fosfomycin and Shock--Septic

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

We employed an in-vivo pharmacokinetic/in-vitro pharmacodynamic method to simulate bacterial killing in plasma and the interstitium of skeletal muscle tissue after intravenous administration of 2 g of cefpirome and 8 g of fosfomycin alone and in combination to patients with sepsis. Interstitial antimicrobial concentrations were determined by use of in-vivo microdialysis. CFU/ml of Staphylococcus aureus (ATCC 29213) and Pseudomonas aeruginosa (clinical isolate) decreased by approximately 2log(10) for plasma and muscle tissue 6 h after cefpirome and fosfomycin administration compared with the baseline, respectively. The simulation of plasma and tissue pharmacokinetics for the combined administration of these antibiotics resulted in complete eradication of S. aureus within 5 h after drug exposure. No bacterial re-growth occurred in any of the simulations within 6 h. The in-vitro simulation of in-vivo plasma and tissue pharmacokinetics of cefpirome and fosfomycin has shown that both antimicrobial agents kill S. aureus and P. aeruginosa strains effectively after single dose administration. This effect was most pronounced by the combined use of these antimicrobial agents. Therefore, this data corroborates antimicrobial strategies of simultaneous administration of cefpirome and fosfomycin in patients with severe soft tissue infection.

Topics: Anti-Bacterial Agents; Cefpirome; Cephalosporins; Colony Count, Microbial; Drug Therapy, Combination; Fosfomycin; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Shock, Septic; Staphylococcus aureus

Therapeutic effects of fosfomycin (FOF) and imipenem (IPM) were investigated in a novel model for endotoxin shock that was caused by intraperitoneal (i.p.) infection with 10(8) colony forming units of attenuated Salmonella typhimurium. Acute lethal shock was observed in BALB/c and ddY but not in lipopolysaccharide (LPS)-nonresponder BALB/lps(d) mice. Effects of FOF, but not its enantiomer, and IPM were dose- and time-dependent, since therapeutic efficacy was demonstrated in mice injected i.p. or orally at doses of more than 20 mg/kg 15 min before or 1 h after infection. Treatment with FOF 1 h postinfection (p.i.) resulted in significant decreases in bacterial numbers in spleen and liver, suggesting that the antimicrobial activity of FOF seems to closely correlate to suppression of infection-induced lethal shock. Regarding coagulation systems, FOF inhibited increase in the prothrombin time but upregulated fibrinogen concentration. Plasma levels of LPS released from bacilli were significantly higher in FOF- than IPM-treated mice and infection controls, but both antibiotics showed similar efficacy in protection.

Topics: Animals; Dose-Response Relationship, Drug; Female; Fosfomycin; Mice; Mice, Inbred BALB C; Salmonella Infections, Animal; Salmonella typhimurium; Shock, Septic; Time Factors

Varicella is a common viral infection which is generally benign in infancy and has a good outcome. It may sometimes be complicated by severe group A streptococcal superinfection.. Three days after the beginning of varicella, a previously healthy 2-year-old girl presented with left leg pain, lameness and edema of all four limbs. Toxic shock syndrome occurred, due to beta-hemolytic group A Streptococcus grown from blood culture. Computerized tomography (CT) scan showed a mild effusion involving both hips. Cefotaxim was administered, but the week after magnetic resonance imaging (MRI) showed a necrotizing fasciitis and a lesion of the left leg leading to a patchy femoral diaphysis consistent with osteomyelitis. Joint aspirate culture did not grow. The left leg was immobilized in plaster for 6 weeks and the child was given cefotaxim and fosfomycin parenterally during 30 days, then followed by 45 days of oral amoxicillin. She recovered without sequelae.. Group A Streptococcus infection is a dangerous complication of varicella. It must be considered in case of any joint pain occurring during or just after this disease. The choice of the best treatment needs full collaboration between surgeons, radiologists and pediatricians.

Topics: Cefotaxime; Chickenpox; Child, Preschool; Drug Therapy, Combination; Female; Fosfomycin; Humans; Shock, Septic; Streptococcal Infections; Streptococcus pyogenes

We present a case of toxic shock syndrome (TSS) induced by MRSA after sinus surgery. The patient was a 64-year-old woman who had undergone sinus surgery because of chronic sinusitis. Nine days after the surgery, she began to have sore throat, fever, and diffuse erythroderma followed by severe hypotension and renal dysfunction. Culture of sputum, nasal discharge and stool showed MRSA. Blood culture was negative. She was treated with intravenous fluids, catecholamines and antibiotics (vancomycin and fosfomycin). Continuous hemodiafiltration was started because of oliguria. Her condition improved gradually and she was discharged about a month after the onset of her illness. We should recognize that TSS can occur as a fatal complication after nasal surgery.

Topics: Chronic Disease; Drug Therapy, Combination; Female; Fosfomycin; Hemodiafiltration; Humans; Methicillin Resistance; Middle Aged; Postoperative Complications; Shock, Septic; Sinusitis; Staphylococcal Infections; Vancomycin

In the years 1970 to 1979 312 patients with purulent meningitis were treated at the University of Innsbruck, Department of Pediatrics. The overall fatality rate was 16%, the majority of fatal cases were due to gram negative organisms before 1977. The mortality rate of meningococcal meningitis due to H. influenzae was 5.6 and 1.6%, respectively and compares very well to reports in the literature. 12% of children are severely handicapped. Hearing impairment is the most frequent cause of retardation with 6.8%. We compared therapeutic results of two different treatment regimen in our clinic with the therapeutic results in other centers reported in the literature. The combination of ampicillin and chloramphenicol was superior to other treatment modalities particularly ampicillin monotherapy in H. influenzae meningitis and meningitis due to unknown organisms. Theoretical reservations against this combination have been eliminated by the proof of the bactericidal action of chloramphenicol against the most common meningeal pathogens and the synergistic action with beta lactam antibiotics. In pneumococcal meningitis the administration of high doses of Na-Penicillin G as i. v. bolus proved to be connected with unexpected complications and fatalities. The administration of 25000-40000 E Na Penicillin G as an i. v. infusion over 1 hour 4--6 times daily was a less hazardous yet effective therapy. Unsatisfying results in the treatment of gram negative meningitis in neonates prompted the investigation of a new compound fosfomycin for this indication. In vitro investigation of the antimicrobial activity against 68 meningeal pathogens and investigation of this drug in a lapine model showed encouraging results. In the last years a limited clinical trial in severely affected newborn infants was done with promising therapeutic efficacy. A larger scale investigation of this drug is now proceeding in form of a National cooperative Study of gram negative meningitis in Austria. Besides an effective antimicrobial treatment particular attention has to be paid to an adequate fluid and electrolyte replacement. Symptomatic therapy of complications e. g. seizures as well as continuous close monitoring of all vital signs is mandatory for optimal therapeutic success. Subdural effusions have been observed infrequently and only diagnostic subdural punctures have been performed.

Topics: Ampicillin; Child; Child, Preschool; Chloramphenicol; Cortisone; Electrolytes; Fluid Therapy; Fosfomycin; Humans; Infant; Meningitis; Meningitis, Haemophilus; Meningitis, Pneumococcal; Penicillin G; Prognosis; Shock, Septic