Treatment and prognosis of melioidosis
- Bart Currie, MBBS, FRACP
Bart Currie, MBBS, FRACP
- Infectious Diseases Physician
- Royal Darwin Hospital and Menzies School of Health Research
- Nicholas M Anstey, MBBS, FRACP, PhD
Nicholas M Anstey, MBBS, FRACP, PhD
- Infectious Diseases Physician
- Royal Darwin Hospital and Menzies School of Health Research
Melioidosis is a clinically diverse disease caused by the facultative intracellular gram-negative bacterium, Burkholderia pseudomallei [1-3]. This organism is a widely distributed environmental saprophyte in soil and fresh surface water in endemic regions ; the risk of acquiring the infection occurs in these same areas.
The treatment and prognosis of melioidosis will be presented here. The epidemiology, pathogenesis, clinical manifestations, and diagnosis of melioidosis are discussed separately. (See "Epidemiology, clinical manifestations, and diagnosis of melioidosis".)
All cases of melioidosis, even mild disease, should be treated with initial intensive therapy (at least two weeks of intravenous therapy) followed by eradication therapy orally for a minimum of three months. B. pseudomallei are characteristically resistant to penicillin, ampicillin, first- and second-generation cephalosporins, gentamicin, tobramycin, and streptomycin [5-7].
Initial intensive therapy — We recommend intensive therapy with one of the following regimens:
●Ceftazidime (50 mg/kg up to 2 g IV every six hours)To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- White NJ. Melioidosis. Lancet 2003; 361:1715.
- Currie BJ. Melioidosis: an important cause of pneumonia in residents of and travellers returned from endemic regions. Eur Respir J 2003; 22:542.
- Wiersinga WJ, Currie BJ, Peacock SJ. Melioidosis. N Engl J Med 2012; 367:1035.
- Dance DA. Ecology of Burkholderia pseudomallei and the interactions between environmental Burkholderia spp. and human-animal hosts. Acta Trop 2000; 74:159.
- Leelarasamee A, Bovornkitti S. Melioidosis: review and update. Rev Infect Dis 1989; 11:413.
- Eickhoff TC, Bennett JV, Hayes PS, Feeley J. Pseudomonas pseudomallei: susceptibility to chemotherapeutic agents. J Infect Dis 1970; 121:95.
- Chaowagul W. Recent advances in the treatment of severe melioidosis. Acta Trop 2000; 74:133.
- White NJ, Dance DA, Chaowagul W, et al. Halving of mortality of severe melioidosis by ceftazidime. Lancet 1989; 2:697.
- Currie BJ, Fisher DA, Howard DM, et al. Endemic melioidosis in tropical northern Australia: a 10-year prospective study and review of the literature. Clin Infect Dis 2000; 31:981.
- Cheng AC, Lowe M, Stephens DP, Currie BJ. Ethical problems of evaluating a new treatment for melioidosis. BMJ 2003; 327:1280.
- Cheng AC, Stephens DP, Anstey NM, Currie BJ. Adjunctive granulocyte colony-stimulating factor for treatment of septic shock due to melioidosis. Clin Infect Dis 2004; 38:32.
- Sookpranee M, Boonma P, Susaengrat W, et al. Multicenter prospective randomized trial comparing ceftazidime plus co-trimoxazole with chloramphenicol plus doxycycline and co-trimoxazole for treatment of severe melioidosis. Antimicrob Agents Chemother 1992; 36:158.
- Huffam S, Jacups SP, Kittler P, Currie BJ. Out of hospital treatment of patients with melioidosis using ceftazidime in 24 h elastomeric infusors, via peripherally inserted central catheters. Trop Med Int Health 2004; 9:715.
- Walsh AL, Smith MD, Wuthiekanun V, White NJ. Postantibiotic effects and Burkholderia (Pseudomonas) pseudomallei: evaluation of current treatment. Antimicrob Agents Chemother 1995; 39:2356.
