that will inhibit most Gram-positive and Gram-negative organisms that cause bacterial endocarditis and other serious infections following cardiac surgery.

Topics: Aged; Aortic Valve; Endocarditis, Bacterial; Extracorporeal Circulation; Female; Fosfomycin; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Male; Mediastinitis; Metabolic Clearance Rate; Middle Aged; Mitral Valve; Prospective Studies; Surgical Wound Infection

In vitro and in vivo activity of daptomycin alone or plus either cloxacillin or fosfomycin compared with cloxacillin alone and cloxacillin plus gentamicin were evaluated in a rabbit model of MSSA experimental endocarditis (EE).. Five MSSA strains were used in the in vitro time-kill studies at standard (105-106 cfu/mL) and high (108 cfu/mL) inocula. In the in vivo EE model, the following antibiotic combinations were evaluated: cloxacillin (2 g/4 h) alone or combined with gentamicin (1 mg/kg/8 h) or daptomycin (6 mg/kg once daily); and daptomycin (6 mg/kg/day) alone or combined with fosfomycin (2 g/6 h).. At standard and high inocula, daptomycin plus fosfomycin or cloxacillin were bactericidal against 4/5 and 5/5 strains, respectively, while cloxacillin plus gentamicin was bactericidal against 3/5 strains at standard inocula but against none at high inocula. Fosfomycin, cloxacillin, gentamicin and daptomycin MIC/MBCs of the MSSA-678 strain used in the EE model were: 8/64, 0.25/0.5, 0.25/0.5 and 1/8 mg/L, respectively. Adding gentamicin to cloxacillin significantly reduced bacterial density in vegetations compared with cloxacillin monotherapy (P = 0.026). Adding fosfomycin or cloxacillin to daptomycin [10/11 (93%) and 8/11 (73%), respectively] significantly improved the efficacy of daptomycin in sterilizing vegetations [0/11 (0%), P < 0.001 for both combinations] and showed better activity than cloxacillin alone [0/10 (0%), P < 0.001 for both combinations] and cloxacillin plus gentamicin [3/10 (30%), P = 0.086 for cloxacillin plus daptomycin and P = 0.008 for fosfomycin plus daptomycin]. No recovered isolates showed increased daptomycin MIC.. The addition of cloxacillin or fosfomycin to daptomycin is synergistic and rapidly bactericidal, showing better activity than cloxacillin plus gentamicin for treating MSSA EE, supporting their clinical use.

Topics: Animals; Anti-Bacterial Agents; Cloxacillin; Daptomycin; Endocarditis; Endocarditis, Bacterial; Fosfomycin; Gentamicins; Microbial Sensitivity Tests; Rabbits

The urgent need of effective therapies for methicillin-resistant Staphylococcus aureus (MRSA) infective endocarditis (IE) is a cause of concern. We aimed to ascertain the in vitro and in vivo activity of the older antibiotic fosfomycin combined with different beta-lactams against MRSA and glycopeptide-intermediate-resistant S. aureus (GISA) strains. Time-kill tests with 10 isolates showed that fosfomycin plus imipenem (FOF+IPM) was the most active evaluated combination. In an aortic valve IE model with two strains (MRSA-277H and GISA-ATCC 700788), the following intravenous regimens were compared: fosfomycin (2 g every 8 h [q8h]) plus imipenem (1 g q6h) or ceftriaxone (2 g q12h) (FOF+CRO) and vancomycin at a standard dose (VAN-SD) (1 g q12h) and a high dose (VAN-HD) (1 g q6h). Whereas a significant reduction of MRSA-227H load in the vegetations (veg) was observed with FOF+IPM compared with VAN-SD (0 [interquartile range [IQR], 0 to 1] versus 2 [IQR, 0 to 5.1] log CFU/g veg; P = 0.01), no statistical differences were found with VAN-HD. In addition, FOF+IPM sterilized more vegetations than VAN-SD (11/15 [73%] versus 5/16 [31%]; P = 0.02). The GISA-ATCC 700788 load in the vegetations was significantly lower after FOF+IPM or FOF+CRO treatment than with VAN-SD (2 [IQR, 0 to 2] and 0 [IQR, 0 to 2] versus 6.5 [IQR, 2 to 6.9] log CFU/g veg; P < 0.01). The number of sterilized vegetations after treatment with FOF+CRO was higher than after treatment with VAN-SD or VAN-HD (8/15 [53%] versus 4/20 [20%] or 4/20 [20%]; P = 0.03). To assess the effect of FOF+IPM on penicillin binding protein (PBP) synthesis, molecular studies were performed, with results showing that FOF+IPM treatment significantly decreased PBP1, PBP2 (but not PBP2a), and PBP3 synthesis. These results allow clinicians to consider the use of FOF+IPM or FOF+CRO to treat MRSA or GISA IE.

