fosfomycin and Meningitis

Four cases of postoperative meningitis caused by methicillin-resistant Staphylococcus aureus (MRSA) are reported together with a review of the literature. These 4 cases were treated successfully by intravenous administration of minomycin, fosfomycin, and cefmetazole. Factors associated with the development of meningitis included multiple craniotomies, the presence of ventricular drainage or a ventriculo-peritoneal shunt, and irradiation.

Topics: Adult; Cefmetazole; Drug Therapy, Combination; Fosfomycin; Humans; Injections, Intravenous; Male; Meningitis; Methicillin Resistance; Middle Aged; Minocycline; Postoperative Complications; Staphylococcal Infections; Staphylococcus aureus

The treatment of infectious complications of implanted foreign bodies into the CNS is unsatisfactory. In the majority of these patients staphylococci are responsible for these infections which elicit only a smoldering inflammatory response with poor penetration of antibiotics into the CSF. It is also very difficult to eradicate staphylococci from the surface of silastic material by antibiotics. Fosfomycin was investigated in the treatment of CSF infections in patients with infected ventriculoatrial shunts. Fosfomycin exhibits a potent antimicrobial activity against staphylococci; this drug also showed a favourable penetration into the CSF in moderately inflamed meninges. A 10 days therapeutic course with fosfomycin plus oxacillin or cefamandole and gentamycin in combination with external drainage of the CSF into a closed system made it possible to exchange all parts of the system in one session without reinfection. This procedure was followed by the same antibiotic regimen postoperatively for 10-14 days. Under this treatment schedule therapeutic results have been considerably better compared to previous treatment modalities.

Topics: Cerebrospinal Fluid Shunts; Child; Child, Preschool; Drug Therapy, Combination; Fosfomycin; Gentamicins; Heart Atria; Humans; Infant; Meningitis; Methylmethacrylates; Oxacillin; Penicillins; Peritoneum; Postoperative Complications; Staphylococcal Infections

Thirty-two patients were included in this trial: 22 with staphylococcal meningitis (including 5 methicillin-resistant) and 10 with enterobacterial meningitis. Mean duration of treatment was 14.5 and 15.9 days respectively. The combination was synergistic in vitro against 10 of the 12 strains of Staphylococcus and 5 of the 6 strains of Enterobacteriaceae studied. Bacteriological sterilization occurred in all cases which could be evaluated, and clinical recovery was obtained in 95.2% of patients with staphylococcal meningitis (4 unrelated deaths) and 100% of patients with enterobacterial meningitis (2 deaths). Bactericidal power of the cerebro-spinal fluid, often less than 1/8, was not correlated with effectiveness against Staphylococci. Mean CSF concentrations of cefotaxime, desacetylcefotaxime and fosfomycin on the 2nd and 15th days of treatment were 4, 3.5 and 39.8 mg/l and 2.2, 2.1 and 28.0 mg/l, respectively. Clinical and biological acceptability was satisfactory. There were three cases of superinfection or colonization, by Pseudomonas and Enterobacter.

Topics: Adolescent; Adult; Aged; Cefotaxime; Drug Evaluation; Drug Therapy, Combination; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Fosfomycin; Humans; Male; Meningitis; Microbial Sensitivity Tests; Middle Aged; Prospective Studies; Staphylococcal Infections; Staphylococcus

From 1984 to 1986, 13 patients (10 adults, 3 children) with bacterial meningitis following neurosurgery or traumatism were given ceftriaxone alone 6 times at a dose of 40 mg/kg one IV injection per day, or in association 7 times with fosfomycin at a dose of 200 mg/kg/day, 3 IV perfusions every 4 h. The bacteriological diagnosis was confirmed in 9 cases (3 Staphylococcus aureus, 4 Streptococcus pneumoniae, 1 Klebsiella, 1 Peptococcus). In vitro neither synergy nor antagonism were observed between the two antimicrobial agents. The acute infections episode resolved in all patients except on who died with a negative CSF culture. One superinfection meningitis with Achromobacter was seen. CSF concentrations of ceftriaxone were assayed and found to be comparable with those reported by most authors. Tolerance was excellent for all our patients.

