Antimicrobial therapy is indicated for the severe form of leptospirosis, but its use is controversial for the mild form of leptospirosis. A Cochrane Review found insufficient evidence to advocate for or against the use of antibiotics in the therapy for leptospirosis. 
If antibiotics are used, they should be initiated as soon as the diagnosis of leptospirosis is considered and should be continued for a full course despite initial serologic results, because most patients are diagnosed only through acute and convalescent testing. Early treatment has been shown to offer the best clinical outcomes; results from controlled studies of treatment during the immune phase have yielded mixed results. [43, 44]
Mild leptospirosis is treated with doxycycline, ampicillin, or amoxicillin. For severe leptospirosis, intravenous penicillin G has long been the drug of choice, although the third-generation cephalosporins cefotaxime and ceftriaxone have become widely used. Alternative regimens are ampicillin, amoxicillin, or erythromycin. Several other antibiotics may be useful—for example, broth microdilution testing has shown sensitivity to macrolides, fluoroquinolones, and carbapenems  —but clinical experience with these agents is more limited.
Severe cases of leptospirosis can affect any organ system and can lead to multiorgan failure. Supportive therapy and careful management of renal, hepatic, hematologic, and central nervous system complications are important.
Patients should be managed in a monitored setting because their condition can rapidly progress to cardiovascular collapse and shock. Access to mechanical ventilation and airway protection should be available in the event of respiratory compromise. Continuous cardiac monitoring should be attained; arrhythmias, including ventricular tachycardia and premature ventricular contractions, as well as atrial fibrillation, flutter, and tachycardia, can occur.
Renal function should be evaluated carefully and dialysis considered in cases of renal failure. In most cases, the renal damage is reversible if the patient survives the acute illness. Early initiation of hemodialysis or peritoneal dialysis considerably reduces mortality risk. A few cases in the literature have reported that plasma exchange, corticosteroids, and intravenous immunoglobulin may be beneficial in selected patients in whom conventional therapy does not elicit a response. [46, 47, 48]
Corticosteroid therapy is controversial. A 2014 review suggests lack of benefit and possible increased risk of nosocomial infection.  As with severity of illness, response may vary depending on host immune factors or the particular virulence of the leptospire. Treatment with high-dose pulsed methylprednisolone (30 mg/kg/d, not to exceed 1500 mg) has been used successfully to treat patients with leptospiral renal failure without dialysis. This approach may have be beneficial in resource-poor areas where dialysis is unavailable and would involve lengthy medical transport. The use of renal-dose dopamine in conjunction with steroids or diuretics has also been described. 
Pulse-dose steroids may also play a role early in the management of severe pulmonary disease. [50, 47] Patients with Weil syndrome may need transfusions of whole blood, platelets, or both. Ophthalmic drops of mydriatics and corticosteroids have been used for relief of ocular symptoms. 
Patients with severe disease should remain hospitalized until adequate resolution of organ failure and clinical infection. Outpatient follow-up may include an assessment of renal function to ensure ongoing reversal of any damage. A cardiac assessment may be indicated in patients with symptoms suggestive of heart involvement.
Diet and Activity
In mild cases, patients should be encouraged to maintain adequate fluid intake to avoid volume depletion. In more severe cases, diets appropriate for the clinical picture should be ordered (eg, electrolyte and protein restriction in cases of renal insufficiency). Patients with hypotension or clinical shock should not be fed enterally until adequate perfusion is restored.
Patients with severe disease should be placed on bed rest until adequately resuscitated and treated. Those with mild disease can pursue activity as tolerated.
Transfer to a facility with an appropriate level of care should be considered in patients with severe disease. Leptospirosis has a regional epidemiology with high incidence of cases in remote regions that offer limited medical care. Although transporting patients with severe disease to appropriate medical centers is preferred, military physicians who have treated patients from Western Pacific islands averted the need for transoceanic transport for dialysis by administering high-dose steroids. [38, 37]
In severe cases of leptospirosis, several specialty consultations may aid in proper patient management. An infectious disease specialist may assist in differentiating leptospirosis from diseases with similar presentations but that may have significantly different treatments. A nephrologist should be alerted early in the course because the need for dialysis may develop rapidly. If available, critical care specialists may be best prepared to manage patients with affected multiple systems.
For assistance with laboratory diagnosis, the Centers for Disease Control and Prevention (CDC) or the World Health Organization (WHO) can aid the clinician in obtaining samples and ordering tests.
Prevention of leptospirosis is difficult because the organism has not been eradicated from wild animals, which constantly infect domestic animals. Important control measures include control of livestock infection with good sanitation, immunization, and proper veterinary care.
Preventing infected animals from urinating in waters where humans have contact, disinfecting contaminated work areas, providing worker education, practicing good personal hygiene, and using personal protective equipment (PPE) when handling infected animals or tissues are important actions for prevention of the disease. Examples of PPE include gloves and face shields for veterinarians and rubber boots for sewer workers and agricultural workers who wade in rodent urine-contaminated water.
Public health measures include investigation of cases in an effort to detect common source outbreaks and implementation of appropriate control measures to prevent further cases. Other public health measures include identification of contaminated water supplies, rodent control, prohibition of swimming in streams where risk of infection may be high, and informing people of risk when they are involved in recreational activities.
Vaccines are offered to high-risk workers in some European and Asian countries (eg, rice workers in Italy). Human vaccines are serovar specific and must be repeated yearly. They are associated with painful swelling, especially after revaccination. Vaccines are not used in the United States.
However, renal infection and persistent leptospiruria can occur in immunized dogs. Human infection has occurred from asymptomatic immunized dogs that still shed leptospires in their urine. Also, these animal vaccines are serovar specific and thus are useful only where one or a few serovars are present. Hence, the vaccine given should contain the serovars known to be prevalent in the area.
Doxycycline, in the dose of 200 mg every week, has demonstrated efficacy of 95% against leptospirosis and may help prevent the disease in exposed adults. [52, 53] This regimen is recommended for those with short-term exposure and is not for repeated or long-term exposure. The role of prophylaxis in children has not been adequately studied.
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