- Dance DA, Wuthiekanun V, Chaowagul W, White NJ. The antimicrobial susceptibility of Pseudomonas pseudomallei. Emergence of resistance in vitro and during treatment. J Antimicrob Chemother 1989; 24:295.
- Smith MD, Wuthiekanun V, Walsh AL, White NJ. Susceptibility of Pseudomonas pseudomallei to some newer beta-lactam antibiotics and antibiotic combinations using time-kill studies. J Antimicrob Chemother 1994; 33:145.
- Ashdown LR. In vitro activities of the newer beta-lactam and quinolone antimicrobial agents against Pseudomonas pseudomallei. Antimicrob Agents Chemother 1988; 32:1435.
- McEniry DW, Gillespie SH, Felmingham D. Susceptibility of Pseudomonas pseudomallei to new beta-lactam and aminoglycoside antibiotics. J Antimicrob Chemother 1988; 21:171.
- Yamamoto T, Naigowit P, Dejsirilert S, et al. In vitro susceptibilities of Pseudomonas pseudomallei to 27 antimicrobial agents. Antimicrob Agents Chemother 1990; 34:2027.
- Smith MD, Wuthiekanun V, Walsh AL, White NJ. In-vitro activity of carbapenem antibiotics against beta-lactam susceptible and resistant strains of Burkholderia pseudomallei. J Antimicrob Chemother 1996; 37:611.
- Simpson AJ, Suputtamongkol Y, Smith MD, et al. Comparison of imipenem and ceftazidime as therapy for severe melioidosis. Clin Infect Dis 1999; 29:381.
- Cheng AC, Fisher DA, Anstey NM, et al. Outcomes of patients with melioidosis treated with meropenem. Antimicrob Agents Chemother 2004; 48:1763.
- Cheng AC, McBryde ES, Wuthiekanun V, et al. Dosing regimens of cotrimoxazole (trimethoprim-sulfamethoxazole) for melioidosis. Antimicrob Agents Chemother 2009; 53:4193.
- Jenney AW, Lum G, Fisher DA, Currie BJ. Antibiotic susceptibility of Burkholderia pseudomallei from tropical northern Australia and implications for therapy of melioidosis. Int J Antimicrob Agents 2001; 17:109.
- Dance DA, Wuthiekanun V, White NJ, Chaowagul W. Antibiotic resistance in Pseudomonas pseudomallei. Lancet 1988; 1:994.
- Godfrey AJ, Wong S, Dance DA, et al. Pseudomonas pseudomallei resistance to beta-lactam antibiotics due to alterations in the chromosomally encoded beta-lactamase. Antimicrob Agents Chemother 1991; 35:1635.
- Dance DA, Wuthiekanun V, Chaowagul W, et al. Development of resistance to ceftazidime and co-amoxiclav in Pseudomonas pseudomallei. J Antimicrob Chemother 1991; 28:321.
- Toohey M, Lew AE, Desmarchelier PM. Laboratory investigations of Australian isolates of ceftazidime resistant Pseudomonas pseudomallei. Antibiotic Special Interest Group (Australian Society of Microbiology) Newsletter 1994; 2:1.
- Dance DA, Wuthiekanun V, Chaowagul W, White NJ. Interactions in vitro between agents used to treat melioidosis. J Antimicrob Chemother 1989; 24:311.
- Chierakul W, Anunnatsiri S, Short JM, et al. Two randomized controlled trials of ceftazidime alone versus ceftazidime in combination with trimethoprim-sulfamethoxazole for the treatment of severe melioidosis. Clin Infect Dis 2005; 41:1105.
- Chierakul W, Anunnatsiri S, Chaowagul W, et al. Addition of trimethoprim-sulfamethoxazole to ceftazidime during parenteral treatment of melioidosis is not associated with a long-term outcome benefit. Clin Infect Dis 2007; 45:521.
