a) Moderate hepatomegaly may be noted in 10% to 40% of patients; liver may be tender (Malik, 1997; Mohd, 1989) Mousa, 1988; Al-Eissa, 1990; (Benjamin & Annobil, 1992). This may be more common in children; in 5 pediatric studies, incidences between 27% and 69% were noted (Galanakis, 1996; Gottesman, 1996).

a) Patients may present with UTI symptoms, including dysuria (Mousa, 1988; Robson, 1993; Yinnon, 1993). In one large series, brucellosis was highly associated with prostatitis in men (Colmenero, 1996).

a) Patients may present with UTI symptoms, including suprapubic or loin pain (Mousa, 1988).
b) Testicular edema and pain may be present in males with epididymo-orchitis (Lulu, 1988; (Khan et al, 1989) Patel, 1988; Reisman, 1990).

a) Patients may present with UTI symptoms, including urinary frequency and urgency, especially during the subacute and chronic stages (Lulu, 1988; Mousa, 1988). In one large series, brucellosis was highly associated with prostatitis in men (Colmenero, 1996).

a) Impotence may occur in patients with chronic infection (Trujillo, 1994; (Radolf, 1994).

a) Orchitis is usually unilateral; presents with acute scrotal pain and swelling, with little or no dysuria; does not cause sterility; also may involve epididymis and may be bilateral (Patel, 1988; (Khan et al, 1989) Reisman, 1990; Ibrahim, 1988; (Afsar et al, 1993). Systemic symptoms precede genitourinary complaints in about 3/4 of cases, but may present simultaneously (Colmenero, 1996).

a) Diffuse interstitial nephritis with azotemia, proteinuria, and hypertension may occur with renal involvement (Trujillo, 1994; (Radolf, 1994). A case of acute focal bacterial nephritis with normal renal function has also been described (Loberant, 1995).

a) In one large series, prostatitis occurred in about 1% of male patients and presented with urinary symptoms (dysuria, frequency, urgency, sensation of incomplete voiding). Biopsy in 2 patients showed chronic inflammation with granuloma formation (Colmenero, 1996).

a) Most commonly, temperature is normal or slightly elevated in morning and rises in afternoon; maximum daily temperature ranges from 101 F to 104 F (Trujillo, 1994; (Radolf, 1994).
b) Chills may be present in up to 70% to 80% of patients in the acute or subacute stages (Al-Eissa, 1990; Lulu, 1988; Mousa, 1988; (Taylor & Perdue, 1989) Yinnon, 1993). Chills may occur in about 50% of patients during the chronic stage of illness (Lulu, 1988).

a) ACUTE disease - Night sweats is a common feature, present in up to 90% of patients (Al-Eissa, 1990; Lulu, 1988; Mousa, 1988; (Mohd, 1989) Shehabi, 1990); often profuse with characteristic moldy odor (Mousa, 1988).
b) CHRONIC disease - Increased sweating was noted in about two thirds of patients (Lulu, 1988).

a) Reported dermatologic manifestations include (Nagore, 1999; Ariza, 1989):
b) Rash does not appear to worsen prognosis and resolves within a few days after starting appropriate treatment (Nagore, 1999).

a) Muscle pain may be present in up to 75% of patients, most commonly during the subacute stage (Lulu, 1989; Mousa, 1987a, 1988; Khateeb, 1990; Robson, 1993; (Applebaum & Mathisen, 1997). It appears to be more common in children than adults (Zaks, 1995).

a) Back pain is the most frequent osteoarticular manifestation, present in 60% to 70% of patients (Malik, 1997) Cordero-Sanchez, 1990; Khateeb, 1990; (Taylor & Perdue, 1989) Mousa, 1988; Lulu, 1988; Robson, 1993; (Applebaum & Mathisen, 1997). It may be a nonspecific symptom in context of osteoarticular aches associated with the disease (Cordero-Sanchez, 1990) or may be related to sacroiliac involvement or involvement of spine and adjacent areas (Ozgul, 1998; Cordero-Sanchez, 1990; Rajapakse, 1987; Al-Rawi, 1989; Mohan, 1990; (Applebaum & Mathisen, 1997).
b) In acute brucellosis, pain is typically related to back muscles; in chronic cases, low back pain is a prominent feature (Bahar, 1988).

