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Survey of antibiotic resistance in Pseudomonas aeruginosa by The Tokyo Johoku Association of Pseudomonas Studies.

Pseudomonas aeruginosa resistance (minimum inhibitory concentration [MIC], > or =16 microg/ml defined as resistant) to meropenem, imipenem, panipenem, piperacillin, ceftazidime, cefozopran, cefoperazone, sulbactam/cefoperazone, amikacin, and tobramycin, as well as cross-resistance profiles, were investigated in P. aeruginosa strains isolated at eight hospitals in the Johoku area, Tokyo, during November 1998. Overall, 8.3% of isolates were imipenem-resistant and 4.6% were ceftazidime-resistant. However, the incidence of antibiotic-resistant P. aeruginosa was distinctly different at each hospital. P. aeruginosa resistance to imipenem ranged from (MIC) 1 to 64 microg/ml (MIC90 32 microg/ml), and its resistance to ceftazidime ranged from 2 to more than 128 microg/ml (MIC90, 64 microg/ml). Meropenem (MIC range, < or =0.25 to 16 microg/ml) was more active than panipenem (MIC range, 2 to 64 microg/ml). Cefozopran was more active than piperacillin, cefoperazone, or sulbactam/cefoperazone, but many strains were resistant to cefoperazone (17/57). Our analysis found cross-resistance to many beta-lactams, but the degree of cross-resistance was very variable.

Anti-Bacterial Agents↗

Outer membrane proteins responsible for multiple drug resistance in Pseudomonas aeruginosa.

Three types of multiple-drug-resistant mutants which were phenotypically similar to previously described nalB, nfxB, and nfxC mutants were isolated from Pseudomonas aeruginosa PAO1 and two clinical isolates. Type 1 (nalB-type) mutants showed cross-resistance to meropenem, cephems, and quinolones. They overproduced an outer membrane protein with an apparent molecular mass of 50 kDa (OprM). Type 2 (nfxB-type) mutants showed cross-resistance to quinolones and new cephems, i.e., cefpirome and cefozopran, concomitant with overproduction of an outer membrane protein with an apparent molecular mass of 54 kDa (OprJ). Type 3 (nfxC-type) mutants showed cross-resistance to carbapenems and quinolones. They produced decreased amounts of OprD and increased amounts of a 50-kDa protein (OprN), which was almost the same molecular weight as that of OprM, but it was distinguishable from OprM by its heat modifiability on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In the presence of salicylate, the parent strains showed an increased level of resistance to carbapenems and quinolones and produced decreased amounts of OprD and increased amounts of OprN. Salicylate caused the repression of OprJ production and the loss of resistance to cefpirome and cefozopran in two of the three OprJ-overproducing mutants, although salicylate slightly increased the level of resistance in the parent strains. The changes in susceptibilities were transient in the presence of salicylate. These data suggest that at least three different outer membrane proteins, OprM, OprJ, and OprN, are associated with multiple drug resistance in P. aeruginosa.

Anti-Bacterial Agents↗

[In vitro activity of antimicrobial agents against clinical isolates of Pseudomonas aeruginosa].

Two hundred and seven clinical isolates of Pseudomonas aeruginosa were collected at Tenri Hospital between April 2003 and March 2004. We determined the minimum inhibitory concentration (MIC) of 16 antimicrobial agents, including prulifloxacin, pazufloxacin and biapenem which were recently published in Japan, against these isolates according to the guidelines of the Clinical and Laboratory Standards Institute. For the fluoroquinolones, the rank order of activity was prulifloxacin (MIC50, 0.5 microg/ml)>ciprofloxacin (1 microg/ml)> pazufloxacin (2 microg/ml)=levofloxacin (2 microg/ml)>gatifloxacin (4 microg/ml). For the carbapenems, the rank order of activity was meropenem (MIC50, 1 microg/ml)=biapenem (1 microg/ml)>imipenem (2 microg/m)>panipenem (8 microg/ml). For the cephalosporins and monobactam, the overall rank order of activity was cefozopran (MIC50, 4 microg/ml)= ceftazidime (4 microg/ml)>cefepime (8 microg/ml)=piperacillin/tazobactam (8 microg/ml)>aztreonam (16 microg/ml)= cefoperazone/sulbactam (16 microg/ml)=cefpirome (16 microg/ml). The rates of susceptibility to antimicrobial agents as per the criteria of the Japanese Society of Antimicrobial Chemotherapy were especially high for cefozopran (63%), biapenem and meropenem (61%), and pazufloxacin (53%) and ciprofloxacin (53%). These findings suggest that prulifloxacin, pazufloxacin and biapenem, which are newly introduced, are clinically effective in the treatment of infection caused with P. aeruginosa.

