Bacteriologic and Pharmacodynamic Aspects of Nalidixic Acid

Cinoxacin was almost completely absorbed when given orally and was found to be approximately 60 to 70% protein bound. Peak serum concentrations were reached within 2 h, and detectable serum concentrations persisted up to 12 h after administration of 0.25-, 0.5-, and 1-g multiple oral doses. Although food delayed the absorption and caused a 30% reduction in mean peak serum concentrations, the overall 24-h urinary recovery was not significantly altered. Approximately 50 to 55% of the drug was excreted in the urine as unchanged drug. At 12 h, urine concentrations were still above the minimal inhibitory concentration for most common gram-negative urinary pathogens. Cinoxacin was well tolerated when administered to 23 volunteers from 10 to 28 days. Resistance among fecal isolates initially susceptible to cinoxacin was not observed in nine volunteers who were administered 0.5 g every 12 h for 4 to 28 days.

Section: Resultssupporting

confidence: 75%

Pharmacology of Cinoxacin in Humans

Black

Israel

Wolen

et al. 1979

“…However, there has been controversy in the literature regarding the value of susceptibility testing of NA in predicting the outcome of therapy. Some investigators have reported rapid emergence of resistant bacterial mutants and development of resistant superinfections during NA therapy (7,16,25), whereas others have reported a lesser degree of bacterial resistance with good success in the treatment of UTI (4,28,29,34 After therapy, the fecal flora showed that the emergence of resistant strains to NA (1.1%) and TMP/SMZ (2.3%) was minimal as compared with other antibiotics (12,28). This finding was consistent with the low incidence of resistant isolates in the follow-up urine cultures.…”

Section: Methodsmentioning

confidence: 99%

Comparative efficacy and safety of nalidixic acid versus trimethoprim/sulfamethoxazole in treatment of acute urinary tract infections in college-age women

Iravani¹,

Richard²,

Baer³

et al. 1981

One hundred and thirty-five college-age women with acute urinary tract infections caused by gram-negative Enterobacteriaceae were treated by random allocation with either nalidixic acid (NA), 1 g every 6 h for 7 days, or trimethoprim/sulfamethoxazole (TMP/SMZ), 160/800 mg every 12 h for 10 (5,10,22). Nalidixic acid (NA) has a broad spectrum of activity against gram-negative Enterobacteriaceae. Pseudomonas species and gram-positive cocci are resistant to this agent (6,23,24). Oral doses of both drugs produce bactericidal urinary levels well in excess of the miniimal inhibitory concentration for most urinary pathogens (20). TMP/SMZ is considered an effective drug for the treatment of urinary tract infections (UTIs) (5,9,13,21,28,35). However, because of conflicting reports and controversy over the emergence of bacterial resistance, NA has been used less frequently (8,25,28).In this study, the efficacy of NA was compared with that of TMP/SMZ for treatment of acute UTIs in young women. The antibody-coated bacteria test (ACBT) was used to localize the site of the infections (32, 33). Criteria were established to allow recurrences to be subdivided into reinfections and relapses. The effects of these drugs on the ecology of the fecal flora, as well as the emergence of resistant urinary pathogens, were assessed. MATERIALS AND METHODSThe patient population was comprised of college women who entered the University of Florida Outpatient Clinic with symptoms of acute UTI. The criterion for inclusion in the study was the presence of more than 105 colonies of the same gram-negative Enterobacteriaceae per ml in each of three consecutive urine samples obtained within 24 h of initiating therapy. Lower urinary tract symptoms were monitored by the use of a patient diary. The time of each voiding and the degree of severity of each symptom were recorded in the diary during the first 3 days of therapy. Women with asymptomatic infections were included in the study. They were identified from a group of students who were having monthly urine cultures done as follow-up for previous UTIs. Patients

“…These acids are structurally related to nalidixic acid (NAL) and oxolinic acid (OA), which are well-known agents against gram-negative organisms (1)(2)(3)(4)(5)(6)(7). A preliminary bacteriological test showed that 7-ethyl-2-methyl-4-oxo-4,7-dihydrothieno (2,3-b) pyridine-5-carboxylic acid (I) (Fig.…”

mentioning

confidence: 99%

Comparative in vitro studies of nalidixic acid, oxolinic acid, and a new analog with thieno (2,3-b) pyridine structure

Gilis¹,

Haemers²,

Pattyn³

1978

Bacterial susceptibility to a new organic acid related to nalidixic acid and oxolinic acid was tested. The in vitro susceptibility pattem of the new compound was found to be very similar to that of nalidixic acid.In our laboratory we synthesized a series of 4-oxo-4,7-dihydrothieno (2,3-b) pyridine-5-carboxylic acids. These acids are structurally related to nalidixic acid (NAL) and oxolinic acid (OA), which are well-known agents against gram-negative organisms (1-7). A preliminary bacteriological test showed that 7-ethyl-2-methyl-4-oxo-4,7-dihydrothieno (2,3-b) pyridine-5-carboxylic acid (I) (Fig. 1) was the most promising compound of the series. The present study evaluates the in vitro susceptibility of different organisms to this new compound and to NAL and OA as well as the potential for development ofbacterial resistance to these drugs.The following 60 organisms were used in this study: 9 strains of Pseudomonas aeruginosa, 4 Klebsiella pneumoniae, 2 Proteus morganii, 2 Proteus rettgeri, 4 Staphylococcus aureus, 6 Enterococci, 2 Serratia marcescens, and 31 Escherichia coli. All strains, except one E. coli (ATCC 25922), were isolates from a clinical laboratory (Institute for Tropical Medicine, Antwerp).Antibacterial activity was determined with the agar-dilution method in Mueller-Hinton agar. Twofold dilutions in water of stock solutions, containing 2,000 jig of the drugs per ml of 0.1 N NaOH, were added to the medium to obtain a final concentration range from 128 to 0.25 ,tg of drug per ml. A replicating device (8) was used. Overnight cultures of the bacteria to be tested were diluted so that the inocula contained 104 colony-forming units. The minimal inhibitory concentration (MIC) was defined as the lowest concentration of antibacterial agent allowing the growth ofno more than five colonies at the site of inoculation after overnight incubation at 370C.Results are represented in Table 1. Proteus sp. and E. coli were the most susceptible species, with a mean MIC of 1 and 2 ug/ml, respectively, for both I and NAL, and 0.25 jug/ml for OA. One strain of E. coli was resistant to both I and NAL (MIC > 128 ,ug/ml), with a MIC of 2 lag of OA per ml. All gram-positive strains and Pseudomonas aeruginosa were resistant to 64 ,ug of I or NAL per ml. All Enterococci strains were resistant to I and NAL. In general, the MICs of I and NAL were similar. However, certain differences were noted. For instance, Serratia marcescens strains were inhibited by 64 ug of I per ml, whereas they were resistant to more than 128 ,ug of NAL per ml. Otherwise, some of the Kleb-FIG. 1. Chemical structure ofI (7-ethyl-2-methyl-4-oxo-4,7-dihydrothieno (2,3-b) pyridine-5-carboxylic acid). siella sp. were more susceptible to NAL than to I. Without exception, the MICs of OA were lower than those of I or NAL. One K. pneumoniae strain was resistant to both I and NAL (MIC > 128 ,ug/ml); the MIC of OA was 64 itg/ml.