a) Joint pain without other signs of inflammation is a common complaint, noted in 1/3 of to 3/4 of cases; more common in children (peak in ages 2 to 6 yr) where incidences up to 83% have been noted (Malik, 1997) Zaks, 1995; Colmenero, 1996; Gottesman, 1996; Khateeb, 1990; (Sharda & Lubani, 1986) Mousa, 1987a, 1988; Al-Eissa, 1990; (Alvarez De Buergo et al, 1990; Mohd, 1989) Shehabi, 1990; Lulu, 1988; (Lubani et al, 1986a) Benjamin, 1992a; Yinnon, 1993).
b) Usually the joint paint is monoarticular and unilateral; sacroiliac joint, knee, and hip are affected most frequently; spine, ankle, sternoclavicular joint, shoulder, wrist, and elbow are involved less commonly (Lulu, 1988; Mousa, 1987a, 1988; Al-Essia, 1990; Khateeb, 1990; (Sharda & Lubani, 1986) Mousa, 1988; (Alvarez De Buergo et al, 1990; Lubani et al, 1986a) Benjamin, 1992a, 1994; Knapp, 1994; Berrocal, 1993).
c) Peripheral large joint involvement is more common in children and young adults (Alvarez De Buergo et al, 1990; Lubani et al, 1986a) Al-Essia, 1990; (Sharda & Lubani, 1986) Mousa, 1987a, 1988; Benjamin, 1992a, 1994; Knapp, 1994; Galanakis, 1996; Gottesman, 1996).
d) Involvement of small and centrally placed joints and spondylitis is often more common in adults (Mousa, 1987, 1988; Ariza, 1993; Colmenero, 1996).
e) Joint effusion may be present in patients with Brucella arthritis, particularly during the acute stage; primarily elicited in knee, ankle, and wrist joints (Khateeb, 1990; Mousa, 1987a; Al-Rawi, 1989; Benjamin, 1992a).

a) Arthritis is a complication of brucellosis and may be septic or reactive (Alvarex de Buergo, 1990; (Lubani et al, 1986a) Rajapakse, 1990; Bahar, 1988). It may occur during any stage (including relapses) but most common during acute and subacute stages (Khateeb, 1990; (Sharda & Lubani, 1986) Lulu, 1988; (Al-Rawi et al, 1987) 1989; Shaheen, 1988; (Alvarez De Buergo et al, 1990) Mousa, 1987a; Benjamin, 1992a; (Benjamin & Khan, 1994).
b) Incidence is highly variable (10% to 70%), depending on pathogenicity of species and diagnostic criteria (Madkour, 1988; Benjamin, 1992a). Brucellosis should be considered in patients with joint pain and fever who come from or have visited an endemic area or have other risk factors (Knapp, 1994; (Benjamin & Khan, 1994).
c) Onset may be acute or insidious; most typically occurs simultaneously with or shortly after onset of fever; usually associated with severe limitation of movement and joint pain and tenderness (Alvarez De Buergo et al, 1990) Mousa, 1987a; (Lubani et al, 1986a) Shaheen, 1988; (Al-Rawi et al, 1987) 1989; Benjamin, 1992a, 1994; Knapp, 1994; (Benjamin & Khan, 1994) Ariza, 1993).
d) Arthritis is typically monarticular and unilateral; sacroiliac joint most commonly involved in adults, followed by knee, hip, and ankle; spine, sternoclavicular joint, shoulder, wrist, and elbow involved less commonly (Lulu, 1988; Mousa, 1987a, 1988; Al-Essia, 1990; Khateeb, 1990; (Sharda & Lubani, 1986; Alvarez De Buergo et al, 1990; Lubani et al, 1986a) Al-Rawi, 1989; Shaheen, 1988; (Al-Rawi et al, 1987) 1989; Gotuzzo, 1987; Colemnero, 1991, 1996; Benjamin, 1992a, 1994; (Sankaran-Kutty et al, 1991) Berrocal, 1993; Al-Shahed, 1994; Knapp, 1994). Large peripheral joint (knee, hip) involvement is more common in children and young adults (Al-Essia, 1990; (Benjamin & Annobil, 1992) 1992a, 1994; Mousa, 1987a, 1988; (Lubani et al, 1986a) Knapp, 1994; Galanakis, 1996).
e) In most cases, the ESR is only moderately elevated and WBC count is normal with relative lymphocytosis. This, along with a more indolent presentation and moderate local signs of inflammation, helps differentiate from an acute septic arthritis (Lubani et al, 1986a).
f) CASE SERIES - In a prospective study of 263 patients with brucellosis, hip joint involvement was found in 33 (20.4%) of 162 patients with osteoarticular form of the disease. Patients with hip arthritis were younger, with a mean age of 23.7 years (+/- 19.9 years {range 4 to 69}), compared with a mean age of 39.7 years (+/- 18.2 years) in the patients without hip involvement. In 21 cases, the disease was acquired through direct contact with infected animals, 10 developed disease after ingestion of an incriminated product, and in 2 the origin was unknown. In 5 patients, hip arthritis was the only clinical feature of brucellosis exposure.

