trimethoprim--sulfamethoxazole-drug-combination and Meningitis

17-year-old man had been involved in a traffic accident. He underwent a bilateral craniotomy with artificial dura mater to remove bilateral acute subdural hematomas. Seven months later, a right cranioplasty was performed using frozen auto-bone, and he developed extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae meningitis and an epidural abscess. Since his general status was poor, we could not remove the foreign body (artificial dura mater). He was successfully treated with meropenem and chronic suppression with oral trimethoprim-sulfamethoxazole. By describing this case and the results of a review of the pertinent literature, we discuss the importance of ESBL-producing Klebsiella pneumoniae meningitis in posttraumatic/postoperative patients.

Topics: Adolescent; Anti-Bacterial Agents; beta-Lactamases; Craniotomy; Drug Therapy, Combination; Epidural Abscess; Hematoma, Subdural, Acute; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meningitis; Meropenem; Postoperative Period; Thienamycins; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Listeria monocytogenes has become a major pathogen in foodborne illness. It most often affects patients who are pregnant, at the extremes of life, or immunocompromised in some way. A variety of clinical manifestations are possible, but bacteremia and meningitis are most common. This article reviews the epidemiology, microbiology, populations at risk, clinical manifestations, treatment, and prevention of listeriosis.

Topics: Adolescent; Adult; Age Distribution; Aged; Ampicillin; Bacteremia; Child; Child, Preschool; Endocarditis; Erythromycin; Female; Foodborne Diseases; Gastroenteritis; Humans; Incidence; Infant; Infant, Newborn; Listeria monocytogenes; Listeriosis; Male; Meningitis; Middle Aged; Pregnancy; Pregnancy Complications, Infectious; Survival Rate; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

Three patients with antibiotic induced meningitis, one following penicillin with seven episodes, are reported on--the first well documented description of penicillin induced meningitis. In this patient episodes of headache and nuchal rigidity appeared with and without CSF pleocytosis. Two patients had a total of five episodes of antibiotic induced meningitis after trimethoprim-sulphamethoxazole (co-trimoxazole) administration. The features common to all three patients were myalgia, confusion and low CSF glucose. CSF analysis was not a reliable method to differentiate antibiotic induced meningitis from partially treated bacterial meningitis.

Topics: Adolescent; Aged; Aged, 80 and over; Cerebrospinal Fluid; Confusion; Diagnosis, Differential; Female; Glucose; Headache; Humans; Male; Meningitis; Muscle Rigidity; Neck Muscles; Penicillins; Recurrence; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Anti-Infective Agents; Drug Combinations; Female; Humans; Meningitis; Meningitis, Aseptic; Middle Aged; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

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).

Topics: Aminoglycosides; Anti-Bacterial Agents; Anti-Infective Agents; Bacterial Infections; Cephalosporins; Chloramphenicol; Drug Combinations; Drug Therapy, Combination; Humans; Kinetics; Meningitis; Penicillins; Sulfamethoxazole; Sulfonamides; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

Topics: Aminoglycosides; Ampicillin; Anti-Bacterial Agents; Bacterial Infections; Blood-Brain Barrier; Cephalosporins; Chloramphenicol; Drug Combinations; Humans; Meningitis; Meningitis, Haemophilus; Meningitis, Meningococcal; Meningitis, Pneumococcal; Penicillins; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

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.

