Aseptic meningitis, hepatitis and cholestasis induced by trimethoprim/sulfamethoxazole: a case report.
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ABSTRACT: Background
Drug-induced aseptic meningitis is a rare, but challenging diagnosis, most commonly reported with nonsteoroidal anti-inflammatory drugs (NSAIDs) and antibiotics. Trimethoprim/sulfamethoxazole (TMP/SMX) is a sulfonamide that is widely used in clinical practice for the treatment and prophylaxis of various infections. The most common side effects associated with TMP/SMX are generally mild and self-limited, but serious side effects have been reported, including liver injury and aseptic meningitis.Case presentation
We report a 2,5 year old Dutch girl with both drug-induced aseptic meningitis and drug-induced liver injury while using TMP/SMX prophylaxis. Ursodeoxycholic acid was started because of cholestatic injury. After cessation of TMP/SMX, full convalescence was reached within weeks.Conclusions
This is the first report of a young patient with both aseptic meningitis and drug-induced liver injury caused by TMP/SMX. Drug-induced aseptic meningitis and cholestatic hepatitis constitute a considerable diagnostic challenge to clinicians. In addition to a thorough evaluation for infectious causes, clinicians should be aware of drug-induced aseptic meningitis and cholestatic hepatitis.
SUBMITTER: van Asperdt JAA
PROVIDER: S-EPMC8365906 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectivesTo characterise the risk of admission to hospital for hyperkalaemia in elderly patients treated with trimethoprim-sulfamethoxazole in combination with spironolactone.DesignPopulation based nested case-control study.SettingOntario, Canada, from 1 April 1992 to 1 March 2010.ParticipantsCases were residents of Ontario aged 66 years or above receiving chronic treatment with spironolactone and admitted to hospital with hyperkalaemia within 14 days of receiving a prescription for either trimethoprim-sulfamethoxazole, amoxicillin, norfloxacin, or nitrofurantoin. Up to four controls for each case were identified from the same cohort, matched on age, sex, and presence or absence of chronic kidney disease and diabetes, and required to have received one of the study antibiotics within 14 days before the case's index date.Main outcome measuresOdds ratio for association between admission to hospital with hyperkalaemia and receipt of a study antibiotic in the preceding 14 days, adjusted for conditions and drugs that may influence risk of hyperkalaemia.ResultsDuring the 18 year study period, 6903 admissions for hyperkalaemia were identified, 306 of which occurred within 14 days of antibiotic use. Of these, 248 (81%) cases were matched to 783 controls. 10.8% (17,859/165,754) of spironolactone users received at least one prescription for trimethoprim-sulfamethoxazole. Compared with amoxicillin, prescription of trimethoprim-sulfamethoxazole was associated with a marked increase in the risk of admission to hospital for hyperkalaemia (adjusted odds ratio 12.4, 95% confidence interval 7.1 to 21.6). The population attributable fraction was 59.7%, suggesting that approximately 60% of all cases of hyperkalaemia in older patients taking spironolactone and treated with an antibiotic for a urinary tract infection could be avoided if trimethoprim-sulfamethoxazole was not prescribed. Treatment with nitrofurantoin was also associated with an increase in the risk of hyperkalaemia (adjusted odds ratio 2.4, 1.3 to 4.6), but no such risk was found with norfloxacin (adjusted odds ratio 1.6, 0.8 to 3.4)ConclusionsAmong older patients receiving spironolactone, treatment with trimethoprim-sulfamethoxazole was associated with a major increase in the risk of admission to hospital for hyperkalaemia. This drug combination should be avoided when possible.
