Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1996). I. Susceptibility distribution

The frequencies of isolation and susceptibilities to antimicrobial agents were investigated on 680 bacterial strains isolated from patients with urinary tract infections (UTIs) in 10 hospitals during the period of June 1996 to May 1997. Of the above bacterial isolates, Gram-positive bacteria accounted for 30.4% and a majority of them were Enterococcus faecalis. Gram-negative bacteria accounted for 69.6% and most of them were Escherichia coli. Susceptabilities of several isolated bacteria to antimicrobial agents were as followed; 1. Enterococcus faecalis Ampicillin (ABPC) showed the highest activity against E. faecalis isolated from patients with UTIs. Its MIC90 was 1 microgram/ml. Imipenem (IPM) and vancomycin (VCM) were also active with the MIC90S of 2 micrograms/ml. The others had low activities with the MIC90S of 16 micrograms/ml or above. 2. Staphylococcus aureus including MRSA Arbekacin (ABK) and VCM showed the highest activities against both S. aureus and MRSA isolated from patients with UTIs. The MIC90S of them were 1 or 2 micrograms/ml. The others except minocycline (MINO) had low activities with the MIC90S of 32 micrograms/ml or above. 3. Staphylococcus epidermidis ABK and VCM showed the strongest activities against S. epidermis isolated from patients with UTIs. The MICs for all strains were equal to or lower than 2 micrograms/ml. Cefazolin (CEZ), cefotiam (CTM) and cefozopran (CZOP) were also active with the MIC90S of 4 micrograms/ml. Compared with antimicrobial activities of cephems is 1995, the MIC90S of them had changed into a better state. They ranged from 4 micrograms/ml 16 micrograms/ml in 1996. 4. Streptococcus agalactiae All drugs except MINO were active against S. agalactiae. ABPC, CZOP, IPM, and clarithromycin (CAM) showed the highest activities. The MICs for all strains were equal to or lower than 0.125 micromilligrams. Tosufloxacin (TFLX) and VCM were also active with the MIC90S of 0.5 micromilligrams. 5. Citrobacter freundii Gentamicin (GM) showed the highest activity against C. freundii isolated from patients with UTIs. Its MIC90 was 0.5 micrograms/ml. IPM and amikacin (AMK) were also active with the MIC90S of 1 microgram/ml and 2 micrograms/ml, respectively. Cefpirome (CPR) and CZOP were also active with the MIC90S of 8 micrograms/ml. The MIC90S of the others were 16 micrograms/ml or above. 6. Enterobacter cloacae IPM showed the highest activity against E. cloacae. The MICs for all strains were equal to or lower than 0.5 microgram/ml. The MIC90S of ciprofloxacin (CPFX) and TFLX were 1 microgram/ml, the MIC90 of AMK was 2 micrograms/ml, the MIC90S of CZOP, GM and ofloxacin (OFLX) were 4 micrograms/ml. The MIC50S of cephems except CEZ, cefmetazole (CMZ) and cefaclor (CCL) had changed into a better state in 1996, compared with those in 1995. 7. Escherichia coli All drugs except penicillins and MINO were active against E. coli. Particularly CPR, CZOP and IPM showed the highest activities against E. coli. The MIC90S of them were 0.125 microgram/ml or below. Among E. coli strains, those with low susceptibilities to cephems except CEZ, cefoperazone (CPZ), latamoxef (LMOX) and CCL have increased in 1996, compared with those in 1995. 8. Klebsiella pneumoniae K. pneumoniae was susceptible to all drugs except penicillins, with the MIC90S of 2 micrograms/ml or below. CPR had the strongest activity, the MICs for all strains were equal to or lower than 0.25 microgram/ml. Flomoxef (FMOX), cefixime (CFIX), CZOP and carumonam (CRMN) were also active with the MIC90S of 0.125 microgram/ml or below. 9. Pseudomonas aeruginosa All drugs except quinolones were not so active against P. aeruginosa with the MIC90S were 32 micrograms/ml or above. Quinolones were more active in 1996 than 1995. The MIC90S of them were between 4 micrograms/ml and 8 micrograms/ml, and the MIC50S of them were between 1 microgram/ml and 2 micrograms/ml. 10. Serratia marcescens GM showed the highest activity against S. marcescens. Its MIC90 was 1 micro     

Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1993). I. Susceptibility distribution

