|Year : 2022 | Volume
| Issue : 2 | Page : 205-207
Tubercular meningitis complicated by weil's Syndrome – Management of tuberculosis in a patient with concurrent hepatic and renal dysfunction
Chaudhary Niraliben Hareshkumar, Prashant Gopal, Pradnya Mukund Diggikar
Department of General Medicine, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, Maharashtra, India
|Date of Submission||07-Apr-2022|
|Date of Decision||20-May-2022|
|Date of Acceptance||28-May-2022|
|Date of Web Publication||14-Jun-2022|
|Date of Print Publicaton||14-Jun-2022|
Pradnya Mukund Diggikar
Plot No. 51, B. R. Rao Nagar, Old Alwal, Secunderabad - 500 010, Telangana
Source of Support: None, Conflict of Interest: None
Weil's syndrome, a severe form of the disease, may present with symptoms such as jaundice, renal dysfunction, and hemorrhagic diathesis and it can progress to multi-organ failure leading to death. In patients with coinfection of tuberculosis with leptospirosis, there may be severe hepatic and renal dysfunction rendering the standard antitubercular therapy (ATT) regimen useless, thus requiring alternate drug selection and dose modification of antitubercular drugs. We present a case of a 57-year-old female who presented with high-grade fever and yellowish discoloration of the eyes. She was diagnosed with Weil's disease and started on treatment. She later developed altered sensorium and lumbar puncture was suggestive of tubercular meningitis. Due to her deranged renal and hepatic function tests, she was started on a modified regimen of ATT with intermittent dialysis. The patient responded to treatment and was shifted to the standard Isoniazid, Rifampicin, Pyrazinamide, Ethambutol (HRZE) regimen once renal and hepatic functions returned to normal.
Keywords: Extrapulmonary, hepatic dysfunction, leptospirosis, meningitis, renal, tuberculosis, Weil's
|How to cite this article:|
Hareshkumar CN, Gopal P, Diggikar PM. Tubercular meningitis complicated by weil's Syndrome – Management of tuberculosis in a patient with concurrent hepatic and renal dysfunction. Int J Mycobacteriol 2022;11:205-7
|How to cite this URL:|
Hareshkumar CN, Gopal P, Diggikar PM. Tubercular meningitis complicated by weil's Syndrome – Management of tuberculosis in a patient with concurrent hepatic and renal dysfunction. Int J Mycobacteriol [serial online] 2022 [cited 2022 Jul 6];11:205-7. Available from: https://www.ijmyco.org/text.asp?2022/11/2/205/347518
| Introduction|| |
Leptospirosis, caused by pathogenic species of the spirochete bacterium Leptospira, is the most common zoonotic infection in the world, occurring more commonly in tropical and subtropical regions, where the climate and often poor hygienic conditions favor its survival and distribution. Weil's syndrome, a severe form of the disease, may present with symptoms such as jaundice, renal dysfunction, and hemorrhagic diathesis and it can progress to multi-organ failure leading to death. Higher mortality rates are associated with age >40 years, acute renal failure, respiratory insufficiency, altered mental status, hypotension, and arrhythmias.
Tuberculosis (TB) is an infectious disease usually caused by Mycobacterium TB bacteria, an intracellular acid-fast bacilli. The two types of clinical manifestations of TB include pulmonary TB (PTB), primarily involving the lungs and extra PTB (EPTB), involving organs other than the lungs, for example, pleura, lymph nodes, abdomen, genitourinary tract, skin, joints, and bones, or meninges. EPTB can occur in up to 20% of immunocompetent people. EPTB can occur secondary to hematogenous or lymphatic spread. Tubercular meningitis is the most severe form of EPTB, and it carries a high incidence of morbidity and mortality. The treatment of TB usually involves the use of a multi-drug regimen to prevent resistance. This treatment is complicated in cases of coinfection with leptospirosis as there may be severe hepatic and renal dysfunction rendering the standard antitubercular therapy regimen useless, thus requiring alternate drug selection and dose modification of antitubercular drugs.
| Case Report|| |
A 57-year-old female, farmer by occupation with a history of diabetes mellitus for 11 years and hypertension for 7 years on regular medication presented with a history of fever for the past 7 days and yellowish discoloration of the eyes for the past 4 days. She had no history of other drugs or alternate medication use. Fever was high grade, without diurnal variation and was relieved on taking medications. Blood pressure was 126/74 mmHg, temperature was 37.2°C, pulse rate was 96 beats/min, and respiratory rate was 22 cycles/min. The patient was alert and oriented to time, place, and person. Systemic examination revealed mild hepatomegaly. Laboratory investigations showed leukocytosis, thrombocytopenia, deranged hepatic and renal functions, hematuria, and raised inflammatory markers [Table 1]. Venous blood gas (VBG) analysis showed metabolic acidosis with decompensated respiratory alkalosis. Rapid immunoglobulin M test for Leptospira came back positive. Ultrasound-arterioportography showed mild hepatomegaly. High-resolution computed tomography (CT) of the thorax showed no abnormalities. The patient was started on injection ceftriaxone 1 g IV BD and tablet doxycycline 100 mg P/O BD. Hemodialysis was done three times in the 1st week of admission in view of deranged serum creatinine levels and persistent acidosis on VBG.