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Project description:BACKGROUND:Torque teno virus-induced aseptic meningitis has not been documented, although torque teno virus infections still remain under consideration for etiological agents. This study identified a torque teno virus sequence using next generation sequencing and immunoglobulin M response to the torque teno virus antigen, therefore, that would be a comprehensive diagnosis for torque teno virus infection. CASE PRESENTATION:A 2-month-old Japanese boy was brought to our hospital because he was irritable, drowsy, and lethargic. He was admitted based on his test results which indicated the possibility of septic meningitis. He was started on treatment with high-dose antibiotics and steroids. On the third day of hospitalization, he became afebrile with improvement in his general status and was discharged on the sixth day. He had no developmental problems for up to 1 year after discharge. Metagenomic ribonucleic acid-Seq pathogen detection using next generation sequencing of a sample of his cerebrospinal fluid, which was collected at admission, revealed three short reads homologous to those in torque teno virus out of a total of 1,708,516 reads. This finding indicated that our patient was positive compared to the torque teno virus-negative cerebrospinal fluid samples (controls) from 13 other patients. The torque teno virus has been shown to have a whole genome sequence of 2810?nt by polymerase chain reaction. We prepared a recombinant GP2 antigen from torque teno virus and used it to study our patient's anti-torque teno virus immune response. An anti-GP2 serum immunoglobulin M response was detected, providing further supportive evidence of torque teno virus infection. CONCLUSIONS:This case speculates that torque teno virus-induced aseptic meningitis has a good course. New technologies like next generation sequencing can help in the identification of such cases, and an accumulation of future cases is expected.
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Project description:BackgroundAlong with the increasing use of immune checkpoint inhibitors comes a surge in immune-related toxicity. Here, we review the currently available data regarding neurological immune adverse events, and more specifically aseptic meningitis and encephalitis, and present treatment and diagnostic recommendations. Furthermore, we present five cases of immunotherapy-induced aseptic meningitis and encephalitis treated at our institution.Recent findingsNeurological immune-related adverse events, including aseptic meningitis and encephalitis, secondary to checkpoint inhibitors are a rare but complex and clinically relevant entity, comprising a wide range of diseases, most often presenting with symptoms with a wide range of differential diagnoses. Our case-series highlights the challenges of such entities and the importance of properly identifying and managing aseptic meningitis and encephalitis.SummaryCheckpoint inhibitor-induced meningoencephalitis warrants prompt investigations and treatment. Properly diagnosing aseptic meningitis, encephalitis, or mixed presentations may guide the treatment decision, as highlighted by our case-series. After rapid exclusion of alternative diagnoses, urgent corticosteroids are the therapeutic backbone but this could change in favour of highly specific cytokine-directed treatment options.Plain language summaryAseptic meningitis and encephalitis with immune checkpoint inhibitors: a single centre case-series and review of the literature Over the course of the past decade, checkpoint inhibitors have revolutionized cancer care. With their favourable toxicity profile and potential for durable and deep responses, they have become ubiquitous across the field of oncology. Furthermore, combination checkpoint inhibitors are also gaining ground, with increased efficacy and, unfortunately, immune-related toxicity. While there are guidelines based on extensive clinical experience for frequent adverse events, uncommon entities are less readily identified and treated. Neurological immune-related adverse events secondary to checkpoint inhibitors are a rare but complex entity, comprising a wide range of diseases, most often presenting with aspecific symptoms. In this paper, we discuss a single institution case-series of patients with autoimmune aseptic meningitis and encephalitis, and we perform a narrative literature review on this subject. We conclude with our treatment recommendations based on available evidence.
| S-EPMC8010823 | biostudies-literature
Project description:Craniopharyngiomas (CPs) are benign tumors that are believed to arise from embryonic remnants of the Rathke pouch epithelium. Herein, we report a case of aseptic meningitis due to spontaneous rupture of multicystic CP, which contained an Ommaya catheter. A 19-year-old boy was admitted to the hospital with a 4-day history of acute severe headache after strenuous physical exercise followed by altered sensorium, fever, and neck stiffness. Cerebrospinal fluid (CSF) analysis revealed marked pleocytosis and elevated protein levels. CSF culture was otherwise negative. Cyst reduction on subsequent imaging confirmed the diagnosis. The patient received intravenous steroid therapy and was discharged asymptomatic. This is a rare evolution of a multicystic CP, which was previously treated with intracystic therapy and had an Ommaya catheter. Clinicians should be aware of spontaneous CP rupture and look actively for the occurrence of cholesterol crystals or elevated CSF levels of cholesterol as well as prompt follow-up imaging.