The frequencies of isolation and susceptibilities to antimicrobial agents were investigated on 657 bacterial strains isolated from patients with urinary tract infections in 10 hospitals during the period of June 1993 to May 1994. Of the above total bacterial isolates, Gram-positive bacteria accounted for 28.3% and a majority of them were Enterococcus faecalis. Gram-negative bacteria accounted for 71.7% and most of them were Escherichia coli. 1. Enterococcus faecalis Ampicillin (ABPC), imipenem (IPM) and vancomycin (VCM) showed the highest activities against E. faecalis isolated from patients with urinary tract infections. The MIC90s of them were 2 micrograms/ml. Piperacillin (PIPC) was also active with the MIC90 of 8 micrograms/ml. The others were not so active with the MIC90s of 32 micrograms/ml or above. 2. Staphylococcus aureus including MRSA VCM showed the highest activities against S. aureus isolated from patients with urinary tract infections. Its MIC90 was 1 microgram/ml. Arbekacin (ABK) was also active with the MIC90 of 2 micrograms/ml. The others were not so active with the MIC90s of 32 micrograms/ml or above. 3. Staphylococcus epidermidis VCM showed the strongest activity against S. epidermidis isolated from patients with urinary tract infections. Its MIC90 was 1 microgram/ml. ABK was also active with the MIC90 of 4 micrograms/ml. The others except ABPC were not so active with the MIC90s of 32 micrograms/ml or above. 4. Streptococcus agalactiae Most of the agents were active against S. agalactiae isolated from patients with urinary tract infections. Penicillins, cephems, erythromycin (EM), and clindamycin (CLDM) showed the highest activities. The MIC90s of them were 0.25 microgram/ml or below. Amikacin (AMK) and minocycline (MINO) showed somewhat low activities with the MIC90s of 16 micrograms/ml. 5. Citrobacter freundii IPM showed the highest activities against C. freundii isolated from patients with urinary tract infections. Its MIC90 was 2 micrograms/ml. Cefozopran (CZOP) and gentamicin (GM) were also active with the MIC90s of 8 micrograms/ml. Penicillins and cephems generally were not so active. 6. Enterobacter cloacae IPM and GM showed the highest activities against E. cloacae. The MIC90s of them were 1 microgram/ml. CZOP and tosufloxacin (TFLX) were also active with the MIC90s of 8 micrograms/ml. Penicillins and cephems except CZOP showed lower activities with the MIC90s of 64 micrograms/ml or above. 7. Escherichia coli Most of antimicrobial agents were active against E. coli. Flomoxef (FMOX), CZOP, IPM, CPFX and TFLX showed the highest activities against E. coli. The MIC90s of them were 0.125 microgram/ml or below. Cefmenoxime (CMX), ceftazidime (CAZ), cefuzonam (CZON), latamoxef (LMOX), carumonam (CRMN), norfloxacin (NFLX) and ofloxacin (OFLX) were also active with the MIC90s of 0.25 microgram/ml. Penicillins and MINO were not so active with the MIC90s of 32 micrograms/ml or above. 8. Klebsiella pneumoniae CZOP, IPM and CRMN showed the highest activities against K. pneumoniae. The MIC90s of them were 0.125 microgram/ml or below. CAZ, CZON, CFIX, CPFX and TFLX were also active the MIC90s of 0.25 microgram/ml. Penicillins were not so active with the MIC90s of 128 micrograms/ml or above. 9. Proteus mirabilis P. mirabilis was susceptible to a majority of drugs. CMX, CAZ, CZON, LMOX, CFIX, CRMN and CPFX showed the highest activities against P. mirabilis isolated from patients with urinary tract infections. The MIC90s of them were 0.125 microgram/ml or below. MINO was not so active with the MIC90 of 256 micrograms/ml or above. 10. Pseudomonas aeruginosa Most of the agents were not so active against P. aeruginosa. IPM showed MIC90 of 8 micrograms/ml.     

Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1995). II. Background of patients

Clinical background was investigated on patients with urinary tract infections (UTIs) from whom 785 bacterial strains were isolated in 11 hospitals during the period from June, 1995 through May, 1996. 1. Distributions of age and sex of patients and type of infections. Among the patients examined, those with ages 50 years or older were the most frequent (males: 80.5%, females: 69.7%), and, among females, those with ages in the 20's were 12.6%. With regard to types of infections, more than a half of infections among males were of complicated types, but most of infections among females were of uncomplicated types, especially among females of ages less than 60 years. 2. Ages of patients and types of pathogens. The higher the ages of patients, the lesser became the isolation frequencies of Proteus spp. and Serratia spp., but the higher were those of Klebsiella spp. and Pseudomonas spp. 3. Effect of antibiotic use on isolation frequencies of pathogens. Use of antibiotics decreased pathogens isolated from patients with uncomplicated UTIs drastically (237 isolates before antibiotics compared to 33 after). Even isolated pathogens from patients with complicated UTIs decreased drastically with the use of antibiotics when indwelling catheters were not in use (200 isolates before antibiotics compared to 83 after), but when indwelling catheters were in use, antibiotics apparently failed to decrease the isolation frequency. 4. Surgical procedures and types of causative organisms for UTIs. Escherichia coli was the most frequently isolated organism from uncomplicated cases of UTIs. From cases of complicated UTIs without indwelling catheters, Enterococcus faecalis was the most frequently isolated, followed by E. coli, P. aeruginosa and Klebsiella spp. When a surgical procedures were not done, E. coli was isolated most frequently. From cases of complicated UTIs with indwelling catheters, P. aeruginosa, E. faecalis and S. aureus were the organisms that were mainly isolated, with isolation frequencies of 23.9%, 17.3% and 12.7%, respectively. When no surgical procedures were used, isolation frequencies of P. aeruginosa, Klebsiella spp. and E. faecalis were 25.7%, 14.3% and 14.3%, respectively.     

Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1996), III. Secular changes in susceptibility]

Susceptibilities to various antimicrobial agents were examined for Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Klebsiella spp., and Pseudomonas aeruginosa that were isolated from patients with urinary tract infections (UTIs) in 10 hospitals during June 1996 to May 1997, and the results were compared with those obtained during the same period in earlier years. 1. E. faecalis Among E. faecalis strains, those with high susceptibilities to ampicillin and minocycline appeared to have decreased in the latest study period. 2. S. aureus To almost antimicrobial agents, S. aureus isolated from uncomplicated UTIs showed low susceptibilities. But the MIC50s of those agents for S. aureus from complicated UTIs have changed better state. Particularly, the MIC50s of imipenem and clindamycin were 0.125 microgram/ml or below in the latest period for the first time in our history. 3. E. coli The susceptibilities to piperacillin and quinolones of E. coli isolated from uncomplicated UTIs were better than those isolated from complicated UTIs. 4. Klebsiella spp. The susceptibilities to almost antimicrobial agents of Klebsiella spp. have been better during the latest period, compared to those during period of 1995-1996, but to ofloxacin and ciprofloxacin have appeared to have been lower. 5. P. aeruginosa The susceptibilities to quinolones of P. aeruginosa have been better during the latest period compared those during periods of 1995-1996. But, the susceptibilities to cefozopran, carbapenems and monobactams of P. aeruginosa isolated from complicated UTIs appeared to have been lower. These susceptibility changes should be utilized in determining clinical treatments.     

Comparative susceptibility of 10 antimicrobials against Pseudomonas aeruginosa isolated from complicated urinary tract infection on 1992 & 1993 vs. 1994 & 1995

OBJECTIVES: To describe operative procedures, pathophysiological events, management strategies, and clinical outcomes after acute intraoperative brain herniation during elective neurosurgery. METHODS: Review of clinical diagnoses, operative events, postoperative CT findings, intracranial pressure, and arterial blood pressure changes and outcomes in a series of patients in whom elective neurosurgery had to be abandoned because of severe brain herniation. RESULTS: Acute intraoperative brain herniation occurred in seven patients. In each patient subarachnoid or intraventricular haemorrhage preceded the brain herniation. The haemorrhage occurred after intraoperative aneurysm rupture either before arachnoidal dissection (three) or during clip placement (one); after resection of 70% of a recurrent hemispheric astroblastoma; after resection of a pineal tumour; and after a stereotactic biopsy of an AIDS lesion. In all patients the procedure was abandoned because of loss of access to the intracranial operating site, medical measures to control intracranial pressure undertaken (intravenous thiopentone), an intraventricular catheter or Camino intracranial pressure monitor inserted, and CT performed immediately after scalp closure. The patients were transferred to an intensive care unit for elective ventilation and multimodality physiological monitoring. Using this strategy all patients recovered from the acute ictus and no patient had intracranial pressure > 35 mm Hg. Although one patient with an aneurysm rebled and died three days later the other six patients did well considering the dramatic and apparently catastrophic nature of the open brain herniation. CONCLUSIONS: There are fundamental differences in the pathophysiological mechanisms, neuroradiological findings, and outcomes between open brain herniation occurring in post-traumatic and elective neurosurgical patients. The surprisingly good outcomes in this series may have occurred because the intraoperative brain herniation was secondary to extra-axial subarachnoid or intraventricular haemorrhage rather than intraparenchymal haemorrhage or acute brain oedema. Expeditious abandonment of the procedure and closure of the cranium may also have contributed to the often very satisfactory clinical outcome.     