a) The incidence of brucellosis spondylitis is highly variable (2% to 60%); common manifestation of chronic brucellosis (Gonzalez-Gay, 1999; Bahar, 1988; (Sankaran-Kutty et al, 1991) Ariza, 1993); often associated with neurobrucellosis (Mousa, 1989; Mohan, 1990; Colmenero, 1991, 1992) or sacroiliitis (Ariza, 1993). It primarily involves the intervertebral area of the lumbar or dorsal spine; cervical spine and sacroiliac region involved less frequently (Mousa, 1987a; Bahar, 1988; Al-Rawi, 1989; Rajapakse, 1990; Mohan, 1990; Colmenero, 1991, 1992; Cordero, 1991; Al-Shahed, 1994).

a) Small, non-tender cervical, inguinal or axillary lymph nodes are present in 10% to 20% of patients (Mohd, 1989) Al-Eissa, 1990; Mousa, 1988). In one study, lymphadenopathy was present in 80% of children; other pediatric studies, however, have found much lower incidences and one found the incidence was not different from normal children (Yinnon, 19993; Galanakis, 1996; Gottesman, 1996).

a) Complications involving multiple organ systems occur in up to 30% of all patients, most commonly those infected with B melitensis or B suis; rate increases if treatment is delayed, and about 1/2 of patients with a diagnostic delay >3 months experience complications (Trujillo, 1994; (Radolf, 1994) Lulu, 1988; Colmenero, 1996). May be initial presentation (Gelfand et al, 1989) Jayakumar, 1988).

a) Patients with chronic brucellosis may develop abscesses in the liver, spleen, genitalia, spine, long bones, soft tissue, or brain (Pina, 1999; Trujillo, 1994; (Radolf, 1994) Vargas, 1991; (Al-Eissa, 1993a). In B suis infection, the spleen and liver may contain multiple abscesses that calcify and appear as round nodules on roentgenograms (Trujillo, 1994; (Radolf, 1994).

a) RECURRENT BRUCELLOSIS may recur within 1 to 3 months in about 5% of cases; due to relapse or reinfection; results in milder febrile illness. Uncommon in patients who receive appropriate therapy; usually represents focal suppurative complications. May occur in persons with continuing exposure, eg, veterinarians and abattoir workers (Trujillo, 1994; (Radolf, 1994).
b) Predictors of relapse include temperature of 38.3 C or higher, positive blood cultures at baseline, and duration of symptoms before treatment of more than 10 days (Solera, 1998). Relapses occur in up to 10% of treated patients, usually within 3 to 10 months after initial episode. Symptoms may be milder or more severe than in acute stage; CNS involvement possible (Chia et al, 1990). Relapses are more often related to failure to complete lengthy therapy or focal suppurative complications than to antibiotic resistance (Young, 1995). Extending duration of drug treatment to at least 6 weeks is associated with a reduced relapse rate (Malik, 1997).

