Melioidosis: Clinical impact and public health threat in the tropics

Abstract

This review briefly summarizes the geographical distribution and clinical impact of melioidosis, especially in the tropics. Burkholderia pseudomallei (a gram-negative bacterium) is the major causative agent for melioidosis, which is prevalent in Singapore, Malaysia, Thailand, Vietnam, and Northern Australia. Melioidosis patients are increasingly being recognized in other parts of the world. The bacteria are intrinsically resistant to many antimicrobial agents, but prolonged treatment, especially with combinations of antibiotics, may be effective. Despite therapy, the overall case fatality rate of septicemia in melioidosis remains significantly high. Intracellular survival of the bacteria within macrophages may progress to chronic infections, and about 10% of patients suffer relapses. In the coming decades, melioidosis will increasingly afflict travelers throughout many global regions. Clinicians managing travelers returning from the subtropics or tropics with severe pneumonia or septicemia should consider acute melioidosis as a differential diagnosis. Patients with open skin wounds, diabetes, or chronic renal disease are at higher risk for melioidosis and should avoid direct contact with soil and standing water in endemic regions. Furthermore, there are fears that B. pseudomallei may be used as a biological weapon. Technological advancements in molecular diagnostics and antibiotic therapy are improving the disease outcomes in endemic areas throughout Asia. Research and development efforts on vaccine candidates against melioidosis are ongoing.

Melioidosis in lower provincial Cambodia: A case series from a prospective study of sepsis in Takeo Province

“…Accurate diagnosis is critically important in melioidosis because appropriate antimicrobial treatment varies greatly from typical empiric regimens. Burkholderia pseudomallei is intrinsically resistant to an array of antimicrobial agents, which coupled to its intracellular nature makes melioidosis extremely difficult to treat [ 22 , 53 , 54 ]. Intravenous ceftazidime or a carbapenem (imipenem or meropenem) are the mainstays of initial intensive therapy for melioidosis, as there is convincing evidence of mortality reduction compared to more standard antimicrobial agents [ 22 , 55 ].…”

Pulmonary Diseases in Refugees and Migrants in Europe

“…Serology and molecular methods are also used [22]. Localized disease may be treated with doxycycline; however, severe disease requires intravenous treatment with ceftazidime or meropenem for several weeks followed by oral consolidation with co-trimoxazole and doxycycline for up to 20 weeks [23]. Currently, there is no vaccine in clinical use; prevention is best achieved by avoiding contact with contaminated water or soil, particularly by wearing shoes [19].…”

Burkholderia pseudomallei clinical isolates are highly susceptible in vitro to cefiderocol, a novel siderophore cephalosporin

“…Treatment for B. pseudomallei infections require an “intensive” 2-8-week intravenous treatment with an antimicrobial such as a carbapenem or cephalosporin, then followed by and orally administered “eradication” treatment for 3-6 months with an antimicrobial such as trimethoprim-sulfamethoxazole 19 . Infections frequently require intensive care admission and are associated with significant morbidity 20 . This is, in part due to the intrinsic antimicrobial resistance (AMR) of B. pseudomallei , as well as acquired resistance to antimicrobials such as tetracyclines, β-lactam/β-lactamase inhibitors and rarely carbapenems 21–23 .…”

“…This is, in part due to the intrinsic antimicrobial resistance (AMR) of B. pseudomallei , as well as acquired resistance to antimicrobials such as tetracyclines, β-lactam/β-lactamase inhibitors and rarely carbapenems 21–23 . The mortality rate for patients presenting with melioidosis ranges from 10-30% in Burma, Singapore, Thailand and Vietnam 20 , while in Australia it remains approximately 10% 24 . Recent research has focused on new or repurposed compounds in order to provide improved treatment options for such infections, particularly given the potential of B. pseudomallei to be genetically manipulated or used as an agent of biologic warfare 25,26 .…”