Treatment Of Gram-negative Bacillary Meningitis Research Articles

Post ventriculoperitoneal shunting S. Maltophilia Meningitis

Background: Leptomeningeal inflammation caused by S. Maltophilia is rare. It is inextricably linked with prior antimicrobial therapy, prolonged ICU stays and antecedent neurosurgical intervention. Case description: We describe a case of a 5-year-old male child with posterior fossa medulloblastoma with obstructive hydrocephalus who underwent ventriculoperitoneal shunt followed by suboccipital midline craniotomy and later presented with S. Maltophilia meningitis. Conclusion: The overall mortality in the cases reviewed was 17 per cent. Inherent resistance to a wide array of antimicrobial agents with a simultaneously increasing number of cases poses a therapeutic challenge. Trimethoprim/sulfamethoxazole is recommended as empirical and as a definitive treatment in patients with S. Maltophilia infection. The optimal duration of therapy for S. Maltophilia meningitis is similar to the treatment of gram-negative bacillary meningitis, which is usually 2 weeks after the culture has been negative.

Adjunctive dexamethasone treatment in acute bacterial meningitis

The initiation of antibiotic treatment on suspicion of bacterial meningitis is important, but it is not enough to improve the prognosis for patients, especially those with pneumococcal meningitis. The mortality and morbidity of pneumococcal meningitis are still devastating, and results of a recent randomised trial have shown evidence in favour of dexamethasone treatment given before or with the first antibiotic dose. Adjuvant dexamethasone is unequivocally recommended in children and adults with haemophilus meningitis or pneumococcal meningitis. The benefit of adjunctive dexamethasone is likely to be greatest in patients who are otherwise healthy and present early with acute bacterial meningitis. Dexamethasone is not currently recommended for the treatment of gram-negative bacillary meningitis and neonatal meningitis. Dexamethasone, before or with the first dose of antibiotic, is likely to be one of the most significant practice changes that will benefit many adults and children with common types of acute bacterial meningitis and has been of proven value in the developed world.

Aztreonam in the Treatment of Gram-Negative Bacterial Meningitis

Aztreonam was administered to 122 patients with presumptive or confirmed gram-negative bacillary meningitis in an open, multinational study. The antibiotic was administered at a dosage of 1-2 g to adults, 50 mg/kg to children greater than 2 years old, and 30 mg/kg to infants three or four times daily. Seventy-seven patients had microbiologically confirmed gram-negative meningitis due to an aztreonam-susceptible organism and received aztreonam for at least 48 hours. Haemophilus influenzae was the most frequently recovered pathogen (40 patients), followed by Enterobacteriaceae (16 patients), Neisseria meningitidis (15 patients), and Pseudomonas species (six patients). All but four patients were microbiologically cured. Microbiologic failure was associated with either a persistent intracerebral abscess (one patient) or a foreshortened course of therapy before microbiologic reevaluation and death (at 48 hours, 48 hours, and 72 hours after initiation of treatment, respectively). These data suggest that aztreonam is effective in the treatment of gram-negative bacillary meningitis caused by susceptible organisms.

Bacterial Meningitis: Recent Advances in Pathophysiology and Treatment

To review recent advances in the understanding of pathogenic and pathophysiologic mechanisms underlying bacterial meningitis that may lead to the development of adjunctive strategies for treating this disorder. Studies published from 1975 to 1989 were identified using Index Medicus and by reviewing the bibliographies of identified articles. We reviewed the experimental and human studies evaluating pathogenesis, pathophysiology, and antimicrobial treatment of bacterial meningitis, as well as those reviews that have contributed to our understanding of meningitis. We evaluated the data on the pathogenesis, pathophysiology, and treatment of bacterial meningitis and considered in depth the information from animal models that may have potentially important applications in the treatment of human disease. Penicillin and ampicillin remain the drugs of choice for meningitis caused by Streptococcus pneumoniae and Neisseria meningitidis. The third-generation cephalosporins have revolutionized the treatment of gram-negative bacillary meningitis; one such agent, ceftazidime, is also useful for treating Pseudomonas aeruginosa meningitis. Modification of subarachnoid space inflammation by anti-inflammatory agents may lessen many of the pathophysiologic consequences of bacterial meningitis. A recent study of adjunctive dexamethasone therapy in infants and children with bacterial meningitis showed that the incidence of long-term neurologic sequelae was lower in the corticosteroid group. Future therapy for bacterial meningitis will use recent developments in the understanding of pathogenic and pathophysiologic mechanisms underlying this disease. Additional studies using monoclonal antibodies against specific virulence factors and investigations into the production of inflammatory cytokines in response to bacterial cell products may lead to additional treatments that decrease the high morbidity and mortality in patients with bacterial meningitis.

