Approach

Effective management of leptospirosis involves a combination of antibiotic therapy and appropriate supportive therapy. Identifying cases of leptospirosis and initiating treatment promptly is paramount, as a systematic review that assessed the mortality of untreated leptospirosis found a median mortality of 2.2%, with a broad range of 0% to 39.7%.[73] The mortality rates were highest in patients with jaundice (19.1%), those with renal failure (12.1%), and older patients aged >60 years (60%).[73]

Antibiotic therapy

It is generally accepted that antibiotic therapy should be initiated as soon as possible, preferably during the first 5 days of the appearance of symptoms.

Antibiotic recommendations for the management of leptospirosis are provided according to disease presentation. Preferred antibiotic agents include oral doxycycline for mild disease and intravenous benzylpenicillin for the management of severe cases.[50][74][75]

Patients must be carefully monitored for adverse reactions including the Jarisch-Herxheimer reaction, which can be fatal.[76] One retrospective study of 262 patients in New Caledonia found that the reaction occurred in 21% of treated patients.[77]

Mild disease

The recommended oral antibiotic for adults and children with mild leptospirosis is doxycycline (not recommended in children 8 years of age or less), with ampicillin, azithromycin, or amoxicillin as alternative first-line agents.[50] The treatment course is 7 days (except azithromycin, for which the treatment course is 3 days in adults and is not yet established in children).

Moderate to severe disease

Moderate to severe leptospirosis in adults and children is treated with intravenous antibiotic therapy. Benzylpenicillin is recommended as the first-line treatment, with ceftriaxone or cefotaxime as alternative first-line agents.[50][57][74][75] Ceftriaxone and cefotaxime have shown equivalent clinical efficacy when compared with benzylpenicillin for the management of severe leptospirosis.[74][78][79] Adults with penicillin and/or cephalosporin allergy should be treated with azithromycin (not recommended below the age of 16 years) or doxycycline. Children with such an allergy should be treated with doxycycline.[75] Doxycycline and other tetracycline antibiotics may cause permanent tooth discolouration or enamel hypoplasia and are not recommended in children 8 years of age or less. However, their use in this patient group may be considered on a case-by-case basis in severe leptospirosis, where the clinician should evaluate the benefits and risks of such treatment. Erythromycin is a possible alternative and can be given to children below the age of 8 years. Intravenous therapy is recommended for 7 days.

Supportive therapy

The type and degree of supportive measures required in patients with leptospirosis are highly variable and are assessed individually according to the organ involvement.

Severe disease is associated with the immune phase and may manifest with renal failure, hepatic failure, and /or pulmonary haemorrhages (Weil syndrome). Other presentations during this phase include aseptic meningitis and pancreatitis. Death may occur secondary to cardiac arrhythmias, cardiac failure, or adrenal haemorrhage, hence the need for ongoing cardiac monitoring and support if required.

Overall, patients must be monitored for changes consistent with volume depletion and haemorrhage. Physicians should correct coagulopathy and electrolyte disturbances and ensure adequate hydration.

Patients with pulmonary involvement, with or without haemorrhage, may require mechanical ventilation. Intravenous methylprednisolone has been used successfully in patients with pulmonary leptospirosis, but one systematic review found limited evidence; further trials are needed to determine whether corticosteroids should routinely be given to patients with severe leptospirosis and pulmonary involvement.[80][81]

Patients with acute renal failure may require acute dialysis in severe disease, taking into consideration the symptoms of fluid overload, acidosis, and hyperkalaemia. The decision must be made on a case-by-case basis. Patients with hepatic failure usually only require intravenous antibiotic therapy and supportive care.

Cardiac monitoring is recommended for timely identification of arrhythmias secondary to cardiac irritability. Cardiac arrhythmias should be managed according to recognised guidelines such as those from the American College of Cardiology (ACC), American Heart Association (AHA), and European Society of Cardiology (ESC).

Patients at high risk of exposure

Doxycycline chemoprophylaxis has been used in military personnel without known previous exposure. Hikers, bikers, and adventurous travellers may consider doxycycline prophylaxis due to high risk of leptospirosis present in developing countries.[46] Other people at risk of exposure include those travelling to high-risk areas after natural disasters, such as flooding or cyclone, or during high-risk seasons, and athletes participating in water sports.[29][30][31][82] Peak incidence occurs during the rainy season in tropical areas and during the late summer in temperate regions.[1][7]

Doxycycline prophylaxis is recommended for people at risk of unavoidable exposure.

Data suggest that azithromycin is a viable alternative for prophylaxis, as head-to-head studies have shown similar reductions in seropositivity.[47]

One observational study has concluded that oral penicillin may be effective chemoprophylaxis against leptospirosis; however, further research is needed.[48]

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