Corynebacterium riegelii sp. nov., an unusual species isolated from female patients with urinary tract infections

Four strains of an unknown coryneform bacterium were isolated in pure culture from females with urinary tract infections. Strong urease activity and the ability to slowly ferment maltose but not glucose were the most significant phenotypic features of this catalase-positive, nonmotile, nonlipophilic, rod-shaped bacterium which served to distinguish it from all other presently defined coryneform bacteria. Chemotaxonomic investigations demonstrated that the unknown bacterium belonged to the genus Corynebacterium. Comparative 16S rRNA gene sequence analysis revealed that the isolates were genealogically identical and represented a new subline within the genus Corynebacterium, for which the designation Corynebacterium riegelii sp. nov. is proposed. The type strain of Corynebacterium riegelii is CCUG 38180 (DSM 44326, CIP 105310).     

Mucoid encapsulated Enterococcus faecalis: an emerging morphotype isolated from patients with urinary tract infections

Three strains of encapsulated Enterococcus faecalis, which produced highly mucoid coalescing colonies on routine bacteriologic media, were isolated from urine specimens of patients with urinary tract infection. Encapsulation could be demonstrated through India ink preparations. The occurrence of this unusual enterococcal colony morphotype, which resembles that of a Gram-negative bacterium, may delay true identification.     

Comparative in vitro activities of trovafloxacin (CP-99,219) against 221 aerobic and 217 anaerobic bacteria isolated from patients with intra-abdominal infections

Four hundred thirty-eight bacteria cultured from specimens of patients with serious intra-abdominal infections were tested by agar dilution against trovafloxacin and other quinolones and antimicrobial agents. Trovafloxacin inhibited 435 strains (99.3%) at < or =2 microg/ml. All the quinolones had similar activities against Enterobacteriaceae and Pseudomonas sp., but trovafloxacin showed superior activities against streptococci, enterococci, and anaerobic organisms. Because of its excellent in vitro activities against diverse bacteria, trovafloxacin has potential use as a single agent for polymicrobial infections.     

Antimicrobial activities of major oral antibacterial agents against clinically isolated microbial strains from inpatients]

Antimicrobial activities were examined for major antibacterial agents against clinically isolated microbial strains which were isolated and identified from materials collected from inpatients with various infections in 1988, 1989 and 1990, and the following conclusions were obtained. 1. Among strains isolated each year, methicillin-resistant Staphylococcus aureus (MRSA) were found frequently. 2. CEPs-resistant Escherichia coli strains were observed among strains isolated each year. 3. Increasing tendencies in resistances of Citrobacter freundii, Enterobacter spp., Serratia marcescens to cephems and new quinolones were observed. 4. Increasing tendencies in resistances of Proteus vulgaris to ceftazidime (CAZ) and new quinolones appeared to exist. 5. Among strains isolated each year, resistances of Pseudomonas aeruginosa to CAZ and quinolones were observed in high rates, but also their resistances to imipenem appeared to increase. 6. Many of recently increasing multiple resistant bacteria seem to have different sites of drug action and/or to have non-hydrolytic modes of resistance.     