Topics: Adolescent; Adult; Animals; Bacteria; Child, Preschool; Drug Combinations; Enterobacteriaceae Infections; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Infant; Infant, Newborn; Kinetics; Male; Meningitis; Microbial Sensitivity Tests; Middle Aged; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Effective therapy for aerobic gram-negative bacillary meningitis is limited by antibiotic resistance among many pathogens and by poor diffusion of some antibiotics into the subarachnoid space. The host response to suppurative meningitis caused by all encapsulated bacteria is impaired by a deficiency of complement and opsonic activity in infected spinal fluid; consequently, therapy with bactericidal antibiotics is preferred. Chloramphenicol diffuses well into cerebrospinal fluid, but is bacteristatic against enteric gram-negative bacilli. Although aminoglycosides are bactericidal, their use requires daily intralumbar or intraventricular injections. Newer cephalosporin compounds, moxalactam and cefotaxime, are bactericidal at very low concentrations and diffuse well from serum to infected spinal fluid. Clinical trials with moxalactam suggest that it is the most effective regimen for enteric gram-negative bacillary meningitis in adults; Pseudomonas aeruginosa and acinetobacter meningitis are most susceptible to a combination of intravenous ticarcillin and aminoglycoside, plus intrathecal aminoglycoside.

Topics: Adult; Aged; Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Cephalosporins; Chloramphenicol; Drug Combinations; Humans; Meningitis; Penicillins; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Post-neurosurgical infection is a serious complication that occurs in approx. 4% of all patients undergoing neurosurgical procedures and is associated with high morbidity and mortality rates and prolonged length of intensive care unit (ICU) stay. Coagulase-negative staphylococci (CoNS), especially methicillin-resistant Staphylococcus epidermidis (MRSE), are the most frequent pathogens involved in CNS post-neurosurgical meningitis. Treatment is challenging especially in patients with meningitis due to multidrug- resistant (MDR) CONS. Herein, we report a unique case of post-neurosurgical meningitis due to MRSE resistant to linezolid (a molecular analysis revealed the presence of the mutation G2576T on domain V of the 23S rRNA gene) and with reduced susceptibility to glycopeptides, successfully treated with a combination of daptomycin at 10 mg/kg daily plus trimethoprim/sulfamethoxazole (TMP/SMX). This antibiotic combination showed an indifferent interaction in in vitro studies. Daptomycin serum and cerebrospinal fluid (CSF) concentrations, determined through blood and CSF samples drawn just prior to and 4 h after the third dose, were 18.9-0.78 and 51.65-3.1 mg/L, respectively. These values allowed us to approximate a 5-6% penetration rate of the drug through an inflamed blood-brain barrier. In conclusion, although further studies are needed, combination of high-dose daptomycin plus TMP/SMX is a reasonable option for treatment of meningitis caused by multidrug-resistant S. epidermidis.

Topics: Acetamides; Anti-Bacterial Agents; Blood-Brain Barrier; Daptomycin; Female; Glycopeptides; Humans; Linezolid; Meningitis; Methicillin Resistance; Microbial Sensitivity Tests; Middle Aged; Oxazolidinones; Prosthesis-Related Infections; Staphylococcus epidermidis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

No data on whether brucellar meningitis or meningoencephalitis can be treated with oral antibiotics or whether an intravenous extended-spectrum cephalosporin, namely, ceftriaxone, which does not accumulate in phagocytes, should be added to the regimen exist in the literature. The aim of a study conducted in Istanbul, Turkey, was to compare the efficacy and tolerability of ceftriaxone-based antibiotic treatment regimens with those of an oral treatment protocol in patients with these conditions. This retrospective study enrolled 215 adult patients in 28 health care institutions from four different countries. The first protocol (P1) comprised ceftriaxone, rifampin, and doxycycline. The second protocol (P2) consisted of trimethoprim-sulfamethoxazole, rifampin, and doxycycline. In the third protocol (P3), the patients started with P1 and transferred to P2 when ceftriaxone was stopped. The treatment period was shorter with the regimens which included ceftriaxone (4.40 ± 2.47 months in P1, 6.52 ± 4.15 months in P2, and 5.18 ± 2.27 months in P3) (P = 0.002). In seven patients, therapy was modified due to antibiotic side effects. When these cases were excluded, therapeutic failure did not differ significantly between ceftriaxone-based regimens (n = 5/166, 3.0%) and the oral therapy (n = 4/42, 9.5%) (P = 0.084). The efficacy of the ceftriaxone-based regimens was found to be better (n = 6/166 [3.6%] versus n = 6/42 [14.3%]; P = 0.017) when a composite negative outcome (CNO; relapse plus therapeutic failure) was considered. Accordingly, CNO was greatest in P2 (14.3%, n = 6/42) compared to P1 (2.6%, n = 3/117) and P3 (6.1%, n = 3/49) (P = 0.020). Seemingly, ceftriaxone-based regimens are more successful and require shorter therapy than the oral treatment protocol.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anti-Bacterial Agents; Brucella; Brucellosis; Ceftriaxone; Doxycycline; Drug Therapy, Combination; Female; Humans; Injections, Intravenous; Male; Meningitis; Meningoencephalitis; Middle Aged; Recurrence; Retrospective Studies; Rifampin; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination; Turkey