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Project description:Echovirus 18 has been recognized as an important causative pathogen of aseptic meningitis in young children worldwide, and echovirus 18-induced meningitis is rarely found in adults with immunocompetence. In this case study, we report the clinical and virological characteristics of aseptic meningitis caused by recombinant echovirus 18 in an adult with immunocompetence. A 31-year-old woman with immunocompetence was admitted to our hospital with fever, dizziness, severe headache, nausea, and vomiting for the past 1 day and was diagnosed with viral meningitis based on the clinical manifestations and laboratory results from cerebrospinal fluid (CSF). The patient received antiviral treatment with ribavirin and interferon as soon as the enterovirus infection was identified using qRT-PCR and was cured after 4 days. From the oropharyngeal swab and CSF samples, two echovirus 18 strains were isolated with a single nucleotide difference located at the 5' UTR. Phylogenetic analyses based on the VP1 gene showed that the two strains belonged to the subgenotype C2 and were clustered with sequences obtained from China after 2015, while the results from the 3D polymerase region showed that the two strains were closely related to the E30 strains. Bootscanning results using the 5' UTR to 2A region and the 2B to 3' UTR region showed that potential intertypic recombination had occurred in the 2B gene. Recombination analyses further confirmed that the two strains (echovirus 18) presented genome recombination with echovirus 30 in the nucleotide regions of the 2B gene. To the best of our knowledge, this is the first report of echovirus 18-induced meningitis in an adult with immunocompetence from mainland China, highlighting the need for close surveillance of echovirus 18 both in children and adults in the future.
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Project description:Skin and skin-structure infections are common in ambulatory settings. However, the efficacy of various antibiotic regimens in the era of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) is unclear.We enrolled outpatients with uncomplicated skin infections who had cellulitis, abscesses larger than 5 cm in diameter (smaller for younger children), or both. Patients were enrolled at four study sites. All abscesses underwent incision and drainage. Patients were randomly assigned in a 1:1 ratio to receive either clindamycin or trimethoprim-sulfamethoxazole (TMP-SMX) for 10 days. Patients and investigators were unaware of the treatment assignments and microbiologic test results. The primary outcome was clinical cure 7 to 10 days after the end of treatment.A total of 524 patients were enrolled (264 in the clindamycin group and 260 in the TMP-SMX group), including 155 children (29.6%). One hundred sixty patients (30.5%) had an abscess, 280 (53.4%) had cellulitis, and 82 (15.6%) had mixed infection, defined as at least one abscess lesion and one cellulitis lesion. S. aureus was isolated from the lesions of 217 patients (41.4%); the isolates in 167 (77.0%) of these patients were MRSA. The proportion of patients cured was similar in the two treatment groups in the intention-to-treat population (80.3% in the clindamycin group and 77.7% in the TMP-SMX group; difference, -2.6 percentage points; 95% confidence interval [CI], -10.2 to 4.9; P=0.52) and in the populations of patients who could be evaluated (466 patients; 89.5% in the clindamycin group and 88.2% in the TMP-SMX group; difference, -1.2 percentage points; 95% CI, -7.6 to 5.1; P=0.77). Cure rates did not differ significantly between the two treatments in the subgroups of children, adults, and patients with abscess versus cellulitis. The proportion of patients with adverse events was similar in the two groups.We found no significant difference between clindamycin and TMP-SMX, with respect to either efficacy or side-effect profile, for the treatment of uncomplicated skin infections, including both cellulitis and abscesses. (Funded by the National Institute of Allergy and Infectious Diseases and the National Center for Advancing Translational Sciences, National Institutes of Health; ClinicalTrials.gov number, NCT00730028.).