Anti-Bacterial Agents↗

[Susceptibilities of bacteria isolated from patients with respiratory infectious diseases to antibiotics (1994)].

Bacteria isolated from lower respiratory tract infections were collected in cooperation with institutions located throughout Japan, since 1981. IKEMOTO et al. have been investigating susceptibilities of these isolates to various antibacterial agents and antibiotics, and characteristics of the patients and isolates from them each year. Results obtained from these investigations are discussed. In 23 institutions around the entire Japan, 492 strains of presumably etiological bacteria were isolated mainly from the sputum of 421 patients with lower respiratory tract infections from October 1994 to September 1995. MICs of various antibacterial agents and antibiotics were determined against 70 strains of Staphylococcus aureus, 101 strains of Streptococcus pneumoniae, 92 strains of Haemophilus influenzae, 61 strains of Pseudomonas aeruginosa (non-mucoid strains), 25 strains of Pseudomonas aeruginosa (mucoid strains), 48 strains of Moraxella subgenus Branhamella catarrhalis, 14 strains of Klebsiella pneumoniae etc., and the drug susceptibilities of these strains were assessed except for those strains that died during transportation. 1. S. aureus. S. aureus strains for which MICs of oxacillin were higher than 4 micrograms/ml (methicillin-resistant S. aureus) accounted for 51.4%, but the frequency of the drug resistant bacteria decreased comparing to the previous year's 56.0%. Vancomycin showed the highest activity against S. aureus with MIC80 of 0.5 microgram/ml. 2. S. pneumoniae. Most of the drugs tested showed potent activities against S. pneumoniae. Imipenem of carbapenems showed the most potent activity with MIC80 was 0.063 microgram/ml. Erythromycin and clindamycin showed low activities with MIC80s > or = 256 micrograms/ml. Among these strains, however, 46.5% and 68.3% of strains, were quite sensitive toward these agents, respectively, with MICs of 0.063 microgram/ml. 3. H. influenzae. The activities of all drugs were potent against H. influenzae tested. Cefmenoxime a cephem, showed the most potent activity, the MICs of this drug against all of the 92 strains were 0.063 microgram/ml. Ofloxacin also showed a potent activity, and inhibited about 96% of strains with MIC of 0.063 microgram/ml. 4. P. aeruginosa (mucoid strains). Tobramycin showed the most potent activity against P. aeruginosa (mucoid strains) with MIC80 of 0.5 microgram/ml. Gentamicin, arbekacin and ciprofloxacin showed next potent activities, and their MIC80s were 2 micrograms/ml. 5. P. aeruginosa (non-mucoid strains). Tobramycin showed the most potent activity against P. aeruginosa (non-mucoid strains) with MIC80 of 2 micrograms/ml. Comparing to the activities against P. aeruginosa (mucoid strains), the activities of all the drugs tested were lower against P. aeruginosa (non-mucoid strains). 6. K. pneumoniae. Carumonam showed the most potent activity against K. pneumoniae with MIC80 of 0.063 microgram/ml. Cefozopran showed the next most potent activity with MIC80 of 0.125 microgram/ml. Ampicillin and cephems except cefpodoxime, cefozopran and cefditoren showed low activities and their MIC80s were > or = 16 micrograms/ml, and their MICs were all higher than > or = 4 micrograms/ml. 7. M. (B.) catarrhalis. Imipenem and ofloxacin showed the most potent activities against M. (B.) catarrhalis, their MIC80s were 0.063 microgram/ml. Erythromycin and minocycline showed the next highest activities with their MIC80s at 0.25 microgram/ml. Also, we investigated year to year changes in the background of patients, the respiratory infectious diseases, and the etiology of bacteria. Patients characteristics, in this period of investigation showed varieties of infectious diseases found in patients in a high age bracket, and the patients over age 60 accounted for 62.0% of all the cases. Different lower respiratory tract infectious were distributed as follows: chronic bronchitis and bacterial pneumonia accounted for the greatest number of cases with 35.6%, 27.1%, respectively, followed by

Adult↗

Changes in the intestinal flora after the administration of prophylactic antibiotics to patients undergoing a gastrectomy.

