Activities of five new fluoroquinolones against Pseudomonas pseudomallei

Abstract

Thirty-four isolates of Pseudomonas pseudomallei were tested by a broth microdilution technique for susceptibility to amifloxacin, ciprofloxacin, enoxacin, norfloxacin, and ofloxacin. Ciprofloxacin was the most active agent tested, with an MIC for 90% of the strainis tested of 8 ,ug/Iml. These in vitro results suggest that the fluoroquinolones tested would not be optimal for therapy of melioidosis.The new quinolones have marked activity against aerobic gram-negative rods, including many strains of Pseudomonas aeruginosa (4). Because Pseudomonas pseudomallei, the causative agent of melioidosis, is an important pathogen in certain parts of the world, and the current therapeutic armamentarium is limited, it would be desirable to find an additional effective agent against this pathogen (3,5). In reviewing the literature we found little information on the activity of the newer quinolones against P. pseudomallei. Therefore, we tested the susceptibilities of 34 isolates of P. pseudomallei to five fluoroquinolones in order to determine their possible role in the therapy of melioidosis.Thirty-four isolates of P. pseudomallei were provided from material collected by Richard A. Finkelstein. The strains were obtained from environmental sources in Thailand and from U.S. Armed Forces patients in Vietnam. The strains had previously been identified and had been stored in a lyophilized state for several years. All strains were reconstituted from the lyophilized state and harvested. They were frozen until needed and then grown in Mueller-Hinton broth, and an overnight growth of log-phase bacteria was used for inoculation. Escherichia coli ATCC 25922 and P. aeruginosa ATCC 27853 were used as control strains.Antimicrobial The results of the broth dilution susceptibility tests are shown in Table 1. Ciprofloxacin was the most active quinolone tested against all strains of P. pseudomallei. Current recommendations provided by the manufacturers suggest a cutoff value of 1 ,ug/ml for gram-negative rods to be considered susceptible to amifloxacin, ciprofloxacin, and ofloxacin and a cutoff value of 2 ,ug/ml for enoxacin and norfloxacin. As noted, all MICs for 90% of the strains tested exceeded these limits.The quinolones are potent antimicrobial agents for many pathogens. They provide an attractive oral therapeutic alternative to intravenous therapy in many situations. Because of their potency, ease of administration, low development of in vitro resistance, and low toxicity, they would be an appealing alternative to standard therapy in melioidosis.The current study demonstrated that the MICs of the quinolones for 34 strains of P. pseudomallei were lower than commonly achievable concentrations in serum of the five agents tested (2, 4). Ciprofloxacin was the most effective agent, with an MIC for 90% of the strains tested of 8 ,ug/ml. The results of our work are in agreement with those of Chau et al.(1). They tested the susceptibilities of 27 isolates of P. pseuidomallei to a number of antimicrobial agents, including two quinolones, ciproflox...

Pseudomonas pseudomallei, a common pathogen in Thailand that is resistant to the bactericidal effects of many antibiotics

“…The new broad-spectrum quinolone antibiotics penetrate phagocytes well (32). In general, however, they have shown limited activity against P. pseudomallei in vitro (2,6,8,20,33,34 (22). The P-lactamase-producing strains in our study which were highly resistant to ticarcillin-clavulanate also had relatively high imipenem MICs (4 ,ug/ml).…”

In vitro susceptibilities of Pseudomonas pseudomallei to 27 antimicrobial agents

“…Several antimicrobial agents in the groups of newer quinolones, broad-spectrum cephems, carbapenems, monobactams, penicillins, and (2,4,16,20). We showed here that some additional antimicrobial agents have good in vitro activity against P. pseudomallei and that the incidence of drug-resistant isolates is still extremely low with P. pseudomallei.…”

Present and future therapeutic strategies for melioidosis and glanders

“…However, the ability of quinolones, and newer fluoroquinolones in particular, to accumulate within phagocytes suggests they may still prove useful for the treatment of melioidosis. Although widely tested in vitro [30,51,52] and, to a lesser extent, in vivo [53] in a murine melioidosis model, the fluoroquinolones have poor clinical efficacy and are currently not recommended for the treatment of melioidosis [50,54]. A comparison of ciprofloxacin and azithromycin for 12 weeks versus trimethoprim–sulfamethoxazole and doxycycline for 20 weeks demonstrated a relapse rate of 22 and 3%, respectively, in clinical studies [33].…”