a) Cardiac complications occurred in <2% of a large series; endocarditis is the most common complication and often fatal once established. It accounts for about 80% of deaths due to brucellosis. Most cases are due to B abortus or B melitensis, although cases secondary to B suis have also been reported (Al-Harthi, 1989; Lubani et al, 1986) Fernandez-Guerrero, 1987; Jeroudi, 1987; Jacobs, 1990; Colmenero, 1996; ((Hoover, 2000)). In over half of cases, a previously healthy valve is involved. The aortic valve is affected in over 75% of cases; mitral valve involvement is less common and more likely to occur with previous valvular damage (Al-Harthi, 1989) Jeroudi, 1987; Jacobs, 1990; (Delvecchio et al, 1991; Chan & Hardiman, 1993) Colmenero, 1996).
b) Failure to diagnose Brucella endocarditis usually is due to cultured blood being discarded after 8 days (cultures do not become positive for at least 8 days and even for as long as 6 weeks) (Al-Harthi, 1989). Echocardiography usually helpful in detecting valvular vegetations (Jeroudi, 1987; (Lubani et al, 1986)
c) Prolonged clinical and subclinical course is common. Virtually all patients require valve replacement, prolonged antibiotic therapy, or both (Chia et al, 1990; Al-Harthi, 1989) Jeroudi, 1987; Al-Kasab, 1988; Fernandez-Guerrero, 1987; (Delvecchio et al, 1991) Jacobs, 1990; (Chan & Hardiman, 1993) Colmenero, 1996; Cohen, 1997).

a) Cardiac manifestations of brucellosis should be suspected in patients presenting with a heart murmur and history of ingestion of unpasteurized milk or dairy products (Lubani et al, 1986).

a) Respiratory symptoms, including dyspnea, may be present in up to 25% of patients (Mousa, 1988). Although respiratory symptoms (cough, pleuritic chest pain, dyspnea) occur, they do not usually denote pneumonia (Franz et al, 1997).

a) Respiratory symptoms, including dry cough, may be present in up to 30% of patients (Mousa, 1988; Lulu, 1988; Lubani, 1989b; Garcia-Rodriguez, 1989; (Benjamin & Annobil, 1992) Robson, 1994; Yinnon, 1993).

a) Headache is a complaint in 20% to 75% of patients, especially during the chronic stage (Malik, 1997) Al-Eissa, 1990; (Mohd, 1989; Taylor & Perdue, 1989) Mousa, 1987a, 1988; Khateeb, 1990; Lulu, 1988; Yinnon, 1993).

a) Neurobrucellosis can imitate various neurologic syndromes and conditions. In endemic areas, this should be suspected in patients with obscure or unexplained neurologic deficits, even without a definite history of exposure (Bahemuka, 1988; Al-Eissa, 1995).

a) Fatigue, a typical symptom of acute febrile illness, occurs in up to 3/4 of patients; fatigue and weakness may be prolonged (Lulu, 1988; Colmenero, 1996).

a) Malaise is a typical symptom of acute febrile illness; it is a less common complaint among children (Al-Eissa, 1990; Mousa, 1987a; Benjamin, 1992a; Chomel, 1994; Robson, 1993; Yinnon, 1993; Galanakis, 1996; Gottesman, 1996).

