In vitro antimicrobial activity of cefodizime, a third generation cephalosporin.

Cefodizime is one of the new broad-spectrum cephalosporins. It is an aminothiazolyl iminomethoxy cephalosporin which is metabolically stable and has a prolonged serum half life. Cefodizime was primarily active against gram-negative bacilli and at the concentration of 0.5 mg/L, it inhibited 90 per cent of Enterobacteriaceae. P. mirabilis was the most susceptible species tested (MIC90 of 0.02 mg/L). E.coli, K.pneumoniae, Salmonella spp., Shigella spp. and M. morganii were also very sensitive to cefodizime, with the MIC90 of 0.25-0.5 mg/L. Cefodizime, however, was not active against most gram-negative bacilli possessing Type I beta-lactamases of Richmond and Sykes, namely, Enterobacter spp., P. aeruginosa and A. anitratus (MIC90 of > 128 mg/L). Among gram-positive bacteria, only S.pyogenes was highly susceptible (MIC90 of 0.05 mg/L), while S. aureus (methicillin-sensitive) was moderately susceptible and Enterococcus spp. was resistant. Cefodizime appeared to be bactericidal and was not affected by serum. High inoculum (10(7) cfu/ml) of K.pneumoniae and Enterobacter spp. resulted in increase of the MIC of cefodizime. This study shows that local bacterial isolates in a university hospital in Bangkok, Thailand were not different in susceptibility pattern from those reported in developed countries. The in vitro activity of cefodizime as a third generation cephalosporin, with its good pharmacokinetic property, and the property of the agent as a biological response modifier, should prove that this is a promising new agent in treating serious infections especially in immunosuppressed hosts.

Ciprofloxacin in severe infections.

Ciprofloxacin is the most potent post-marketing fluoroquinolone. In vitro activity and pharmacokinetic properties of this agent, together with clinical trials of the drug may be very promising in the treatment of severe infections, especially when the bacteria involved are resistant to other conventional agents. We performed an open clinical trial of this agent in hospitalized patients with severe infections in a university hospital in Bangkok, Thailand. A total of 25 patients were enrolled on the basis of clinical diagnosis of severe bacterial infections. Six of these patients were dropouts (3 of which proved to be non-bacterial infections, 2 patients each had only anaerobic infection and nocardiosis. One suffered from a severe psychotic attack). The remaining 19 patients were evaluated. There were 12 males and 7 females, the age ranged from 13 to 77 years old (43.2 +/- 20.1). Most had severe underlying illnesses (17 out of 19). There were 23 infections in 19 patients. Septicemia was the most common infection treated. Other infections included complicated urinary infection, upper respiratory tract infection, skin/skin structure infection. P. aeruginosa was the most common pathogen infected. Other organisms were E.coli, Enterobacter, P.mirabilis, S.aureus, A.antitratus and mycobacterium. Ciprofloxacin was given as an initial 100 mg twice daily as intravenous infusion, and this was switched to an oral form of 500 mg b.i.d./at approximately day 4 to day 6. The overall cure rate was 68 per cent. There were 2 improvements, 2 relapses/reinfections and one failure. Toxic effect included one psychotic attack necessitating discontinuation of the drug. Other adverse drug reactions were mild and transient. These included elevation of transaminase and LDH.(ABSTRACT TRUNCATED AT 250 WORDS)

In vitro activities of antimicrobial combination against Pseudomonas pseudomallei.

P pseudomallei infection was treated empirically with an antimicrobial combination without hard evidence of a more favorable outcome over single drug regimens. The so-called "conventional' agents, namely kanamycin (K), chloramphenicol (C), doxycycline (D) and sulfamethoxazole/trimethoprim (SMZ/TMP) are often combined. We determined the effects of the combination of these agents by standard time-kill curve. Six combinations were tested, i.e. K and C, K and D, K and SMZ/TMP, C and D, C and SMZ/TMP, and lastly, D and SMZ/TMP. Three recent clinical isolates of P. pseudomallei were used. The antimicrobial concentration in the combination selected was one-fourth of the minimal inhibiting concentration (MIC). Colony counts were performed at times 0, 2, 4, 6 and 24 hours. The results were interpreted using standard definition, as synergistic, additive and antagonistic effects. It was found that at time 0 to 6 hours, all of the combinations only acted additively. At 24 hours, however, there were 3 effects observed. These were (1) synergistic effects for K and D, and C and D; (2) additive effect for K and C, K and SMZ/TMP, and D and SMZ/TMP; and (3) antagonistic effect for C and SMZ/TMP. None of the combinations showed rapid killing rates. The results, although subjected to precautious extrapolation of in vitro to in vivo situations, suggested that the combined regimens of "conventional' drugs often acted additively, and none of these combinations offered fast killing.