In vitro comparative activity (E test) of sparfloxacin and other 8 antimicrobial agents against bacteria isolated from patients with respiratory infections acquired in the community

Sparfloxacin is a new antimicrobial that, while maintaining a good activity against gram negative bacilli, has a better in vitro activity against gram positive bacteria such as S pneumoniae, intracellular pathogens and anaerobic bacteria. The aim of this work was to study the in vitro activity of sparfloxacin against bacteria isolated from patients with community acquired respiratory infections between October 1994 and January 1995. Using the E-test technique, we studied the susceptibility to sparfloxacin, ciprofloxacin, ampicillin, amoxicillin/clavulanic acid, cefuroxime, cefotaxime, erythromycin, methicillin and nalidixic acid of 50 strains of S pneumoniae, 50 strains of H. influenzae, 50 strains of S aureus and 50 strains of S pyogenes. Sparfloxacin was active against 100% of S pneumoniae, H influenzae and S pyogenes strains. Twenty two percent of S aureus strains were resistant and the MIC 90 was 12 micrograms/ml. Sparfloxacin showed the best in vitro activity against H influenzae and S aureus, a similar activity with ampicillin and cefotaxime against S pneumoniae and a similar activity with ampicillin but superior to all other studied antimicrobial against S pyogenes. It is concluded that sparfloxacin is a good antimicrobial for bacteria isolated from patients with respiratory infections.     

In vitro activities of antimicrobial agents, alone and in combination, against Acinetobacter baumannii isolated from blood

In vitro activities of 15 antimicrobial agents against 90 strains of Acinetobacter baumannii isolated from blood cultures from hospitalized patients were determined using the agar dilution method. Imipenem, ofloxacin, and ciprofloxacin had the best antimicrobial activity with minimum inhibitory concentrations (MIC50s) of 0.25 mu g/ml and MIC90s of 0.5-1 mu g/ml. beta-lactam antibiotics other than imipenem had poor activity, with MIC50s ranging from 8 to 64 mu g/ml and MIC90s from 32 to > or = 256 mu g/ml. The checkerboard titration method was used to study the effects of combination of two antimicrobial agents. Combinations of ceftazidime, aztreonam, imipenem, or ciprofloxacin with amikacin showed either synergistic effects or partial synergistic effects for 40.9%-86.4% of 22 tested strains. The best in vitro activity was observed with the combination of imipenem and amikacin. No antagonistic effects were observed with the combination of imipenem and amikacin. Synergistic effects were confirmed by time-kill curve studies. In conclusion, imipenem, ofloxacin, and ciprofloxacin were the three most active agents against human blood isolates of A. baumannii. The combination of a beta-lactam or ciprofloxacin with amikacin was synergistic for some of the isolates.     

Minimum inhibitory concentrations for selected antimicrobial agents against organisms isolated from the mammary glands of dairy heifers in New Zealand and Denmark

Minimum inhibitory concentrations were determined for selected antimicrobial agents against 872 bacteria isolated from intramammary infections in heifers in New Zealand (n = 401) and Denmark (n = 471). These values were reported in micrograms per milliliters. Antimicrobial agents tested against isolates from New Zealand were penicillin, cloxacillin, cephapirin, ceftiofur, novobiocin, enrofloxacin, erythromycin, and pirlimycin. The minimum inhibitory concentrations that inhibit 90% of the strains tested for these antimicrobial agents with Staphylococcus aureus were 4.0, 0.5, 0.5, 2.0, 1.0, 0.25, 0.5, and 1.0, respectively. The minimum inhibitory concentration values that inhibit 90% of the strains tested against the Staphylococcus spp. ranged from 0.5 to 1.0 for all antimicrobics. The minimum inhibitory concentrations against streptococci were < or = 0.06, 0.5, 0.13, 0.13, 4.0, 1.0, 0.13, and < or = 0.06, respectively. Antimicrobial agents tested against isolates from Denmark included penicillin, ampicillin, oxacillin, cephalothin, ceftiofur, penicillin plus novobiocin, erythromycin, and pirlimycin. Against S. aureus, the minimum inhibitory concentrations were 0.13, 0.5, 0.5, 0.5, 1.0, 0.25, 0.5, and 0.5, respectively. The minimum inhibitory concentrations against Staphylococcus spp. were 0.25, 0.25, 0.5, 0.5, 1.0, < or = 0.06, 0.13, 1.0, and 0.5, respectively. The minimum inhibitory concentrations against the streptococci were < or = 0.06, 0.13, 0.5, 0.5, 1.0, < or = 0.06, 0.13, 0.5, and 0.5, respectively. Minimum inhibitory concentration values for staphylococci from New Zealand and Denmark were similar to values reported for US isolates. Streptococci from New Zealand and Denmark had lower minimum inhibitory concentration values than did US isolates. Only ceftiofur and enrofloxacin were active against the Gram-negative bacilli.     