Neurobrucellosis is an uncommon complication of pediatric brucellosis. Acute meningitis and encephalitis are the most common clinical manifestations, however symptoms may be protean and diagnosis requires a high index of suspicion in patients from endemic areas. Diagnosis is often based on neurological symptoms, serology, and suggestive brain imaging because cerebrospinal fluid culture yields are low. Two cases of pediatric neurobrucellosis with unusual clinical and radiologic findings are presented.

Topics: Adolescent; Anti-Bacterial Agents; Brucellosis; Child; Doxycycline; Drug Therapy, Combination; Encephalitis; Female; Gentamicins; Humans; Incidence; Israel; Meningitis; Neuroimaging; Rifampin; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Elizabethkingia meningoseptica is a recognised cause of meningitis in premature neonates and severe infections in immunocompromised adults; multi-drug resistance is a major issue. A premature infant developed sepsis, meningitis and hydrocephalus owing to E. meningoseptica and was treated successfully with trimethoprim-sulfamethoxazole (TMP-SMZ) for 3 weeks. A ventriculoperitoneal shunt was required for hydrocephalus. This is the youngest patient with meningitis caused by E. meningoseptica to have responded to TMP-SMZ.

Topics: Anti-Bacterial Agents; Brain; Drug Resistance, Multiple, Bacterial; Female; Flavobacteriaceae; Flavobacteriaceae Infections; Humans; Hydrocephalus; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Meningitis; Sepsis; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination; Ventriculoperitoneal Shunt

Nocardiosis is a life-threatening infection that affects the lungs, skin, and central nervous system, particularly in immune-compromised patients. We report a case of disseminated nocardiosis with pneumonia, brain abscesses, meningitis, and thyroiditis, for an individual with recent steroid therapy. Recovery was uneventful with a 4-month course of sulfamethoxazole-trimethoprim.

Topics: Aged; Brain Abscess; Female; Humans; Meningitis; Nocardia; Nocardia Infections; Pneumonia; Thyroid Diseases; Thyroiditis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Bacterial Agents; Bacteremia; Blood; Cerebrospinal Fluid; Female; Flavobacteriaceae; Flavobacteriaceae Infections; Humans; Meningitis; Microscopy; Middle Aged; Rifampin; Stem Cell Transplantation; Transplantation; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Acanthamoeba was implicated as the causative agent of chronic meningitis in three apparently immunocompetent children. Diagnosis was established by cerebrospinal fluid wet mount examination and culture. Two children improved rapidly with combination oral therapy composed of trimethoprim-sulfamethoxazole, rifampin and ketoconazole.