Brief report: Ciprofloxacin in the treatment of gram-negative bacillary meningitis

Gram-negative bacillary meningitis (typically caused by E. coli, K. pneumoniae, P. aeruginosa, A. calcoaceticus, and others) has been associated with head trauma, neurosurgical operations, pathologic anastomosis with nasal cavity, and CSF rhinorrhea, as well as with impaired host defenses. Intravenous ciprofloxacin was given to 20 patients with gram-negative bacillary meningitis. The dose of ciprofloxacin was 200 mg by intravenous infusion, over 30 minutes, every 12 hours for 10 days. Two patients also received intravenous cefotaxime and penicillin G. All patients were monitored daily. Of 20 patients, 18 had cure and therapy failed in two. Because relatively low concentrations of ciprofloxacin are achieved in the CSF, the drug should be used in the treatment of gram-negative bacillary meningitis only if the MICs of the causative pathogen and the ciprofloxacin concentration in CSF can be followed. A randomized, controlled study is needed to compare the efficacy of intravenous ciprofloxacin with standard antibiotic therapy in the treatment of this disease.

Bacterial meningitis. Rational selection and use of antibacterial drugs.

Bacterial meningitis is a continuing challenge. This applies especially to infections in the neonate and the elderly, and to those which are hospital acquired. Factors which maintain the high morbidity and significant mortality from this disease include microbial virulence, a limited host response to infection within the cerebrospinal fluid (CSF), where phagocyte function is often impaired and complement and opsonic antibody activity are deficient, as well as delays in diagnosis and treatment. Added to these adverse factors is the pharmacokinetic hurdle of the 'blood-brain barrier', which limits drug concentrations achievable within the CSF. Inflammatory changes certainly improve the penetration of many agents, especially the penicillins and cephalosporins, but it must be remembered that with resolution of inflammation, achievable concentrations decline. Hence, the necessity for continuing parenteral administration of antibiotics throughout the treatment period. Although penicillin G (benzylpenicillin) remains the drug of choice for both pneumococcal and meningococcal infections, increasing resistance to ampicillin among Haemophilus influenzae has lead to greater reliance on alternative agents. Chloramphenicol is widely used, yet is potentially toxic, so that therapy with cefuroxime and the newer cephalosporins has been increasingly advocated. The advent of these potent, broad spectrum cephalosporins has induced a reappraisal of the treatment of Gram-negative bacillary meningitis, where ampicillin resistance and poor CSF penetration by the aminoglycosides have contributed to an unsatisfactory impact on outcome. Agents such as cefotaxime and ceftazidime have proved effective, although greater controlled experience is required. Finally, the contagious nature of meningococcal and H. influenzae infections justifies offering chemoprophylaxis to selected contacts, with rifampicin (or minocycline for contacts of patients with meningococcal infections).

Review of Pseudomonas aeruginosa meningitis with special emphasis on treatment with ceftazidime.

Pseudomonas aeruginosa meningitis is a rare disease and the optimal antibiotic therapy for this condition is not well established. Results of therapy using various regimens reported since 1960 are reviewed. Ceftazidime, an investigational cephalosporin with potent antipseudomonal activity, has been used to treat P. aeruginosa meningitis in Europe and North America. The results in 24 patients are analyzed here. Most patients had failed to respond to other regimens before commencing therapy with ceftazidime. Nineteen (79.2%) of these patients were cured, and only three (12.5%) were considered therapeutic failures. Hence, ceftazidime is a useful agent in the treatment of gram-negative bacillary meningitis and may be superior to other cephalosporins on the market for the treatment of pseudomonas meningitis. Since development of resistance is a concern, however, it may be prudent to use a concomitant parenteral aminoglycoside with ceftazidime for the first week in the treatment of P. aeruginosa meningitis.