Topics: Animals; Anti-Bacterial Agents; Aortic Valve; Area Under Curve; Ceftriaxone; Drug Administration Schedule; Drug Combinations; Drug Resistance, Bacterial; Drug Synergism; Endocarditis, Bacterial; Fosfomycin; Gene Expression; Imipenem; Infusion Pumps; Methicillin-Resistant Staphylococcus aureus; Penicillin-Binding Proteins; Protein Isoforms; Rabbits; Staphylococcal Infections; Vancomycin

Topics: Aged, 80 and over; Anti-Bacterial Agents; Aortic Valve Insufficiency; Atrial Fibrillation; Daptomycin; Dose-Response Relationship, Drug; Drug Therapy, Combination; Dyspnea; Endocarditis, Bacterial; Female; Fosfomycin; Heart Failure; Hepatitis C, Chronic; Humans; Prosthesis-Related Infections; Sodium; Staphylococcal Infections

We describe 3 patients with left-sided staphylococcal endocarditis (1 with methicillin-susceptible Staphylococcus aureus [MSSA] prosthetic aortic valve endocarditis and 2 with methicillin-resistant S. aureus [MRSA] native-valve endocarditis) who were successfully treated with high-dose intravenous daptomycin (10 mg/kg/day) plus fosfomycin (2 g every 6 h) for 6 weeks. This combination was tested in vitro against 7 MSSA, 5 MRSA, and 2 intermediately glycopeptide-resistant S. aureus isolates and proved to be synergistic against 11 (79%) strains and bactericidal against 8 (57%) strains. This combination deserves further clinical study.

Topics: Aged; Anti-Bacterial Agents; Daptomycin; Drug Synergism; Drug Therapy, Combination; Endocarditis, Bacterial; Female; Fosfomycin; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Staphylococcal Infections

Emergence of daptomycin-nonsusceptible (DNS) Staphylococcus aureus is a dreadful problem in the treatment of endocarditis. Few current therapeutic agents are effective for treating infections caused by DNS S. aureus.. We describe the emergence of DNS S. aureus. in a patient with implantable cardioverter-defibrillator (ICD) device -related endocarditis who was priorily treated with daptomycin. Metastatic dissemination as osteomyelitis further complicated the management of endocarditis. The dilemma was successfully managed by surgical removal of the ICD device and combination antimicrobial therapy with high-dose daptomycin and fosfomycin.. Surgical removal of intracardiac devices remains an important adjunctive measure in the treatment of endocarditis. Our case suggests that combination therapy is more favorable than single-agent therapy for infections caused by DNS S. aureus.

Topics: Adult; Anti-Bacterial Agents; Daptomycin; Drug Resistance, Bacterial; Drug Therapy, Combination; Endocarditis, Bacterial; Female; Fosfomycin; Humans; Microbial Sensitivity Tests; Staphylococcal Infections; Staphylococcus aureus

Topics: Adult; Aged; Anti-Bacterial Agents; Defibrillators, Implantable; Drug Therapy, Combination; Endocarditis, Bacterial; Female; Fosfomycin; Heart Valve Prosthesis; Humans; Male; Middle Aged; Pacemaker, Artificial; Prosthesis-Related Infections; Renal Insufficiency; Vancomycin

