In Vitro Susceptibility of Ceftolozane-Tazobactam against Burkholderia pseudomallei

LETTER

Burkholderia pseudomallei is the cause of melioidosis, a potentially serious and fatal disease characterized by community-acquired pneumonia and/or sepsis found mainly in Southeast Asia and northern Australia, and high case fatality rates of up to 19% are observed in areas where the disease is endemic (1). In recent years, the disease has been increasingly reported in countries outside the Asia-Pacific region, including India, Mauritius, South, Central, and North America, and West and East Africa. Treatment of B. pseudomallei infection often requires the use of amoxicillin-clavulanic acid, ceftazidime, piperacillin-tazobactam, and the carbapenems, but resistance to these antibiotics by B. pseudomallei is commonly observed. Owing to its high mortality rates, antibiotic resistance, and possible transmission by aerosols, B. pseudomallei is considered a potential agent of biological warfare and has been classified as a category B bioterrorism agent by the Centers for Disease Control and Prevention (Atlanta, GA, USA; https://emergency.cdc.gov/agent/agentlist-category.asp). In addition to causing human diseases, B. pseudomallei is an important cause of fatal infection in captive marine mammals and birds, including bottlenose dolphins, California sea lions, pilot whales, and zebra doves.

Ceftolozane-tazobactam is a cephalosporin–β-lactamase inhibitor combination recently launched on the market. Based on the results from its in vitro susceptibility spectrum and preliminary clinical experience, it is particularly useful for the treatment of infections associated with extended-spectrum-β-lactamase-producing Enterobacteriaceae and carbapenem-resistant Pseudomonas aeruginosa (2). Recently, Mazer et al. described the in vitro susceptibilities of Burkholderia cepacia complex organisms and Burkholderia gladioli to ceftolozane-tazobactam and other antibiotics and found that 77% of the strains were susceptible to ceftolozane-tazobactam (3). We hypothesized that a significant proportion of B. pseudomallei strains may also be susceptible to ceftolozane-tazobactam. Here, we report the in vitro susceptibility to ceftolozane-tazobactam of B. pseudomallei.

We examined the MICs of ceftolozane-tazobactam for 62 strains of B. pseudomallei using the Etest (Liofilchem). Strains were collected from patients with melioidosis (32 strains), marine mammals (16 strains) and birds (10 strains) with melioidosis in an oceanarium, and soil samples in Hong Kong (4 strains) (4, 5). Quality control strains Staphylococcus aureus ATCC 29213 and Pseudomonas aeruginosa ATCC 27853 were used as reference strains for the Etest. Results were interpreted based on CLSI standards for non-Enterobacteriaceae. Of the 62 B. pseudomallei strains tested, 90.6% of the patient strains and 100% of the animal and environmental strains were inhibited by concentrations of ≤4 μg/ml ceftolozane-tazobactam, demonstrating good overall activity of the drug against B. pseudomallei (Table 1).

TABLE 1.

Activities of ceftolozane-tazobactam against Burkholderia pseudomallei strains

Source (no. of strains)	MIC range (μg/ml)	No. (%) of strains susceptiblea
Patients (32)	1.5 to ≥256	29 (90.6)
Marine mammals (16)	1.5 to 4	16 (100)
Birds (10)	1.5 to 4	10 (100)
Environment (4)	1.5 to 3	4 (100)

^aInterpretations of results were based on CLSI standards for non-Enterobacteriaceae.

Ceftolozane-tazobactam is an alternative antibiotic for the treatment of B. pseudomallei infection. As Burkholderia species are often resistant to multiple antibiotics, it is of crucial importance to look for alternative choices, in particular, new antibiotics on the horizon, for the treatment of infections associated with this genus of bacteria. The present results and the previous study by Mazer et al. (3) showed that a high proportion of B. pseudomallei, B. cepacia complex, and B. gladioli strains were susceptible to ceftolozane-tazobactam. In particular, >90% of the B. pseudomallei clinical strains isolated from patients and animals were susceptible to ceftolozane-tazobactam, making it a potentially important choice in the armamentarium for the treatment of melioidosis.