- Thamprajamchit S, Chetchotisakd P, Thinkhamrop B. Cefoperazone/sulbactam + co-trimoxazole vs ceftazidime + co-trimoxazole in the treatment of severe melioidosis: a randomized, double-blind, controlled study. J Med Assoc Thai 1998; 81:265.
- Suputtamongkol Y, Rajchanuwong A, Chaowagul W, et al. Ceftazidime vs. amoxicillin/clavulanate in the treatment of severe melioidosis. Clin Infect Dis 1994; 19:846.
- Dance D. Treatment and prophylaxis of melioidosis. Int J Antimicrob Agents 2014; 43:310.
- Writing Group: Melioidosis. In: Therapeutic Guidelines: Antibiotic, 15th ed, Therapeutic Guidelines Ltd, North Melbourne, 2014.
- Pitman MC, Luck T, Marshall CS, et al. Intravenous therapy duration and outcomes in melioidosis: a new treatment paradigm. PLoS Negl Trop Dis 2015; 9:e0003586.
- Currie BJ. Melioidosis: evolving concepts in epidemiology, pathogenesis, and treatment. Semin Respir Crit Care Med 2015; 36:111.
- Demar M, Ferroni A, Dupont B, et al. Suppurative epididymo-orchitis and chronic prostatitis caused by Burkholderia pseudomallei: a case report and review. J Travel Med 2005; 12:108.
- Morse LP, Moller CC, Harvey E, et al. Prostatic abscess due to Burkholderia pseudomallei: 81 cases from a 19-year prospective melioidosis study. J Urol 2009; 182:542.
- Low JG, Quek AM, Sin YK, Ang BS. Mycotic aneurysm due to Burkholderia pseudomallei infection: case reports and literature review. Clin Infect Dis 2005; 40:193.
- Amezyane T, Lecoules S, Algayres JP. Mycotic iliac aneurysm associated with Burkholderia pseudomallei. Int J Infect Dis 2010; 14 Suppl 3:e381.
- Cheng AC, Limmathurotsakul D, Chierakul W, et al. A randomized controlled trial of granulocyte colony-stimulating factor for the treatment of severe sepsis due to melioidosis in Thailand. Clin Infect Dis 2007; 45:308.
- Dance DA, Davong V, Soeng S, et al. Trimethoprim/sulfamethoxazole resistance in Burkholderia pseudomallei. Int J Antimicrob Agents 2014; 44:368.
- Crowe A, McMahon N, Currie BJ, Baird RW. Current antimicrobial susceptibility of first-episode melioidosis Burkholderia pseudomallei isolates from the Northern Territory, Australia. Int J Antimicrob Agents 2014; 44:160.
- Saiprom N, Amornchai P, Wuthiekanun V, et al. Trimethoprim/sulfamethoxazole resistance in clinical isolates of Burkholderia pseudomallei from Thailand. Int J Antimicrob Agents 2015; 45:557.
- Chetchotisakd P, Chierakul W, Chaowagul W, et al. Trimethoprim-sulfamethoxazole versus trimethoprim-sulfamethoxazole plus doxycycline as oral eradicative treatment for melioidosis (MERTH): a multicentre, double-blind, non-inferiority, randomised controlled trial. Lancet 2014; 383:807.
- Chaowagul W, Simpson AJ, Suputtamongkol Y, et al. A comparison of chloramphenicol, trimethoprim-sulfamethoxazole, and doxycycline with doxycycline alone as maintenance therapy for melioidosis. Clin Infect Dis 1999; 29:375.
- Currie BJ, Fisher DA, Anstey NM, Jacups SP. Melioidosis: acute and chronic disease, relapse and re-activation. Trans R Soc Trop Med Hyg 2000; 94:301.
- Chaowagul W, Chierakul W, Simpson AJ, et al. Open-label randomized trial of oral trimethoprim-sulfamethoxazole, doxycycline, and chloramphenicol compared with trimethoprim-sulfamethoxazole and doxycycline for maintenance therapy of melioidosis. Antimicrob Agents Chemother 2005; 49:4020.