a) NEUROBRUCELLOSIS - Involvement of central or peripheral nervous system occurs in 2% to 6% of adults (McLean et al, 1992) Bahemuka, 1988; Bashirm 1985; (Shakir, 1986) et al, 1989). This is rare in children, accounting for less than 1% of cases (Habeeb, 1998; (Omar et al, 1997). Although adult and pediatric neurobrucellosis have similar clinical spectrums, cases in adults can be either acute or chronic, whereas in children, it is usually an acute presentation. Peripheral nervous system involvement in isolation or in association with the CNS may occur in 1/3 of adults but has not been reported in children. Pediatric neurobrucellosis usually involves the CNS, and the clinical presentation is mainly as acute meningitis or meningoencephalitis (Habeeb, 1998).

a) Bacterial meningitis is an uncommon complication; it may present as an initial manifestation or at any time during the course of disease; it may follow a subclinical course or manifest as acute or chronic infection (Bouza, 1987; Mousa, 1986; (McLean et al, 1992; Al Deeb et al, 1989).
b) It mimics other neurologic and non-neurologic conditions; nuchal rigidity is present in only one third of patients (Bouza, 1987; Mousa, 1986). It may be associated with papilledema, optic neuropathy, or radiculopathy (McLean et al, 1992).
c) Isolation of Brucella from CSF is uncommon; serologic tests on CSF are preferred (Bouza, 1987; Mousa, 1986; Lubani, 1989a; Al-Eissa, 1995).
d) This has a better prognosis than other forms of chronic meningitis. It has a low mortality but high incidence of sequelae; may lead to disorders of vision and hearing, aphasia, ataxia, intermittent coma, hemiplegia (Bouza, 1987; (McLean et al, 1992) Al-Eissa, 1995).

a) Cerebrovascular accident may occur in patients with neurobrucellosis. Cerebral infarction may result from blood vessel thrombosis and spasm secondary to infectious vasculitis; intracerebral or subarachnoid hemorrhage may occur presumably secondary to ruptured mycotic aneurysm (McLean et al, 1992) Colmenero, 1996).

a) POLYRADICULOPATHY: Resembles Guillain-Barre syndrome; legs are more involved than arms. Characterized by slowly progressive flaccid paraparesis associated with backache, areflexia, sensory ataxia. Motor conduction velocities usually are normal but may show motor sensory polyneuropathy. EMG shows signs of denervation (McLean et al, 1992; Al Deeb et al, 1989) Bashir, 1985; (Shakir, 1986) 1987; Oliveri, 1996).
b) MONONEURITIS: May affect cranial nerves (Al Deeb et al, 1989). Sensorineural hearing loss secondary to involvement of the 8th cranial nerve has been reported (Shakir, 1986) Lulu, 1988; Thomas, 1993).

a) Anorexia is a common presenting symptom of acute stage, noted in up to 75% of cases (Shehabi, 1990; Lulu, 1988; (Taylor & Perdue, 1989) Mousa, 1987a; Mouaket, 1989; (Benjamin & Annobil, 1992).

a) Vomiting is a presenting symptom in 10% to 20% of cases (Revak, 1989; Al-Eissa, 1990; Lulu, 1988).

a) Weight loss may be a presenting symptom, particularly during subacute stage; incidence depends on duration of illness prior to diagnosis (Lulu, 1988; Revak, 1989; (Taylor & Perdue, 1989; Sharda & Lubani, 1986) Al-Eissa, 1990).
b) Weight loss may be rapid and substantial (Robson, 1993).

a) Abdominal pain is present in up to 1/3 of patients (Lulu, 1988; (Alvarez De Buergo et al, 1990) Yinnon, 1993; Gottesman, 1996).

a) One of the few physical signs is splenomegaly. It is present in up to 80% of patients, depending on duration of illness prior to diagnosis (Malik, 1997) Al-Eissa, 1990; Lulu, 1988; Mousa, 1988; Shehabi, 1990; (Mohd, 1989; Benjamin & Annobil, 1992). It may be accompanied by left upper quadrant tenderness (Trujillo, 1994; (Radolf, 1994) Yinnon, 1993).

a) Severe colitis presenting with abdominal pain and massive rectal bleeding has been reported in patients with brucellosis (Stermer, 1992). Colitis also may be associated with anemia in the absence of overt findings (Jorens, 1991).