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Project description:BACKGROUND:U.S. emergency department visits for cutaneous abscess have increased with the emergence of methicillin-resistant Staphylococcus aureus (MRSA). The role of antibiotics for patients with a drained abscess is unclear. METHODS:We conducted a randomized trial at five U.S. emergency departments to determine whether trimethoprim-sulfamethoxazole (at doses of 320 mg and 1600 mg, respectively, twice daily, for 7 days) would be superior to placebo in outpatients older than 12 years of age who had an uncomplicated abscess that was being treated with drainage. The primary outcome was clinical cure of the abscess, assessed 7 to 14 days after the end of the treatment period. RESULTS:The median age of the participants was 35 years (range, 14 to 73); 45.3% of the participants had wound cultures that were positive for MRSA. In the modified intention-to-treat population, clinical cure of the abscess occurred in 507 of 630 participants (80.5%) in the trimethoprim-sulfamethoxazole group versus 454 of 617 participants (73.6%) in the placebo group (difference, 6.9 percentage points; 95% confidence interval [CI], 2.1 to 11.7; P=0.005). In the per-protocol population, clinical cure occurred in 487 of 524 participants (92.9%) in the trimethoprim-sulfamethoxazole group versus 457 of 533 participants (85.7%) in the placebo group (difference, 7.2 percentage points; 95% CI, 3.2 to 11.2; P<0.001). Trimethoprim-sulfamethoxazole was superior to placebo with respect to most secondary outcomes in the per-protocol population, resulting in lower rates of subsequent surgical drainage procedures (3.4% vs. 8.6%; difference, -5.2 percentage points; 95% CI, -8.2 to -2.2), skin infections at new sites (3.1% vs. 10.3%; difference, -7.2 percentage points; 95% CI, -10.4 to -4.1), and infections in household members (1.7% vs. 4.1%; difference, -2.4 percentage points; 95% CI, -4.6 to -0.2) 7 to 14 days after the treatment period. Trimethoprim-sulfamethoxazole was associated with slightly more gastrointestinal side effects (mostly mild) than placebo. At 7 to 14 days after the treatment period, invasive infections had developed in 2 of 524 participants (0.4%) in the trimethoprim-sulfamethoxazole group and in 2 of 533 participants (0.4%) in the placebo group; at 42 to 56 days after the treatment period, an invasive infection had developed in 1 participant (0.2%) in the trimethoprim-sulfamethoxazole group. CONCLUSIONS:In settings in which MRSA was prevalent, trimethoprim-sulfamethoxazole treatment resulted in a higher cure rate among patients with a drained cutaneous abscess than placebo. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00729937.).
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Project description:Trimethoprim (TMP)-sulfamethoxazole (SMX) is a widely used synergistic antimicrobial combination to treat a variety of bacterial and certain fungal infections. These drugs act by targeting sequential steps in the biosynthetic pathway for tetrahydrofolate (THF), where SMX inhibits production of the THF precursor dihydropteroate, and TMP inhibits conversion of dihydrofolate (DHF) to THF. Consequently, SMX potentiates TMP by limiting de novo DHF production and this mono-potentiation mechanism is the current explanation for their synergistic action. Here, we demonstrate that this model is insufficient to explain the potent synergy of TMP-SMX. Using genetic and biochemical approaches, we characterize a metabolic feedback loop in which THF is critical for production of the folate precursor dihydropterin pyrophosphate (DHPPP). We reveal that TMP potentiates SMX activity through inhibition of DHPPP synthesis. Our study demonstrates that the TMP-SMX synergy is driven by mutual potentiation of the action of each drug on the other.