PURPOSE: Changes in the intestinal flora were investigated in patients administered antibiotics for 4 days after a gastrectomy. METHODS: Twenty-four patients were divided into each of the following groups: cefazolin, 1 g every 8 h; cefozopran, 0.5 g every 8 h; flomoxef, 1 g every 8 h. All drugs were administered intravenously for a 4-day period. RESULTS: Antibiotic prophylaxis caused no major change in the total number of anaerobes because of the preservation of the Bacteroides fragilis group. However, the number of Bifidobacterium, Lactobacillus, Eubacterium, and Veillonella spp. decreased by an average of 100-fold. These changes were accompanied by an overgrowth of Enterococcus spp. and Pseudomonas aeruginosa. CONCLUSIONS: Four days of antibiotic prophylaxis after surgery caused a suppression of colonization resistance in the intestinal flora. Certain genera of anaerobes may thus play an important role in preventing overgrowth of antibiotic-resistant organisms after surgery. Surgeons should decide the duration of antibiotic use after carefully considering its influence on the intestinal flora.

Adult↗

The excretion of cephem antibiotics into saliva is inversely associated with their plasma protein-binding activities.

BACKGROUND: The excretion of medicated drugs into saliva may disturb the oral environment and antibiotic excretion into saliva appears to be regulated by many factors that have not been fully explored. METHODS: Excretion of four cephem antibiotics into saliva was examined in healthy volunteers and rats, using high-performance liquid chromatography, and the relationship between excretion levels and plasma protein-binding activities of the antibiotics was investigated. RESULTS: Following addition of 50 microgram/ml of each antibiotic to human plasma, protein binding rates (PBRs) of cefuzonam (CZON, molecular weight (MW): 535.58), cefotaxime (CTX, MW: 477.45), flomoxef (FMOX, MW: 518.45) and cefozopran (CZOP, MW: 551.99) were 87.8 +/- 1.2, 70.8 +/- 0.8, 36.2 +/- 0.5 and 8.3 +/- 0.3%, respectively. In rat plasma, PBRs of the four antibiotics were 94.0 +/- 0.5, 62.1 +/- 1.4, 54.0 +/- 0.8 and 6.0 +/- 0.8%, respectively. Similar PBRs were observed when the antibiotic concentration was increased to 100 and 200 microgram/ml. CZOP was most rapidly excreted into saliva and had the highest concentration in saliva among the tested antibiotics, while the plateau level of CZON was the lowest. The excreted levels of each antibiotic in saliva, when locally perfused through the rat facial artery, were inversely associated with each PBR. Similarly, the ratios of antibiotic concentration in saliva to rat plasma were almost constant for each antibiotic, revealing an inverse relationship with PBRs. CONCLUSION: These results appear to indicate that low molecular weight antibiotics are excreted into saliva through passive diffusion, inversely relating to their PBRs, and that high concentrations of antibiotics in the saliva have the potential to change the oral ecological environment.

Adult↗

Characteristics of Pseudomonas corneal infection related to orthokeratology.

PURPOSE: To describe a Pseudomonas aeruginosa corneal infection resulting from orthokeratology. METHODS: Case report. RESULTS: A 17-year-old boy wearing orthokeratology (OK) lenses was referred to our clinic because of redness in his right eye in spite of his usage of ofloxacin (OFLX) eye drops. An excavated paracentral corneal ulcer with an immune ring and hypopyon was observed. It was positioned under the paracentral steeper portion of the optic of the OK lens. Culture of the lens solution revealed P. aeruginosa. The patient was treated with topical OFLX and cefmenoxime (CMX) plus intravenous and subconjunctival injections of cefozopran (CZOP), successfully. The antibiotic susceptibility of P. aeruginosa by the disk diffusion susceptibility test was reduced under moderately hypoxic conditions. Glycocalyx slime was formed on the OK lens in vitro by P. aeruginosa isolated from the case. CONCLUSIONS: Changes in P. aeruginosa susceptibility to antibiotics under moderately hypoxic conditions and glycocalyx slime formation might affect the features of OK lens-associated infections.

Administration, Topical↗

Effects of parenterally administered ciprofloxacin in a murine model of pulmonary Pseudomonas aeruginosa infection mimicking ventilator-associated pneumonia.