a) Thrombocytopenia is an uncommon hematologic finding (6% to 14% of patients). When present, it is associated with other hematologic abnormalities, including pancytopenia (Al-Eissa, 1993a; Shalev et al, 1994).

a) Isolation of Brucella spp by culture is the gold standard for diagnosis; may not become positive for week or more (up to 6 weeks in some cases) (Chia et al, 1990) Trujillo, 1994; (Radolf, 1994); most helpful in acute B melitensis infection.
b) Brucellae grow best on trypticase, soy-based, or other enriched media. Typical doubling time is 2 hours ((Hoover, 2000)). Culture of blood, bone marrow, or other infected body fluids most reliably confirms the diagnosis. Because it is extremely infectious and there is a risk of aerosolization during initial processing of specimens, the organism should be subcultured only in a biohazard hood. Biosafety level 3 containment should be used in the laboratory when handling cultures (Staszkiewicz, 1991; Gruner, 1994; ((Hoover, 2000); CDC, 1999).

a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
b) ADVERSE EFFECTS/CONTRAINDICATIONS

a) Usual recommendation for acute (uncomplicated) brucellosis is 6 weeks of oral antibiotic, plus parenteral therapy given for first 7 to 14 days, depending on the drug (Gilbert et al, 1999; Malik, 1997) Cisneros, 1990; Acocella, 1989; (Colmenero Castillo et al, 1989) Al-Eissa, 1990).
b) Complicated cases (neurobrucellosis, endocarditis) require a minimum of 6 to 8 weeks, longer for chronic or protracted cases; may require up to 9 months of therapy (Habeeb, 1998; Akdeniz, 1998; Colmenero, 1996; Al-Eissa, 1995; (Hall, 1990).

a) INDICATIONS - Tetracyclines are most effective class of antibiotics for the treatment of brucellosis; doxycycline has largely replaced tetracycline HCl because of its longer half-life, better tissue and CNS penetration, and fewer adverse effects. Used in all combination therapies for uncomplicated and complicated cases (including neurobrucellosis) in adults and in children over 8 years (Gilbert et al, 1999; Malik, 1997) Habeeb, 1998; Akdeniz, 1998; Colmenero, 1996; Al- Eissa, 1995; (Hall, 1990).
b) DOXYCYCLINE RECOMMENDATION (Acute brucellosis) (Gilbert et al, 1999):
c) DOXYCYCLINE RECOMMENDATION (Neurobrucellosis) (Gilbert et al, 1999):

a) INDICATIONS: An aminoglycoside such as gentamicin given in combination with two or three drugs is treatment of choice for uncomplicated and complicated cases (including neurobrucellosis) in both adults and children. Many authorities have replaced streptomycin with gentamicin; gentamicin is preferred for treatment of neurobrucellosis because of better CNS penetration (Gilbert et al, 1999; Malik, 1997) Habeeb, 1998; Akdeniz, 1998; Hull, 1990; Lubani, 1989).
b) GENTAMICIN RECOMMENDATION (Uncomplicated brucellosis) (Gilbert et al, 1999):
c) GENTAMICIN RECOMMENDATION (Neurobrucellosis) (Gilbert et al, 1999) Habeeb, 1989):

a) INDICATIONS - A drug of choice, given in combination with doxycycline for treatment of uncomplicated brucellosis in adults and children over 8 years (Gilbert et al, 1999) Al-Eissa, 1990; Cisneros, 1990; Acocella, 1989; (Colmenero Castillo et al, 1989; WHO, 1986) and in combination with rifampin and either doxycycline or cotrimoxazole for neurobrucellosis in adults (Akdeniz, 1998). However, many authorities have replaced streptomycin with gentamicin, as giving IM streptomycin for an extended period makes this regimen difficult to administer in some settings; availability also may be a problem. Gentamicin is preferred for treatment of neurobrucellosis because of better CNS penetration (Hull, 1990).
b) STREPTOMYCIN RECOMMENDATION (Uncomplicated neurobrucellosis) (Gilbert et al, 1999):
c) STREPTOMYCIN RECOMMENDATION (Neurobrucellosis) (Gilbert et al, 1999):

a) INDICATIONS (UNCOMPLICATED BRUCELLOSIS) - Alternative choice, given with doxycycline for treatment of uncomplicated brucellosis in adults and children over 8 years (Gilbert et al, 1999) Cisneros, 1990; Ariza, 1985; Colmenero Castillao, 1989; Kosmidis, 1982; Shehabi, 1990; Mousa, 1987a; Acocella, 1989; (WHO, 1986) Pascual, 1988; (Hall, 1990). Rifampin plus cotrimoxazole can be used for pregnant women and patients who do not tolerate tetracyclines (Al-Eissa, 1990; Shehabi, 1990; Mousa, 1987a; (Hall, 1990; Khuri-Bulos et al, 1993).
b) INDICATIONS (NEUROBRUCELLOSIS BRUCELLOSIS) - Included in all therapeutic regimens, in combination with gentamicin and either doxycycline or cotrimoxazole, for both adults and children with neurobrucellosis (Habeeb, 1998; Akdeniz, 1998; Al-Eissa, 1995).
c) RIFAMPIN RECOMMENDATION (Uncomplicated brucellosis) (Gilbert et al, 1999):
d) RIFAMPIN RECOMMENDATION (Neurobrucellosis) (Gilbert et al, 1999) Habeeb, 1998):

a) INDICATIONS (UNCOMPLICATED BRUCELLOSIS) - Drug of choice, given with gentamicin, for use in children under 8 years; alternative, given with gentamicin, for use in adults and children over 8 years. May be associated with higher relapse rates than other antibiotics used in brucellosis (Gilbert et al, 1999; Khuri-Bulos et al, 1993) Al-Eissa, 1990; Shehabi, 1990; (Hall, 1990).
b) INDICATIONS (NEUROBRUCELLOSIS) - Has good CNS penetration. Drug of choice, given with gentamicin and rifampin, for children under 8 years; alternative, given with gentamicin and rifampin, for adults (Habeeb, 1998; l-Eissa, 1995).
c) RECOMMENDATION (Uncomplicated brucellosis) (Gilbert et al, 1999):
d) RECOMMENDATION (Neurobrucellosis) (Gilbert et al, 1999) Habeeb, 1998):

a) A prospective study was conducted to identify potential risk factors of relapse among patients (n=90) infected with brucellosis. Thirty-five (38.9%) patients received combination therapy of 2 drugs (rifampicin + cotrimoxazole or doxycycline), while 55 (61.1%) patients received a combination of 3 drugs (streptomycin + rifampicin + doxycycline). Duration of therapy ranged between 2 and 8 months. Treatment was discontinued based on both clinical improvement and seroagglutination antibody titer </= 1:80, as well as negative results for IgG and IgM antibody titers. In the group receiving two antibiotics, 60% of patients had relapse in the 2 years following completion of therapy (there was NO difference in the incidence of relapse among patients who received rifampicin + doxycycline compared to rifampicin + cotrimoxazole drug therapy). There were no cases of relapse in the patients receiving 3 drugs. In addition, in patients treated for less than 5 months the rate of relapse was 59.3%, while in patients treated for more than 5 months the rate of relapse was 7.9%. The authors suggested further studies were needed to confirm the efficacy of different regimens, and to determine which agents would best reduce relapse (El Miedany et al, 2003).

1) Fever, marked toxicity, anorexia
2) Septic shock
3) DIC
4) Neurobrucellosis with papilledema, myelitis, polyneuropathy, cranial nerve palsy
5) Chronic brucellosis with iritis

a) Steroids may also be indicated for prevention of Herxheimer-like reaction (high fever, delirium, or shock provoked by antimicrobial therapy) (Trujillo, 1994; (Radolf, 1994) Pascual, 1988).