Topics: Adult; Bacterial Infections; Ceftriaxone; Child; Drug Therapy, Combination; Fosfomycin; Humans; Meningitis; Neurosurgery; Postoperative Complications; Skull Fractures

18 neurosurgical patients were given 15 g fosfomycin at 8-hour intervals. Simultaneously serum and cerebrospinal fluid (CSF) concentrations were determined periodically over 8 hrs. In patients with noninflamed meninges the CSF-concentrations ranged between 6.48 and 8.98 micrograms/ml. In patients with meningitis the CSF-levels amounted to 20.28 and 39.80 micrograms/ml. For perioperative short-time prophylaxis and postoperative infections in neurosurgical patients therapeutically relevant fosfomycin levels against Staph. aureus und Staph. epidermidis can be achieved.

Topics: Adolescent; Adult; Blood-Brain Barrier; Drug Resistance; Female; Fosfomycin; Humans; Male; Meningitis; Middle Aged

16 patients with bacterial meningitis following a neurosurgical procedure were given a combination of ceftriaxone and fosfomycin. 8 microorganism were isolated: 2 Staphylococcus epidermidis, 1 Staphylococcus aureus, 1 Neisseria meningitidis, 1 Streptococcus pneumoniae, 1 Haemophilus influenzae, 1 Serratia marcescens and 1 Aeromonas hydrophila. No pathogen was identified in the remaining cases. All of the isolated strains were susceptible to both antibiotics. In vitro, neither synergy nor antagonism were observed between the two antimicrobial agents. The acute infectious episode resolved in all patients. One relapse only was observed, in a patient with meningitis related to a ventricular shunt, and successfully treated by the same therapeutic schedule associated with removal of the tubing. Lastly, CSF concentrations of both antibiotics were assayed and found to be comparable with those reported by most author.

Topics: Adult; Bacterial Infections; Blood-Brain Barrier; Ceftriaxone; Drug Combinations; Female; Fosfomycin; Humans; Male; Meningitis; Neurosurgery; Postoperative Complications

The article reports on the incidence, the conditions of occurrence, possibilities and successes of treatment with certain (combinations of) antibiotics, in dealing with cases of pseudomonas meningitis. The various possible substances used for treatment are discussed. Rates of penetration and CSF concentrations of azlocillin and cefsulodin are stated. Alternative possibilities for treatment are pointed out.

Topics: Aminoglycosides; Anti-Bacterial Agents; Azlocillin; Bacteriological Techniques; Brain Injuries; Cefsulodin; Cephalosporins; Diagnosis, Differential; Fosfomycin; Humans; Meningitis; Penicillins; Polymyxins; Pseudomonas Infections

The purpose of this study was to evaluate the therapeutic effect of cefotaxime (CTX) and fosfomycin (FOS), alone or in combination, in an experimental meningitis, with cerebrospinal fluid (CSF) concentrations of the two antibiotics reproducing those obtained in human CSF during bacterial meningitis. With a dose of 50 mg/kg of CTX and 100 mg/kg of FOS injected i.v. (CTX over 0.5 h and FOS over 3 h), CSF concentrations were comparable to those observed in man. In a series of five rabbits per treatment group, the bacterial population was counted before and after treatment (two doses with a six-hour interval) with CTX, FOS or CTX + FOS (CTX over 0.5 h before the end of FOS infusion). By the 12th hour of treatment, the percentage of bacteria surviving in CSF compared to the initial population was 4.35% for CTX, 0.20% for FOS and 0.19% for CTX + FOS. Thus, it seemed that CTX + FOS was not more active than FOS alone. In another series of four rabbits per group, the bactericidal effect was followed at T0, T6, T12, T24 and T48 after treatment (two doses with a six-hour with a six-hour interval). With CTX, a variable drop in bacterial count from one rabbit to the other occurred during the first 12 h, and then a bacteriostasis followed. With FOS, a quick bactericidal effect was observed during the first 12 h, becoming slower during the following 36 h (0.03% of bacteria surviving at the 48th hour). With CTX and FOS in combination, a quick bactericidal effect was achieved, remaining steady over a 48-hour period (0.001% of bacteria surviving at the 48th hour).