Bacterial Meningitis in the Elderly-Reply

—Dr Harris focuses on specific clinical characteristics of our older adult population (age, ≥50 years) and reiterates concerns regarding efficacy of third-generation cephalosporins in the treatment of gramnegative bacillary meningitis. 1 It is important to differentiate those patients with microbiologically proved bacterial meningitis from those with presumed bacterial infections treated as such. In the latter group, situations associated with a negative bacterial culture included prior antibiotic treatment, parameningeal focus of infection, and CSF leak due to prior trauma or neurosurgical procedure. While higher mortality correlated with positive microbiologie diagnosis in our series of patients,1 characteristics (eg, preexisting neurologic disease, previous neurologic surgical procedures, change in sensorium at time of presentation, and community onset vs hospital onset) did not differ significantly between these two subgroups (Table 1). The eight patients with aseptic meningitis had no preexisting neurologic disease or neurologic surgical procedures, and all had community-acquired infection. The mean CSF white blood cell

A Study of the Penetration of Temocillin in the Cerebrospinal Fluid1

Temocillin concentrations in serum and cerebrospinal fluid (CSF) samples from 8 patients were assayed by high pressure liquid chromatography. It was possible to determine sequential series of ventricular (CSF) and serum concentrations in 4 adult neurosurgical patients with slight to moderate impairment of blood-CSF barriers, because serial CSF samples were obtained from external ventricular drains. In 4 other patients with meningitis, temocillin was given in addition to the regular treatment schedule and 6 'spot' concentrations of temocillin in lumbar CSF and serum samples were determined. Temocillin CSF concentrations in these subjects seemed to be inadequate for the treatment of Gram-positive bacterial meningitis and only partially valuable for the treatment of Gram-negative bacillary meningitis.

Penetration of aztreonam into cerebrospinal fluid of patients with and without inflamed meninges.

Aztreonam was administered as a single, 2-g intravenous dose to 25 patients with noninflamed meninges and to 9 patients with inflamed meninges. It was well tolerated and was detected in the cerebrospinal fluid at the initial sampling period at 1 h after the end of infusion. Aztreonam levels in the cerebrospinal fluid of patients with inflamed meninges were four times higher than those recorded for the same time period in patients with noninflamed meninges. Aztreonam concentrations in cerebrospinal fluid in the presence of normal and inflamed meninges exceeded the inhibitory and bactericidal concentrations for most gram-negative bacteria. Thus, a multiple-dose treatment regimen with 2-g intravenous doses every 6 h appears to be appropriate for clinical trials of aztreonam for the treatment of gram-negative bacillary meningitis which is caused by susceptible organisms.

Trimethoprim-sulfamethoxazole for bacterial meningitis.

Trimethoprim-sulfamethoxazole has excellent microbiologic activity against most pathogens that produce meningitis; both components of this drug have high penetration into tissues, including the cerebrospinal fluid. Clinical experience shows that trimethoprim-sulfamethoxazole may be beneficial in the treatment of gram-negative bacillary meningitis caused by organisms only moderately susceptible to third-generation cephalosporins (Enterobacter cloacae, Serratia marcescens) or resistant to these antibiotic agents (Pseudomonas cepacia, Acinetobacter). The success of trimethoprim-sulfamethoxazole in the treatment of four patients with Staphylococcus aureus and two patients with Listeria monocytogenes meningitis shows that this drug may also be useful in treating infrequent types of gram-positive meningitis.

Diffusion of metioprim, tetroxoprim and sulphadiazine in the cerebrospinal fluid of dogs with healthy meninges and dogs with experimental meningitis.

The diffusion of metioprim (MTP), tetroxoprim (TXP) and sulphadiazine (SDZ) in cerebrospinal fluid (CSF), following single intravenous doses and continuous infusions, was studied in dogs. The drugs penetrated well into the CSF of animals with and without experimental Staphylococcus aureus meningitis. In dogs with healthy meninges, the CSF bioavailability - expressed as the ratio of CSF/plasma area under the curve 0-5-hour values - following continuous infusion was determined to be 86.7% for MTP, 58.2% for TXP and 38.8% for SDZ. In infected animals, CSF availability following continuous infusion increases slightly to ratios of 96% (MTP), 70% (TXP) and 50% (SDZ). For all drugs, the concentrations reached in CSF were above the minimum inhibition concentrations for the majority of Enterobacteriaceae, indicating their potential value in treatment of gram-negative bacillary meningitis.