BACKGROUND AND METHODS: We compared the bacteriological, pharmacological and histopathological effects of parenterally administered ciprofloxacin (CPFX) to those of imipenem/cilastatin (IMP/CS) and cefozopran (CZOP) in a murine model of mucoid Pseudomonas aeruginosa pneumonia mimicking ventilator-associated pneumonia. RESULTS: The minimum inhibitory concentrations (MICs) of CPFX, IMP and CZOP were 1.0, 1.0 and 4.0 mg/l, respectively. Treatment with CPFX resulted in a significant decrease in the number of viable bacteria [control, IMP/CS, CZOP and CPFX (mean +/- SEM): 5.02 +/- 0.20, 4.96 +/- 0.38, 5.44 +/- 0.13 and 3.27 +/- 0.02 log(10) colony-forming units lung, respectively]. Histopathological examination revealed that inflammatory changes in the CPFX-treated group were less marked than in other groups. Of the drugs analyzed, the pharmacokinetic parameters of area under the time-concentration curve (AUC)/MIC, AUC exceeding MIC and the time that lung concentrations of drug remained above the MIC were highest for CPFX. CONCLUSION: Our results suggest that parenterally administered ciprofloxacin is effective in ventilator-associated P. aeruginosa pneumonia.

Animals↗

In vitro combined effects of cefozopran/teicoplanin and cefozopran/vancomycin on methicillin-resistant Staphylococcus aureus.

We determined the in vitro effects of teicoplanin (TEIC) or vancomycin (VCM) added to cefozopran (CZOP) on 50 methicillin-resistant Staphylococcus aureus (MRSA) strains, using a modified checkerboard method with serial 1.25-fold dilutions, and assessed the time-kill curve. CZOP + TEIC was synergistic (fractional inhibitory concentration index < or = 0.5) against 98% and CZOP + VCM against 20% of strains. Both drug combinations were additive against the remaining strains. A comparison of the fractional bactericidal concentration indices for 32 strains showed synergistic bactericidal effects for CZOP + TEIC in 88%, and in 48% for CZOP +VCM, confirming that CZOP + TEIC is superior to CZOP + VCM. The time-kill curve confirms that the bactericidal potency of these drugs is increased through combined use with CZOP. These results suggest that treatment using TEIC or VCM with CZOP may be useful in treating MRSA infections, including polymicrobial infections and those involving Gram-negative rods.

Anti-Bacterial Agents↗

[The trend and susceptibility to antibacterial agents of enterococcus species from urinary tract infections].

OBJECTIVE: To determine the extent of drug-resistance among Enterococcus species we investigated in vitro experiments. METHODS: Studies were carried out on pure cultured of enterococci isolated from 8,575 urine specimens between 1990 and 2002. We had determined test strains to three kinds of species, which posses the urinary pathogenesis. Both an EF-agars and an ADH decarboxylase test performed the identification and speciation of the strains of enterococci. In vitro drug-susceptibility tests of enterococci were performed against the following antibiotics: ampicillin (ABPC), cefpirome (CPR), cefozopran (CZOP), imipenem/cilastatin (IPM/CS), minocycline (MINO), levofloxacin (LVFX), vancomycin (VCM), sulfamethoxazone/trimethoprim (ST), by employing the method for dilution antimicrobial susceptibility tests for bacteria that grow aerobically recommended by Japan Society of Chemotherapy. These drug-susceptibilities were shown susceptible, intermittent and resistant in according to National Committee for Clinical Laboratory Standards (M100-S12). RESULTS: The most common species isolated was E. faecalis (84.4%), followed by E. faecium (9.9%) and E. avium (5.6%). In E. faecium and E. avium, the sensitivity to ABPC has tended to improve from 1999. This tendency inverse correlated to decreasing dosage of PCs. There was much difference of resistant rate to IPM/CS between each species, and no correlation to used dosage of CBPs. The rate of resistance to MINO did not change during this period. 60% of E. faecalis had sensitivity to LVFX and the rate did not change during this period. In E. faecium, whose resistant rate to LVFX was 90%, the sensitivity has been improved to over 25% from 2001. The improved tendency of E. faecium to LVFX has inverse proportion to decreasing dosage of NQs. With the exception of a little bit VRE (VCM resistant Enterococci), almost of them had sensitivity to VCM. CONCLUSION: The emergence of enterococci with alarming rates of resistance concomitantly to multi-drugs highlights the need for a more rational and restricted use of antimicrobials, in order to minimize the selection and spread of such strains. An early detection of these problem pathogens is also important for preventing any treatment failures.