Topics: Aged; Animals; Cefotaxime; Drug Therapy, Combination; Fosfomycin; Humans; Meningitis; Methicillin; Penicillin Resistance; Rabbits; Staphylococcal Infections; Staphylococcus aureus

Even today antibiotic therapy of postoperative or posttraumatic meningitis remains a problem. In patients in a neurosurgical intensive care unit, nosocomial microorganisms with high resistance are mainly found. There are no antibiotics available which have simultaneously a good efficacy on the higher resistant nosocomial microorganisms and a good penetration through the blood-brain or blood-cerebrospinal fluid barrier. We analysed the cerebrospinal fluid (CSF) penetration of fosfomycin carrying out the investigations in patients in whom a CSF drainage was required for a neurosurgical indication. The blood-brain barrier was considered to be largely intact (total CSF protein and cell counts with in the normal range). Five or 10 g fosfomycin were administered to adults in 30 min infusions. After administration of 5 g, the CSF concentration formed a plateau between 8.6 and 9.9 micrograms/ml 3 to 6 h after the infusion. Increasing the dose infused (10 g) markedly shortened the latency period between reaching a sufficient concentration of fosfomycin in the CSF. With repeated doses of fosfomycin (3 X 5 g/day) the concentration in the CSF did not fall below the therapeutic level. Even in the presence of an intact blood-brain barrier, fosfomycin in our investigation showed a satisfactory penetration into the CSF. This is attributable to the favourable physicochemical state of fosfomycin (relative molecular mass 182).

Topics: Adolescent; Adult; Anti-Bacterial Agents; Blood-Brain Barrier; Fosfomycin; Humans; Injections, Intravenous; Kinetics; Meningitis; Middle Aged; Time Factors

A case of post-traumatic meningitis with otorrhea due to Staphylococcus aureus was successfully treated with a cefotaxim-fosfomycin (CTX-FOS) combination. Serial samples of CSF leaking from the ear showed that maximal concentrations of CTX and FOS, 3.24 mg/l and 19.10 mg/l respectively, occurred one hour after the infusion of both antibiotics was terminated. For desacetyl-cefotaxim (D-CTX), maximal concentration (1.24 mg/l) occurred two hours later. These findings suggest that lumber puncture to control maximal penetration of CTX and FOS into CSF should be done one hour after infusion of both antibiotics.

Topics: Adult; Anti-Bacterial Agents; Cefotaxime; Cerebrospinal Fluid Otorrhea; Drug Resistance, Microbial; Fosfomycin; Humans; Male; Meningitis; Staphylococcal Infections

Cerebrospinal fluid levels of fosfomycin were measured in 10 patients with bacterial meningitis. Fosfomycin 200 mg/kg/day was administered in three 4-hour intravenous infusions. The antibiotic was associated with amoxicillin in 9 patients and with cefotaxime in one. Cerebrospinal fluid was obtained on the 2nd and 5th days of treatment, 2 hours after the end of the infusion. The mean CSF fosfomycin levels were 31 mg/l on the 2nd day and 37.2 mg/l on the 5th day. These levels were higher than the MIC 90 for most bacteria encountered in meningitis. Fosfomycin could be used to treat some cases of bacterial meningitis, but always in association with another antibiotic.