The bactericidal activity of pefloxacin and fosfomycin alone and in combination against Pseudomonas aeruginosa was evaluated in an experimental rabbit endocarditis model after 24 h of treatment. Two strains with intermediate susceptibility to pefloxacin and good susceptibility to fosfomycin were tested. The serum kinetics obtained during administration of 400 mg every 12 h in humans were simulated in the animals using computer-controlled variable-flow infusion. Fosfomycin was administered as a continuous infusion at a constant flow, allowing a steady-state concentration of 47.4 +/- 11.9 mg/ml to be reached in serum. In valvular vegetations, pefloxacin was less bactericidal than fosfomycin, and in combination treatment, it reduced (but did not abolish) the bactericidal effect of fosfomycin. The duration of the pretreatment interval (12-48 h) had a negative effect on the bactericidal activity of both drugs, especially that of fosfomycin.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Disease Models, Animal; Drug Administration Schedule; Drug Therapy, Combination; Endocarditis, Bacterial; Female; Fosfomycin; Half-Life; Humans; Infusions, Intravenous; Pefloxacin; Pseudomonas aeruginosa; Pseudomonas Infections; Rabbits; Random Allocation; Treatment Outcome

The in vivo efficacy of ciprofloxacin or pefloxacin alone or in combination with fosfomycin was evaluated in experimental aortic valve endocarditis induced in 133 rabbits by a multidrug-susceptible or multidrug-resistant strain of Pseudomonas aeruginosa. Therapy was initiated early (12 h after infection), when bacterial counts in aortic valve vegetations were relatively low, or late (48 h after infection), when vegetations contained a larger inoculum. Antibodies were administered as a continuous 24-h intravenous infusion. Mean steady-state levels of ciprofloxacin (64 mg/kg), pefloxacin (64 mg/kg), and fosfomycin (300 mg/kg) in serum were 2.5, 4.2, and 63.9 mg/liter, respectively. For the multidrug-susceptible strain, all regimens except pefloxacin alone significantly reduced the number of CFU per gram of vegetation versus controls, whether treatment was performed early or late. For the multidrug-resistant strain, none of the regimens showed differences from untreated controls, except ciprofloxacin-fosfomycin, which significantly reduced bacterial counts in vegetations compared with controls when therapy was begun early (4.1 +/- 1.1 log10 CFU/g of vegetation; P < 0.001 versus the control). These data suggest that combination of fosfomycin with ciprofloxacin or pefloxacin is more effective than ciprofloxacin or pefloxacin alone for the therapy of severe infections caused by multidrug-susceptible P. aeruginosa.

Topics: Animals; Ciprofloxacin; Drug Resistance, Multiple; Drug Therapy, Combination; Endocarditis, Bacterial; Female; Fosfomycin; Pefloxacin; Pseudomonas Infections; Rabbits

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

Topics: Animals; Disease Models, Animal; Endocarditis, Bacterial; Fosfomycin; Gentamicins; Humans; Methicillin Resistance; Microbial Sensitivity Tests; Rabbits; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

The authors studied the activity of fosfomycin (FOS) and/or gentamicin (GEN) against a Klebsiella pneumoniae strain resistant to all beta-lactams--except cephamycins and imipenem--by production of a plasmid mediated extended broad-spectrum beta-lactamase-TEM-3, to all aminoglycosides--except gentamicin--by production of a plasmid mediated 6' aminoglycoside acetyltransferase IV, to sulfonamides and to tetracyclines. In vitro, the combination FOS (MIC = MBC = 32 mg/l) + GEN (MIC = MBC = 2) appeared indifferent (FIC = 0.75; FBC = 1). In vivo, on experimental endocarditis in rabbits, FOS alone was ineffective, GEN alone was active but only at high dose regimen, FOS - GEN combination was active as compared with controls. Fosfomycin - gentamicin combination may be an alternative in the therapy of severe infections due to multiresistant Enterobacteriacae.

Topics: Animals; beta-Lactamases; Drug Resistance, Microbial; Drug Therapy, Combination; Endocarditis, Bacterial; Female; Fosfomycin; Gentamicins; In Vitro Techniques; Klebsiella Infections; Klebsiella pneumoniae; Rabbits

A case of infective endocarditis caused by methicillin-resistant Staphylococcus aureus (MRSA) was successfully treated with a combination therapy with cefmetazole (CMZ) and fosfomycin (FOM). A 55 year old man was admitted to the Keio Hospital because of fever of unknown origin. Physical examination revealed blood pressure of 132/62 mmHg, heart rate of 118/min and body temperature of 39.8 degrees C. Diastolic regurgitant murmur (Levine II/VI) was heard at the left sternal border on the third intercostal space. Chest X-ray showed mild cardiomegaly. Two dimensional echocardiography and color flow mapping demonstrated mildly dilated and hyperkinetic left ventricle, redundant aortic valve, giant vegetation from the aortic valve and severe aortic regurgitation. MRSA was isolated from the blood of this patient. Bacteriostatic synergism between CMZ and FOM against S. aureus isolated from the blood of this patient was detected both by the Kirby-Bauer method and by the checker-board method. The combination therapy with CMZ and FOM cleared the clinical symptoms and normalized the inflammatory reactions. No relapse was observed for at least 10 months. We concluded that the combination therapy with CMZ and FOM was invaluable for the treatment of infections endocarditis by MRSA.