Topics: Acanthamoeba; Administration, Oral; Amebiasis; Animals; Anti-Infective Agents; Antifungal Agents; Child; Child, Preschool; Chronic Disease; Drug Therapy, Combination; Enzyme Inhibitors; Female; Humans; Ketoconazole; Magnetic Resonance Imaging; Male; Meningitis; Rifampin; Trimethoprim, Sulfamethoxazole Drug Combination

Drug-induced meningitis is rarely included in the differential diagnosis of aseptic (usually recurrent) meningitis. A 74-year-old man who suffered from recurrent aseptic meningitis following re-exposures to trimethoprim-sulphamethoxazole (Resprim) is presented. The clinical and laboratory findings resembled those found in bacterial meningitis, excluding normal glycorrachia. Extensive microbiological, serologic and imaging studies did not disclose any relevant findings. All symptoms and signs resolved rapidly following drug withdrawal, and findings on follow-up lumbar puncture were normal.

Topics: Aged; Anti-Infective Agents; Diagnosis, Differential; Humans; Male; Meningitis; Trimethoprim, Sulfamethoxazole Drug Combination

Meningitis is usually produced by an infectious agent, but there are multiple noninfectious causes. Medications may produce both acute and recurrent meningitis. We present a patient with 3 episodes of aseptic meningitis due to trimethoprim-sulfamethoxazole, and then review the topic of drug-induced meningitis.

Topics: Adult; Female; Humans; Meningitis; Meningitis, Aseptic; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Cefotaxime; Female; Humans; Meningitis; Meningitis, Aseptic; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Anti-Bacterial Agents; Bacterial Infections; Child; Drug Combinations; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Meningitis; Sepsis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Vidarabine; Virus Diseases

Infection with Brucella melitensis is endemic in Saudi Arabia but involvement of the central nervous system (CNS) is rare. We report on three patients with acute brucella meningitis, all of whom had a history of exposure to a possible source of infection. Diagnosis was confirmed by isolation of Brucella species from blood cultures. Examination of cerebrospinal fluid revealed lymphocytic pleocytosis with a high concentration of protein and low concentration of glucose. The patients were treated by combinations of co-trimoxazole, doxycycline or rifampicin. All responded well without recurrences. A combination of two of the three drugs was effective in treating brucellosis of the CNS when given for a period of 6-8 weeks.

Topics: Adult; Brucellosis; Doxycycline; Drug Combinations; Female; Humans; Male; Meningitis; Middle Aged; Rifampin; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Ampicillin; Anti-Bacterial Agents; Chloramphenicol; Drug Combinations; Humans; Infant; Meningitis; Middle Aged; Salmonella Infections; Sepsis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Co-trimoxazole was compared with nafcillin against Staphylococcus aureus in vitro and in the therapy of experimental Staph. aureus meningitis in rabbits. Co-trimoxazole (trimethoprim:sulphamethoxazole in a 1:20 ratio) was synergistic against 22/24 strains of Staph. aureus in vitro. The MBC90 of co-trimoxazole and nafcillin were 0.156-3.12 mg/l and 0.25 mg/l, respectively, concentrations below those achievable in purulent cerebrospinal fluid. The rate of bacterial killing (Staph. aureus) by co-trimoxazole and nafcillin were similar in both broth and pooled CSF in vitro. However, the MBC increased and the rate of bactericidal activity of both agents declined when tested in CSF at a higher inoculum (10(7) cfu/ml). During continuous intravenous infusion therapy of a reproducible, uniformly fatal (if untreated) model of experimental Staph. aureus meningitis, serum concentrations of all agents closely approximated those found in humans receiving standard parenteral regimens. The mean percent penetration into CSF ([CSF]/[serum] X 100) was 2.9, 35.6 and 27.1% for nafcillin, trimethoprim and sulphamethoxazole, respectively. Although both nafcillin and co-trimoxazole therapy reduced CSF Staph. aureus concentrations significantly more rapidly (P less than 0.001) when compared to untreated controls, the bactericidal rate was modest. The CSF was rendered sterile in 0/64 animals treated with either regimen for 8 h. Nafcillin was more rapidly bactericidal in vivo (P less than 0.03) than co-trimoxazole in this model. Caution is advised in the use of co-trimoxazole for infections of the central nervous system caused by Staph. aureus.