Topics: Adult; Anti-Bacterial Agents; Female; Fosfomycin; Humans; Male; Meningitis

Topics: Aged; Anti-Bacterial Agents; Cefotaxime; Drug Resistance, Microbial; Drug Therapy, Combination; Fosfomycin; Humans; Male; Meningitis; Staphylococcal Infections

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Cerebral Ventricles; Child; Fosfomycin; Humans; Male; Meningitis; Middle Aged; Staphylococcal Infections

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

A comparative study was made of the penetration of fosfomycin, penicillin G, ampicillin and chloramphenicol into the cerebrospinal fluid of patients with meningitis treated with combinations of fosfomycin and one of the other three antibiotics. Minimal inhibitory concentrations and in vitro interaction of these antibiotics against Streptococcus pneumoniae and Neisseria meningitidis strains were determined. 90-96.5% of these strains were sensitive to penicillin G, 95-96.5% to ampicillin, 85-100% to chloramphenicol and 90-100% to fosfomycin. Fosfomycin shows a more marked synergism with penicillin G or ampicillin than with chloramphenicol against both bacterial species. The percentages of penetration into the cerebrospinal fluid were: chloramphenicol, 32%; fosfomycin, 25.7%; ampicillin, 15.9%, and penicillin G, 7.9%. The clinical results show that the combination of fosfomycin + penicillin G or fosfomycin + ampicillin can be an alternative in the treatment of meningitis produced by moderately susceptible strains of S. pneumoniae and N. meningitidis to penicillin G and ampicillin.

Topics: Aged; Anti-Bacterial Agents; Child, Preschool; Drug Interactions; Female; Fosfomycin; Humans; Infant; Male; Meningitis; Meningitis, Meningococcal; Meningitis, Pneumococcal; Middle Aged; Neisseria meningitidis; Streptococcus pneumoniae

Topics: Abscess; Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Child; Drug Evaluation; Enteritis; Female; Fosfomycin; Humans; Male; Meningitis; Middle Aged; Respiratory Tract Infections; Urinary Tract Infections

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

In order to determine the liquor concentration of fosfomycin, we chose 27 patients who were suffering from meningitis with different etiology. According to route, type of administration and doses employed, we classified the patients into five groups. Blood samples were taken from the patients 1 h after concluding the administration of the antibiotic and 2 h after the CSF sample. The concentration of fosfomycin in the serum and the CSF were then determined in the laboratory. In order to evaluate the results we divided our cases into three groups according to the state of their meningeal inflammation. In the first group of patients with active meningitis, we obtained an average concentration of fosfomycin in the serum of 65.20 mug/ml and in the CSF of 10.88 mug/ml. In the second group of patients with meningitis in the remission stage, the concentration of fosfomycin in the serum was 83.58 mug/ml and in the CSF it was 9.63 mug/ml. In the third group of patients with their meningitis cured, the concentration of fosfomycin in the serum was 66.45 mug/ml and in the CSF it was 4.95 mug/ml. On the basis of the concentrations obtained and with regard to the sensitivity in vitro, we concluded that fosfomycin can be useful in the treatment of meningitis caused by Pneumococcus, Staphylococcus, E. coli and other gram-negative bacilli.

Topics: Administration, Oral; Adult; Anti-Bacterial Agents; Fosfomycin; Humans; Injections, Intramuscular; Injections, Intravenous; Meningitis; Time Factors

This report deals with the results of a study that was made on the passage of fosfomycin into the CSF in 22 children with meningitis (11 parotideal meningitis and 11 meningococcal meningitis). The plasma and liquor levels of fosfomycin were determined in the acute phase of the illness and after the normalization of the CSF, with the object of studying the passage of the antibiotic through the blood-brain barrier in the presence and absence of meningeal inflammation. A greater permeability of the meninges was found to exist when they were in an inflammatory state and there seems to be a certain accumulative effect in the CSF when the fosfomycin is administered by intravenous perfusion. The concentrations that were obtained in the CSF were not high enough to justify the exclusive use of fosfomycin in the treatment of meningitis. Nevertheless, considering its wide antibacterial spectrum, its MIC against different microbial species and its lack of toxicity, we believe that fosfomycin can be of use when associated with other antibiotics in the treatment of meningitis caused by S. aureus, D. pneumoniae, H. influenzae, E. coli, P. mirabilis and S. marcescens.

Topics: Acute Disease; Anti-Bacterial Agents; Child; Child, Preschool; Fosfomycin; Humans; Infant; Injections, Intramuscular; Injections, Intravenous; Meningitis; Time Factors