Topics: Cefmetazole; Drug Evaluation; Drug Therapy, Combination; Endocarditis, Bacterial; Fosfomycin; Humans; Male; Methicillin; Middle Aged; Penicillin Resistance; Staphylococcal Infections

The efficacies of pefloxacin, fosfomycin, and both of these agents in combination against methicillin-resistant Staphylococcus aureus were assessed in a rat endocarditis model. The combination prevented emergence of the fosfomycin and pefloxacin resistance seen in 36 and 4%, respectively, of animals receiving either agent alone and was more effective than either agent in sterilizing cardiac vegetations.

Topics: Animals; Anti-Infective Agents; Endocarditis, Bacterial; Fosfomycin; Male; Methicillin; Norfloxacin; Pefloxacin; Penicillin Resistance; Rats; Rats, Inbred Strains; Staphylococcal Infections

The efficacy of fosfomycin in combination with vancomycin or gentamicin was evaluated in experimental endocarditis caused by methicillin-resistant Staphylococcus aureus. After 5 days of therapy, both combinations proved to be highly effective since all rabbits had sterile vegetations.

Topics: Animals; Drug Therapy, Combination; Endocarditis, Bacterial; Fosfomycin; Gentamicins; Methicillin; Penicillin Resistance; Rabbits; Staphylococcus aureus; Vancomycin

Topics: Drug Therapy, Combination; Endocarditis, Bacterial; Female; Fosfomycin; Gentamicins; Haemophilus Infections; Humans; Middle Aged

The effectiveness of fosfomycin in combination with other antibiotics was studied in vitro and in the treatment of left-sided endocarditis in rabbits caused by S. sanguis, S. faecalis, S. aureus or P. aeruginosa. In vitro combinations of fosfomycin plus penicillin, fosfomycin plus cloxacillin, and fosfomycin plus amikacin were synergistic against the strains tested. In vivo synergism was also demonstrated since fosfomycin combinations produced a greater reduction in the number of CFU/g of vegetations than the administration of one antibiotic alone.

Topics: Animals; Anti-Bacterial Agents; Drug Evaluation, Preclinical; Drug Synergism; Endocarditis, Bacterial; Fosfomycin; Microbial Sensitivity Tests; Pseudomonas Infections; Rabbits; Staphylococcal Infections; Stem Cells; Streptococcal Infections

Topics: Animals; Endocarditis, Bacterial; Fosfomycin; Methicillin; Penicillin Resistance; Rabbits; Staphylococcal Infections; Staphylococcus epidermidis; Vancomycin

The authors report a case of Staphylococcus epidermidis prosthetic valve endocarditis. After two unsuccessful treatments, the association Gentamicin-Fosfomycin provided adequate serum bactericidal titers and had a good efficacy.

Topics: Drug Therapy, Combination; Endocarditis, Bacterial; Fosfomycin; Gentamicins; Heart Valve Prosthesis; Humans; Male; Middle Aged; Mitral Valve; Staphylococcal Infections; Staphylococcus epidermidis

The effectiveness of penicillin G, fosfomycin, and cefoxitin alone and in combination was studied in vitro and in the treatment of left-sided Streptococcus sanguis endocarditis in rabbits. In vitro, the combinations penicillin G plus fosfomycin, penicillin G plus cefoxitin, and fosfomycin plus cefoxitin were synergistic or partially synergistic for S sanguis. Therapy with the combinations was more effective in eradicating the species from cardiac vegetations that was that with each antibiotic used alone.

Topics: Animals; Anti-Bacterial Agents; Cefoxitin; Drug Synergism; Drug Therapy, Combination; Endocarditis, Bacterial; Female; Fosfomycin; Humans; Penicillin G; Rabbits; Streptococcal Infections; Streptococcus sanguis