Topics: Animals; Anti-Bacterial Agents; Drug Combinations; Meningitis; Microbial Sensitivity Tests; Nafcillin; Rabbits; Staphylococcal Infections; Staphylococcus aureus; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

We present a case of a 45-yr-old black male who developed both meningitis and osteomyelitis due to Yersinia enterocolitica. This particular case was remarkable because the patient made a full recovery without long-term sequelae after therapy with IV chloramphenicol followed by oral trimethoprim-sulfamethoxazole.

Topics: Chloramphenicol; Drug Combinations; Humans; Male; Meningitis; Middle Aged; Osteomyelitis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Yersinia enterocolitica; Yersinia Infections

We report 5 patients with repeated episodes of meningitis related to intake of trimethoprim containing compounds. On at least one occasion the patients received pure trimethoprim prior to reaction. Autoimmune disease was established in 3 of the patients. A close temporal relationship between drug intake and reaction was noted: symptoms appeared often within minutes. No evidence of infections was found. Lumbar puncture after recovery revealed normal values in 2 patients. This aseptic meningitis is most likely an adverse drug reaction and associated with trimethoprim intake. The reaction is infrequently reported in relation to drug sales but its incidence has probably been underestimated.

Topics: Adolescent; Adult; Aged; Anti-Infective Agents, Urinary; Autoimmune Diseases; Drug Combinations; Female; Humans; Meningitis; Meningitis, Aseptic; Sulfamethoxazole; Time Factors; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Topics: Adolescent; Adult; Aminoglycosides; Anti-Bacterial Agents; Anti-Infective Agents; Cephalosporins; Child; Child, Preschool; Chloramphenicol; Drug Combinations; Fever; Humans; Infant; Infant, Newborn; Meningitis; Middle Aged; Penicillins; Sulfamethoxazole; Tetracycline; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Anti-Infective Agents, Urinary; Drug Combinations; Female; Humans; Meningitis; Meningitis, Aseptic; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Acute monosymptomatic aseptic meningitis was observed in a 4 year old male patient. Toxoplasma gondii tachyzoites were detected in Giemsa-stained smears prepared from the CSF. Inoculation of mice gave the same result. The patient was cured after the application of pyrimethamine and sulpha drugs. On basis of the smears, the serological results and data in the literature, a direct infection through the nasal cavity has been assumed.

Topics: Acute Disease; Child, Preschool; Drug Combinations; Folic Acid; Humans; Male; Meningitis; Meningitis, Aseptic; Pyrimethamine; Staining and Labeling; Sulfamethoxazole; Toxoplasmosis; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Drug Combinations; Humans; Meningitis; Meningitis, Aseptic; Sjogren's Syndrome; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

The incidence of gram-negative bacillary meningitis has increased significantly in the past two decades. Approximately two thirds of all reported cases have occurred after neurosurgical procedures. With the development of the newer cephalosporins, the overall mortality rate has decreased from 40 to 80 per cent to 10 to 20 per cent.

Topics: Aminoglycosides; Anti-Bacterial Agents; Cephalosporins; Chloramphenicol; Drug Combinations; Gram-Negative Bacteria; Humans; Meningitis; Penicillins; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Child, Preschool; Drug Combinations; Drug Resistance, Microbial; Escherichia coli Infections; Humans; Leukemia, Lymphoid; Male; Meningitis; Sepsis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Drug Combinations; Enterobacteriaceae Infections; Gram-Negative Bacteria; Humans; Male; Meningitis; Middle Aged; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents, Urinary; Drug Combinations; Female; Humans; Meningitis; Middle Aged; Recurrence; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