On day 3 of admission, the patient developed altered sensorium. Fundus examination and CT brain were normal. Kernig's and Brudzinski's were positive. Cerebrospinal fluid (CSF) analysis showed a total leukocyte count (TLC) of 400 cells (90% lymphocytes), proteins of 756 mg/dl, glucose of 42 mg/dl (BSL-R 124), and adenosine deaminase levels of 46 (normal <30). CSF for CBNAAT came back positive of M. TB with no resistance to isoniazid (INH) or rifampicin (RIF). The patient was started on tablet streptomycin 15 mg/kg, tablet levofloxacin 15 mg/kg, and tablet c (EMB) 15 mg/kg every alternate day postdialysis considering her deranged hepatic and renal functions, which were regularly monitored. Injection dexamethasone 8 mg Tax deduction at source IV was started and tapered over 4 weeks.
By day 6, the patient's sensorium returned to normal and she showed improved renal and hepatic functions. Platelet counts were 154,000 cells/μl and TLC was 11,200 cells/μl. Renal function tests (RFT) returned to normal by day 9. Bilirubin and Liver function tests (LFT) returned to normal by day 13. Once RFTs and LFTs returned to normal, the patient was shifted to the standard HRZE regimen (tablet INH 5 mg/kg, tablet RIF 10 mg/kg, tablet pyrazinamide (PZA) 25 mg/kg, and tablet EMB 15 mg/kg) daily. The patient was on regular follow-up and 6 months postdischarge. The patient showed no neurological deficits, and routine laboratory investigations were normal.
| Discussion|| |
The World Health Organization recommends using four first-line TB medications, namely INH, RIF, PZA, and EMB, for the treatment of drug-susceptible TB for at least 6 months in cases of PTB and 9 months in cases of tubercular meningitis. INH, RIF, and PZA are the first-line drugs associated with hepatotoxicity.
RIF is a bactericidal agent that is least likely to cause hepatocellular damage, although it has been linked to cholestatic jaundice on rare occasions. The bactericidal drug INH is metabolized in the liver, and its toxicity is mediated by its metabolite hydrazine. PZA is a bactericidal agent that can exhibit both dose-dependent and idiosyncratic hepatotoxicity and is probably the most hepatotoxic. A hepatotoxic-free regimen is required in patients with severe unstable liver disease and an injectable drug such as streptomycin or amikacin/kanamycin, EMB, a fluoroquinolone, and another second-line oral drug may be used for 18–24 months.
In patients with renal insufficiency with a creatinine clearance of <30 ml/min, standard guidelines recommend full doses of INH and RIF (biliary excretion), with PZA and EMB given in doses of 25 mg/kg and 15 mg/kg, respectively, three times weekly. Postdialysis administration can help avoid premature drug removal, but there is an increased risk of toxicity.
No protocols exist for the treatment of TB in patients with both hepatic and renal dysfunctions. After reviewing the available literature [Table 2] and upon consultation with an infectious disease specialist, we concluded that only a few second-line drugs, such as linezolid, could be safely administered in patients with both hepatic and renal dysfunctions. However, long-term administration of linezolid (>28 days) was associated with an increased risk of hematological toxicity and peripheral neuropathy in patients with renal dysfunction.
|Table 2: Standard recommendations of antitubercular drugs in hepatic and renal dysfunctions|
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Since it is recommended that a multi-drug regimen be used to increase efficacy and to prevent resistance, and as our patient was undergoing hemodialysis, she was started on a regimen of tablet streptomycin 15 mg/kg, tablet levofloxacin 15 mg/kg, and tablet EMB 15 mg/kg every alternate day postdialysis with regular monitoring of hepatic and renal functions. The patient was monitored for ototoxicity and neurological deterioration, with dose modifications planned as necessary. Our patient responded to treatment with no decline in hepatic and renal functions and was shifted to the standard HRZE regimen once renal and hepatic functions returned to normal.
| Conclusion|| |
Treatment of TB in hepatic or renal dysfunction by itself poses a significant challenge. In patients with both hepatic and renal dysfunctions simultaneously, great caution should be used regarding the selection of drug regimens and doses. Regular monitoring of hepatic and renal functions and dose modification as required is necessary. Further research and standardization of drug regimen protocols are required.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her names and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]