- Rajchanuvong A, Chaowagul W, Suputtamongkol Y, et al. A prospective comparison of co-amoxiclav and the combination of chloramphenicol, doxycycline, and co-trimoxazole for the oral maintenance treatment of melioidosis. Trans R Soc Trop Med Hyg 1995; 89:546.
- Chaowagul W, Suputtamongkul Y, Smith MD, White NJ. Oral fluoroquinolones for maintenance treatment of melioidosis. Trans R Soc Trop Med Hyg 1997; 91:599.
- Chetchotisakd P, Chaowagul W, Mootsikapun P, et al. Maintenance therapy of melioidosis with ciprofloxacin plus azithromycin compared with cotrimoxazole plus doxycycline. Am J Trop Med Hyg 2001; 64:24.
- Ashdown LR, Currie BJ. Melioidosis: when in doubt leave the quinolone alone! Med J Aust 1992; 157:427.
- Cheng AC, Chierakul W, Chaowagul W, et al. Consensus guidelines for dosing of amoxicillin-clavulanate in melioidosis. Am J Trop Med Hyg 2008; 78:208.
- Chau PY, Ng WS, Leung YK, Lolekha S. In vitro susceptibility of strains of Pseudomonas pseudomallei isolated in Thailand and Hong Kong to some newer beta-lactam antibiotics and quinolone derivatives. J Infect Dis 1986; 153:167.
- Desmarchelier PM, Dance DA, Chaowagul W, et al. Relationships among Pseudomonas pseudomallei isolates from patients with recurrent melioidosis. J Clin Microbiol 1993; 31:1592.
- Chaowagul W, Suputtamongkol Y, Dance DA, et al. Relapse in melioidosis: incidence and risk factors. J Infect Dis 1993; 168:1181.
- Haase A, Melder A, Smith-Vaughan H, et al. RAPD analysis of isolates of Burkholderia pseudomallei from patients with recurrent melioidosis. Epidemiol Infect 1995; 115:115.
- Mohandas S, Puthucheary S, Pang T. Relapsing infection due to Burkholderia pseudomallei detected by pulsed-field gel electrophoresis of sequential clinical isolates. Asian Pac J Mol Biol 1995; 3:224.
- Limmathurotsakul D, Chaowagul W, Chierakul W, et al. Risk factors for recurrent melioidosis in northeast Thailand. Clin Infect Dis 2006; 43:979.
- Sarovich DS, Ward L, Price EP, et al. Recurrent melioidosis in the Darwin Prospective Melioidosis Study: improving therapies mean that relapse cases are now rare. J Clin Microbiol 2014; 52:650.
- Suputtamongkol Y, Dance DA, Chaowagul W, et al. Amoxycillin-clavulanic acid treatment of melioidosis. Trans R Soc Trop Med Hyg 1991; 85:672.
- Cheng AC, West TE, Limmathurotsakul D, Peacock SJ. Strategies to reduce mortality from bacterial sepsis in adults in developing countries. PLoS Med 2008; 5:e175.
- Currie BJ, Ward L, Cheng AC. The epidemiology and clinical spectrum of melioidosis: 540 cases from the 20 year Darwin prospective study. PLoS Negl Trop Dis 2010; 4:e900.
- Currie BJ, Fisher DA, Howard DM, Burrow JN. Neurological melioidosis. Acta Trop 2000; 74:145.
- Initial intensive therapy
- - Ceftazidime
- - Carbapenems
- - Addition of TMP-SMX during initial intensive therapy
- - Alternative agents
- - Duration of intensive therapy
- Adjunctive therapy in the intensive phase
- - Abscess drainage
- - Recombinant G-CSF
- Subsequent eradication therapy
- - Choice of agents
- - Duration
- RISK OF RELAPSE
- SUMMARY AND RECOMMENDATIONS