We evaluated the activity of trimethoprim/sulfamethoxazole (TMP/SMZ) against a K1 Escherichia coli strain. Minimal inhibitory and bactericidal concentrations were 0.06/1.14 and 0.25/4.75 micrograms/ml, respectively. In vivo studies using an infant rat model of bacteremia and meningitis revealed that TMP/SMZ penetrated well into the cerebrospinal fluid (CSF) and that 37% of serum levels were achieved. The efficacy of TMP/SMZ was compared with that of ampicillin, chloramphenicol, cefotaxime and lamoxactam. Bacterial clearance from blood and CSF was significantly greater with TMP/SMZ than with ampicillin or chloramphenicol and mortality was significantly less than with chloramphenicol (p less than 0.01). However, 3 of 21 (14%) and 2 of 8 animals (25%) still had positive blood and CSF cultures after 3 days of treatment with TMP/SMZ. None of the survivors in the cefotaxime and lamoxactam groups were bacteremic after 1 day of therapy. Furthermore, 5 of 13 animals (38%) treated with TMP/SMZ developed meningitis during therapy, in contrast with none in the cefotaxime and lamoxactam groups. These findings indicate that although the activity of TMP/SMZ is bactericidal in vitro and in vivo against E. coli, TMP/SMZ may not provide optimal therapy for gram-negative bacillary meningitis in this model.

Topics: Animals; Colony-Forming Units Assay; Drug Combinations; Escherichia coli Infections; Meningitis; Rats; Sepsis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Administration, Oral; Adult; Aged; Cerebral Hemorrhage; Child; Drug Combinations; Female; Humans; Infant; Male; Meningitis; Middle Aged; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

There are increasing reports of citrobacter central nervous system infections in neonates. These organisms cause brain abcesses in a high percentage of patients. They may be resistant to commonly used antibiotics. We report a term male infant with underlying meningo-myelocoele and hydrocephalus in whom Citrobacter diversus meningitis and ventriculitis developed. Initial antibiotic therapy including intraventricular amikacin failed to sterilize the ventricles or alter a deteriorating clinical course. Adding intravenous trimethoprim-sulfamethoxazole to the therapeutic regimen resulted in reversal of a progressively worsening condition and eventual recovery. Trimethoprim-sulfamethoxazole should be considered as a potentially useful alternative antibiotic for susceptible central nervous system infections.

Topics: Amikacin; Cerebral Ventricles; Citrobacter; Drug Combinations; Encephalitis; Enterobacteriaceae Infections; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Meningitis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Drug Combinations; Drug Hypersensitivity; Female; Humans; Meningitis; Meningitis, Aseptic; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acinetobacter Infections; Cross Infection; Drug Combinations; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Meningitis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Normal doses of co-trimoxazole (two ampoules or two tablets twice a day) gave low cerebrospinal fluid concentrations of trimethoprim and sulphamethoxazole in neurosurgical patients. For two years, four ampoules of co-trimoxazole twice a day, followed by four tablets twice a day, which were administered to neurosurgical patients and to patients admitted to hospital with skull fractures, produced no toxicity and this regimen has not been associated with postoperative meningitis. After the high-dose regimen in patients with uninflamed meninges, trimethoprim concentrations in the cerebrospinal fluid ranged from 2.6 mumol/L to 12.4 mumol/L (0.75 mg/L to 3.6 mg/L), and in the serum from 9.6 mumol/L to 42.7 mumol/L (2.8 mg/L to 12.4 mg/L). However, the bacteriostatic and bactericidal activities of the spinal fluids and sera were very variable, some with high concentrations appearing to have negligible antibacterial activity in vitro. We have treated a few patients with serious infections with dosages of 12 ampoules or 12 tablets twice a day with successful results. Studies of serum folate, 5-methyltetrahydrofolate and granulocyte dihydrofolate reductase levels showed no toxic effects from the high-dose regimen.

Topics: Adolescent; Adult; Drug Combinations; Female; Humans; Injections, Intravenous; Male; Meninges; Meningitis; Microbial Sensitivity Tests; Middle Aged; Neurosurgery; Sulfamethoxazole; Time Factors; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination