CBRNE - Glanders and Melioidosis Medication

Limited information exists about antibiotic therapy for these conditions in humans because clinical studies examining antibiotic effectiveness in vivo are rare. For localized disease, a 60- to 150-day course of oral amoxicillin and clavulanate, doxycycline, or trimethoprim and sulfamethoxazole (TMP-SMX) may be used.

For local disease with mild toxicity, combine 2 of the 3 regimens for 30 days, then switch to monotherapy with amoxicillin and clavulanate or TMP-SMX for 60-150 days.

For extrapulmonary suppurative disease, prolong treatment for 6-12 months. Drain abscesses surgically. For severe and/or septicemic disease, initiate parenteral therapy for 2 weeks followed by oral therapy for 6 months (ceftazidime combined with TMP-SMX 8 mg TMP/kg/d and 40 mg SMX/kg/d divided qid). Add streptomycin when initiating treatment if plague cannot be excluded.

Alternative choices in severe cases of melioidosis include imipenem-cilastatin or meropenem with or without trimethoprim/sulfamethoxazole. Administration of these drugs may continue for up to 4 weeks depending on clinical response. Then, a 20-week course of doxycycline and trimethoprim/sulfamethoxazole, which is said to minimize the likelihood of relapse better than amoxicillin-clavulanic acid, is administered. The prevention of relapse in melioidosis is critical since it has been reported to occur in 23% of cases. Hence, the rational behind the prolonged therapy. Other antibiotics with activity against B pseudomallei include ceftriaxone ticarcillin-sulbactam, and aztreonam.

Currently, no proven preexposure or postexposure prophylaxis is available. Postexposure prophylaxis with TMP-SMX may be attempted. No vaccine is available for human glanders or melioidosis.

One melioidosis treatment protocol at the Royal Darwin Hospital in Australia consists of the following: ceftazidime 2 g IV q6h (50 mg/kg up to 1 g in children) for at least 14 days or meropenem 1 g IV q8h for at least 14 days (25 mg/kg up to 1 g in children) coupled with cotrimoxazole 320/1600 mg PO/IV bid for at least 14 days (8/40 mg/kg up to 320/1600 mg in children). This protocol is for moderate-to-severe manifestations and may have to be continued for more than 14 days. Once the acute episode is resolved, then the eradication period would commence.^[9]

For systemic glanders, initial therapy should consist of imipenem, ceftazidime, or meropenem plus either ciprofloxacin or doxycycline. Intravenous therapy may last as long as 2-3 weeks followed by a switch to oral antibiotics (ciprofloxacin, doxycycline, TMP/SMX, or amoxicillin/clavulanate) for up to 150 days in order to prevent reactivation (most authors believe a total of 24 weeks is advisable).^[10]

Research into the best ways to treat these diseases is still on-going. Recently, the Defense Threat Reduction Agency (DTRA), part of the Department of Defense (DoD), awarded a grant to Advanced Life Sciences to study the efficacy of cethromycin against Burkholderia pseudomallei (melioidosis) as well as other bioterror agents.^[11]

This is only one aspect in the therapeutic fight against glanders and melioidosis since it is acknowledged that these disease entities are resistant to the more traditional antimicrobial regimens. Another promising avenue of therapy is inhalational immunotherapy with cationic liposome DNA complexes (CLDC). These complexes are potent activators of innate immunity within the pulmonary system, thereby making this modality attractive in the event of an inhalational exposure to these bacteria.^[12]

Meanwhile, the search for an effective vaccine continues.^[1]

Class Summary

Base choice of antibiotic and route of administration on the clinical setting.

Meropenem (Merrem IV)

Bactericidal broad-spectrum carbapenem antibiotic that inhibits cell wall synthesis. Effective against most gram-positive and gram-negative bacteria.

Has slightly increased activity against gram-negative organisms and slightly decreased activity against staphylococci and streptococci compared with imipenem.

Imipenem and cilastatin (Primaxin)

For treatment of multiple organism infections in which other agents do not have wide spectrum coverage or are contraindicated due to potential for toxicity.

Ceftazidime (Fortaz)

Bactericidal, exerting effect by inhibition of enzymes responsible for cell wall synthesis.

Tetracycline (Minocin)

Primarily bacteriostatic and believed to exert antimicrobial effect by inhibition of protein synthesis.

Sulfamethoxazole and trimethoprim (Bactrim, Bactrim DS, Septra, Septra DS)

SMX inhibits bacterial synthesis of dihydrofolic acid by competing with PABA. TMP blocks production of tetrahydrofolic acid from dihydrofolic acid by binding to and reversibly inhibiting the required enzyme, dihydrofolate reductase; thus, it blocks 2 consecutive steps in biosynthesis of nucleic acids and proteins essential to many bacteria.

Amoxicillin and clavulanate (Augmentin)

Semisynthetic antibiotic with a broad spectrum of bactericidal activity against many gram-positive and gram-negative microorganisms. Susceptible to degradation by beta-lactamases, and, thus, spectrum of activity does not include organisms that produce these enzymes. Clavulanic acid is a beta-lactam, structurally related to penicillins, which possesses ability to inactivate a wide range of beta-lactamase enzymes commonly found in microorganisms resistant to penicillins and cephalosporins. Formulation of amoxicillin and clavulanic acid protects amoxicillin from degradation by beta-lactamase enzymes and effectively extends antibiotic spectrum of amoxicillin to include many bacteria normally resistant to amoxicillin and other beta-lactam antibiotics. Possesses properties of a broad-spectrum antibiotic and a beta-lactamase inhibitor.

Streptomycin

Aminoglycoside antibiotic recommended when less potentially hazardous therapeutic agents are ineffective or contraindicated.