Prevention of subsequent urinary tract infections in women by the use of anti-adherence antimicrobial agents: a double-blind comparison of enoxacin with co-trimoxazole

A prospective, double-blinded crossover study was carried out to test whether a brief course of antibiotic therapy could eliminate bacteria adherent to uroepithelial cells and thus prolong the interval between urinary tract infections (UTIs). Thirty-two women with frequent Gram-negative urinary tract infections were randomized to receive either co-trimoxazole or enoxacin twice a day for 10 days to treat their UTI. Their urines were collected for 30 days after the onset of their UTI and quantitatively analyzed for bacteria, antibiotics, and bacteria adherent to uroepithelial cells (UECs). A subsequent infection caused the patient to be treated with the alternative antibiotic. A third infection terminated the study. Both regimens were indistinguishable in the rate of elimination of bacteria and in their inhibition of bacterial adherence to UECs for up to five days after stopping treatment. The interval between infections was inversely correlated with the number of adherent bacteria per UEC 30 days after the onset of the first UTI. Both regimens were equally effective in preventing subsequent UTI and the effect of 10 days therapy on the inhibition of bacterial adherence to UEC's did not extend beyond five days after stopping treatment.     

In vitro activity of fleroxacin against multiresistant gram-negative bacilli isolated from patients with nosocomial infections

In order to evaluate the in vitro activity of fleroxacin against nosocomial gram-negative organisms, 263 multiresistant gram-negative bacilli (203 Enterobacteriaceae and 60 non-fermenting gram-negative bacilli) were isolated from adult patients with nosocomial infections. The different patterns of resistance to eight different antimicrobial agents (ampicillin, carbenicillin, piperacillin, cephalothin, cefamandole, ceftazidime, gentamicin and amikacin) were determined by minimum inhibitory concentration (MIC), using the agar dilution method. The most prevalent multiresistant species isolated were Klebsiella pneumoniae (28.9%), Escherichia coli (24%) and Pseudomonas aeruginosa (12.2%). All these bacterial strains showed three to five resistance patterns to at least three different antibiotics. Resistance to ceftazidime was observed in at least one of the resistance patterns of isolated bacteria. The activity of fleroxacin against multiresistant enteric bacteria was excellent; these strains showed a susceptibility of 79-100%. The susceptibility of P. aeruginosa to antipseudomonal agents was low; however, the activity of fleroxacin against these strains was higher than 60% (MIC < or = 2 microg/ ml), broadly comparable with ciprofloxacin. The resistance to fluoroquinolones detected in this study was no cause for alarm (3%). Consequently, fleroxacin maintains a remarkable activity against Enterobacteriaceae and remains highly active against other gram-negative bacilli. Nevertheless, actions directed at preventing or limiting resistance will be crucial to maintain the viability of fluoroquinolones as important therapeutic agents.     

A nation-wide surveillance of pathogen in elderly patients with urinary tract infections. 2nd Report: Sensitivities of pathogen for oral antibacterial agents

A nation-wide surveillance of sensitivities of bacteria, which were isolated from elderly patients with UTIs aged more than 65 in 190 private clinics and 73 hospitals, for oral antibacterials, CPFX, OFLX, NFLX, CPDX and CCL, was conducted in August and September in 1993. Antibacterial activities of 5 agents against all 1,511 strains were intensified in CPFX, OFLX, NFLX, CPDX and CCL in that order. Major pathogens such as Enterobacteriaceae, E. faecalis, Staphylococcus spp. and P. aeruginosa were more susceptible to fluoroquinolones than cephems. The rate of resistant strains to antibacterials was higher in isolates from older patients, patients with complicated UTIs and with indwelling catheter. The representative of resistant strains was P. aeruginosa, and about 50% of the strains of P. aeruginosa were resistant to even CPFX which had the most superior antibacterial activity among the 5 agents. About 40% of the S. aureus were MRSA, which were almost resistant to the 5 agents. From the above findings, it was confirmed that a high recovery rate of strains which is less susceptible to various antibacterials is one of the refractory factors in elderly patients with UTIs, particularly in complicated UTIs and with indwelling catheter. Regardless of the size of the clinic or hospital, Fluoroquinolones are more suitable for the treatment of elderly patients with UTIs than cephems.     