| S-EPMC5843663 | biostudies-literature
Project description:BackgroundMelioidosis, an infectious disease caused by the Gram-negative bacillus Burkholderia pseudomallei, is difficult to cure. Antimicrobial treatment comprises intravenous drugs for at least 10 days, followed by oral drugs for at least 12 weeks. The standard oral regimen based on trial evidence is trimethoprim-sulfamethoxaxole (TMP-SMX) plus doxycycline. This regimen is used in Thailand but is associated with side-effects and poor adherence by patients, and TMP-SMX alone is recommended in Australia. We compared the efficacy and side-effects of TMP-SMX with TMP-SMX plus doxycycline for the oral phase of melioidosis treatment.MethodsFor this multi-centre, double-blind, non-inferiority, randomised placebo-controlled trial, we enrolled patients (aged ≥15 years) from five centres in northeast Thailand with culture-confirmed melioidosis who had received a course of parenteral antimicrobial drugs. Using a computer-generated sequence, we randomly assigned patients to receive TMP-SMX plus placebo or TMP-SMX plus doxycycline for 20 weeks (1:1; block size of ten, stratified by study site). We followed patients up every 4 months for 1 year and annually thereafter to the end of the study. The primary endpoint was culture-confirmed recurrent melioidosis, and the non-inferiority margin was a hazard ratio (HR) of 1.7. This study is registered with www.controlled-trials.com, number ISRCTN86140460.FindingsWe enrolled and randomly assigned 626 patients: 311 to TMP-SMX plus placebo and 315 to TMP-SMX plus doxycycline. 16 patients (5%) in the TMP-SMX plus placebo group and 21 patients (7%) in the TMP-SMX plus doxycycline group developed culture-confirmed recurrent melioidosis (HR 0.81; 95% CI 0.42-1.55). The criterion for non-inferiority was met (p=0.01). Adverse drug reactions were less common in the TMP-SMX plus placebo group than in the TMP-SMX plus doxycycline group (122 [39%] vs 167 [53%]).InterpretationOur findings suggest that TMP-SMX is not inferior to TMP-SMX plus doxycycline for the oral phase of melioidosis treatment, and is preferable on the basis of safety and tolerance by patients.FundingThailand Research Fund, the Melioidosis Research Center, the Center of Excellence in Specific Health Problems in Greater Mekong Sub-region cluster, and the Wellcome Trust.
| S-EPMC3939931 | biostudies-literature
Project description:Trimethoprim (TMP)-sulfamethoxazole (SMX) is used to treat various types of infections, including community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) and Pneumocystis jirovecii infections in children. Pharmacokinetic (PK) data for infants and children are limited, and the optimal dosing is not known. We performed a multicenter, prospective PK study of TMP-SMX in infants and children. Separate population PK models were developed for TMP and SMX administered by the enteral route using nonlinear mixed-effects modeling. Optimal dosing was determined on the basis of the matching adult TMP exposure and attainment of the surrogate pharmacodynamic (PD) target for efficacy, a free TMP concentration above the MIC over 50% of the dosing interval. Data for a total of 153 subjects (240 samples for PK analysis) with a median postnatal age of 8 years (range, 0.1 to 20 years) contributed to the analysis for both drugs. A one-compartment model with first-order absorption and elimination characterized the TMP and SMX PK data well. Weight was included in the base model for clearance (CL/F) and volume of distribution (V/F). Both TMP and SMX CL/F increased with age. In addition, TMP and SMX CL/F were inversely related to the serum creatinine and albumin concentrations, respectively. The exposure achieved in children after oral administration of TMP-SMX at 8/40 mg/kg of body weight/day divided into administration every 12 h matched the exposure achieved in adults after administration of TMP-SMX at 320/1,600 mg/day divided into administration every 12 h and achieved the PD target for bacteria with an MIC of 0.5 mg/liter in >90% of infants and children. The exposure achieved in children after oral administration of TMP-SMX at 12/60 and 15/75 mg/kg/day divided into administration every 12 h matched the exposure achieved in adults after administration of TMP-SMX at 640/3,200 mg/day divided into administration every 12 h in subjects 6 to <21 years and 0 to <6 years of age, respectively, and was optimal for bacteria with an MIC of up to 1 mg/liter.
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