Successful treatment of gram-negative bacillary meningitis with moxalactam: Olson DA, Hoeprich PD, Nolan SM, et al Ann Intern Med 95:302–305 Sep 1981

Successful treatment of gram-negative bacillary meningitis with moxalactam: Olson DA, Hoeprich PD, Nolan SM, et al Ann Intern Med 95:302–305 Sep 1981

Relapse of Gram-negative Bacillary Meningitis After Cefotaxime Therapy

CONSIDERABLE enthusiasm has developed regarding the treatment of gram-negative bacillary meningitis with newly developed broad-spectrum, third-generation cephalosporin antibiotics. 1,2 Compared with other agents such as aminoglycosides or previously available cephalosporins, these antibiotics have remarkable activity against the organisms that cause this life-threatening infection. 3 The degree of penetration across the blood-brain barrier is so much greater for third-generation cephalosporins than the previously utilized antibiotics for gram-negative bacillary meningitis that many investigators now suggest that either cefotaxime sodium or moxalactam disodium is the drug of choice for this infection. 1 Since the proved therapy of intraventricular aminoglycoside administration may be associated with serious hazards, 4 the relative safety of cephalosporins is attractive. The relapse rate, however, has not been determined for this therapy with new cephalosporins. We recently gave one of these agents to a patient with gram-negative bacillary meningitis and observed an adequate initial response followed by relapse of infection.

Designing appropriate therapy in the treatment of gram-negative bacillary meningitis

Designing appropriate therapy in the treatment of gram-negative bacillary meningitis

Designing Appropriate Therapy in the Treatment of Gram-Negative Bacillary Meningitis

Gram-negative bacillary meningitis is being diagnosed more frequently, and the introduction of newer beta-lactam antibiotics has contributed significantly to successful therapy. These new agents--became of their ease of administration and relative safety--also allow nonspecialists to treat the disease. There are, however, pitfalls in therapy of infections due to this heterogenous group of organisms. Extremely susceptible organisms, such as Escherichia coli and Klebsiella pneumoniae, most often respond to cephalosporin monotherapy, whereas relatively resistant organisms such as Acinetobacter and some Enterobacter may not. In these cases, combination therapy with an aminoglycoside is warranted. Testing the infecting organism for antibiotic susceptibility at the appropriate inoculum and pH may be useful in predicting therapeutic outcome.

Successful treatment of gram-negative bacillary meningitis with moxalactam

We report a case of Serratia marcescens meningitis that was unresponsive to therapy with ticarcillin plus systemic and intrathecal amikacin. The administration of moxalactam, 12 g/day intravenously, for 4 weeks resulted in eradication of the infection without sequelae. We were able to document therapeutic levels of moxalactam in the cerebrospinal fluid (CSF), and adequate CSF bactericidal activity was obtained. Moxalactam and other third generation cephalosporins may be valuable agents in the management of gram-negative bacillary meningitis. (Neurosurgery 10:762-765, 1982)

Successful Treatment of Gram-Negative Bacillary Meningitis with Moxalactam

Meningitis caused by enteric gram-negative bacilli is relatively uncommon but is very difficult to treat despite susceptibility in vitro to many antimicrobics. A major problem appears to be poor entry of many drugs into the central nervous system. Moxalactam is an investigational cephalosporin that attains concentrations in the cerebrospinal fluid that are 15% to 30% of contemporaneous serum concentrations; moreover, it is quite active against many of the enteric gram-negative bacilli. We used moxalactam to treat meningitis caused by Enterobacter cloacae, Klebsiella pneumoniae, and Escherichia coli in four adults and one child, giving up to 100 mg/kg body weight per day by intravenous injection. The concentrations of moxalactam in serum, lumbar, and ventricular cerebrospinal fluid exceeded the minimal lethal concentrations of all causative bacteria. The patients were cured. In this small series, moxalactam, when administered intravenously as the sole agent of therapy, was effective in the treatment of meningitis caused by susceptible gram-negative bacilli.

Intraventricular use of aminoglycosides in the treatment of gram-negative bacillary meningitis: conflicting views.

Intraventricular use of aminoglycosides in the treatment of gram-negative bacillary meningitis: conflicting views.

Diffusion of a new beta-lactam (LY 127935) into cerebrospinal fluid: Implications for therapy of gram-negative bacillary meningitis

LY 127935, a new oxa beta-lactam with an expanded gram-negative spectrum, was administered intravenously to seven patients, including two patients with documented gram-negative bacillary meningitis. In the patients receiving continuous therapy (2 g intravenously every 8 hours) cerebrospinal fluid trough levels of LY were never less than 6 μg/ml. Peak cerebrospinal fluid levels of LY ranged from 25 to 39 μg/ml and occurred approximately 2.5 hours after the intravenous administration of the drug. Cerebrospinal fluid levels of LY were 19 per cent to greater than 100 per cent of simultaneous serum levels. Cerebrospinal fluid bactericidal activity was 1:4 to 1:256. Intravenous LY, because of its expanded gram-negative spectrum and excellent cerebrospinal fluid penetration, is a potentially useful antibiotic in the treatment of gram-negative bacillary meningitis.