Development of a rapid assay for detecting gyrA mutations in Escherichia coli and determination of incidence of gyrA mutations in clinical strains isolated from patients with complicated urinary tract infections

The MICs of ofloxacin for 743 strains of Escherichia coli isolated from 1988 to 1994 were determined by testing. The strains were from patients with urinary tract infections complicated by functional or anatomical disorders of the urinary tract. Those determined to be ofloxacin resistant (MIC, > or =12.5 microg/ml) comprised 3 of 395 strains (1.3%) from the 1988 to 1990 group, 2 of 166 strains (1.2%) from the 1991 to 1992 group, and 7 of 182 strains (3.8%) from the 1993 to 1994 group. The incidence of resistant strains increased significantly during this period. The percentage of isolates with moderately decreased susceptibilities to ofloxacin (MIC, 0.39 to 3.13 microg/ml) also rose during the same period. To determine the incidence of gyrA mutations in urinary-tract-derived strains of E. coli, we developed a simple and rapid assay based on PCR amplification of the region of the gyrA gene containing the mutation sites followed by digestion of the PCR product with a restriction enzyme. Using this assay, we examined all 182 strains isolated in 1993 and 1994 for the presence of mutations at Ser-83 and Asp-87 in the gyrA gene. Of these strains, 33 (18.1%) had mutations in the gyrA gene. The incidences of mutations at Ser-83, at Asp-87, and at both codons were 10.4 (19 strains), 4.4 (8 strains), and 3.3% (6 strains), respectively. To determine the correlation of the mutations in the gyrA gene with susceptibilities to quinolones (nalidixic acid, ofloxacin, norfloxacin, and ciprofloxacin), we further examined 116 strains for which the MICs of ofloxacin were > or =0.2 microg/ml that were chosen from the isolates in the 1988 to 1992 group. The MICs of nalidixic acid for the strains without mutations at either Ser-83 or Asp-87 were < or =25 microg/ml, whereas those for the strains with single mutations or double mutations were from 50 to >800 microg/ml. For the fluoroquinolones, significant differences in the distributions of the MICs were observed among the strains without mutations, with single mutations, and with double mutations. The accumulation of mutations in the gyrA gene was associated with an increase in fluoroquinolone resistance. Ofloxacin MICs for the majority of the strains with single and double mutations were 0.39 to 3.13 and 6.25 to 100 microg/ml, respectively. This study demonstrates a chronological increase in the percentage of not only highly fluoroquinolone-resistant strains, corresponding to those with double mutations in the gyrA gene, but also strains with moderately decreased susceptibilities to fluoroquinolones, corresponding to those with single mutations. This increase in the incidence of strains with a single mutation in the gyrA gene portends a further increase in the incidence of strains with clinically significant resistance to fluoroquinolones.     

In vitro activity of Bay 12-8039, a new 8-methoxyquinolone, compared to the activities of 11 other oral antimicrobial agents against 390 aerobic and anaerobic bacteria isolated from human and animal bite wound skin and soft tissue infections in humans

The in vitro activity of Bay 12-8039, a new oral 8-methoxyquinolone, was compared to the activities of 11 other oral antimicrobial agents (ciprofloxacin, levofloxacin, ofloxacin, sparfloxacin, azithromycin, clarithromycin, amoxicillin clavulanate, penicillin, cefuroxime, cefpodoxime, and doxycycline) against 250 aerobic and 140 anaerobic bacteria recently isolated from animal and human bite wound infections. Bay 12-8039 was active against all aerobic isolates, both gram-positive and gram-negative isolates, at < or = 1.0 microg/ml (MICs at which 90% of isolates are inhibited [MIC90s < or = 0.25 microg/ml) and was active against most anaerobes at < or = 0.5 microg/ml; the exceptions were Fusobacterium nucleatum and other Fusobacterium species (MIC90s, > or = 4.0 microg/ml) and one strain of Prevotella loeschii (MICs, 2.0 microg/ml). In comparison, the other quinolones tested had similar in vitro activities against the aerobic strains but were less active against the anaerobes, including peptostreptococci, Porphyromonas species, and Prevotella species. The fusobacteria were relatively resistant to all the antimicrobial agents tested except penicillin G (one penicillinase-producing strain of F. nucleatum was found) and amoxicillin clavulanate.