Ampicillin Resistance↗

Studies on anti-MRSA parenteral cephalosporins. I. Synthesis and antibacterial activity of 7beta-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)- hydroxyiminoacetamido]-3-(substituted imidaz.

In order to improve the antibacterial activity of cefozopran (CZOP) against methicillin-resistant Staphylococcus aureus (MRSA), we initiated chemical modification to introduce a 2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)-hydroxyimino acetyl group at the C-7 position and a 3- or 6-substituted imidazo[1,2-b]pyridazinium or 5-substituted imidazo[1,2-a]pyridinium group at the C-3' position. Although this approach successfully enhanced the anti-MRSA activity of CZOP two to eight times, a slight decrease in the activity against Gram-negative bacteria including Pseudomonas aeruginosa was involved. Among the novel derivatives, 3-(6-aminoimidazo[1,2-b]pyridazinium-1-yl)methyl-7beta-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)hydroxyiminoacetamido]-3-cephem-4-carboxylate (44a) showed an excellent balance of activity against MRSA and Gram-negative bacteria.

Animals↗

Studies on anti-MRSA parenteral cephalosporins. II. Synthesis and antibacterial activity of 7beta-[2-(5-amino-1,2,4- thiadiazol-3-yl)-2(Z)-alkoxyiminoacetamido]-3-(substituted imidaz.

In an effort to discover a novel cefozopran (CZOP) derivative having excellent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), we performed chemical modification of the alkoxyimino moiety and imidazo[1,2-b]pyridazinium group of CZOP. Among the prepared compounds, the cyclopentyloxyimino derivative 7beta-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)-cyclopentyloxyiminoacetamido]-3-(3,6-diaminoimidazo[1,2-b]pyridazinium-1-yl)methyl-3-cephem-4-carboxylate (20 g) showed the most potent anti-MRSA activity, reflecting its high affinity (IC50 = 1.6 microg/ml) for penicillin binding protein 2' (PBP2'), although its anti-MRSA activity was slightly inferior to that of vancomycin (VCM). In experimental systemic infection in mice, however, 20 g showed activity comparable to that of VCM against MRSA. In addition, 20 g showed activity similar or slightly inferior to that of CZOP against Pseudomonas aeruginosa both in vitro and in vivo. Considering its favorable antibacterial activity profile, 20 g was considered to be the most promising CZOP derivative for further studies.

Animals↗

[In vitro and in vivo activities of panipenem against penicillin-resistant Streptococcus pneumoniae].

Efficacy of panipenem/betamipron (PAPM/BP) against experimental pneumonia caused by penicillin-resistant Streptococcus pneumoniae (PRSP: MIC of benzylpenicillin, > or = 1.56 micrograms/ml) in mice was compared with those of imipenem/cilastatin (IPM/CS), meropenem (MEPM), cefozopran (CZOP), ceftriaxone (CTRX), ampicillin (ABPC), and vancomycin (VCM). The infection was induced by inoculating a PRSP clinical isolate, 9601 (serotype 6) or 10,693 (serotype 19), into ddY male mice intranasally. Drugs were administered subcutaneously at doses of 0.4, 2, and 10 mg/kg, 18, 26, 42, and 50 hours post-infection. Viable cell counts in the lungs were determined 66 hours post-infection. PAPM/BP showed the greatest efficacy against the infections among tested drugs. MICs of PAPM against PRSP 9601 and 10,693 were both 0.125 microgram/ml, which were superior to those of IPM (0.25 and 0.5 microgram/ml, respectively), MEPM (0.5 and 1 microgram/ml, respectively), CZOP (2 and 1 microgram/ml, respectively), CTRX (both 1 microgram/ml), ABPC (both 4 micrograms/ml), and VCM (0.5 and 0.25 microgram/ml, respectively). These results suggest that the potent in vivo activity of PAPM/BP reflects the potent in vitro activity of PAPM. MICs of PAPM, IPM, MEPM, and CZOP against clinical isolates, penicillin-susceptible S. pneumoniae (PSSP: MIC of benzylpenicillin, < or = 0.05 microgram/ml), penicillin-intermediate S. pneumoniae (PISP: MIC of benzylpenicillin, 0.1-0.78 microgram/ml), and PRSP, were tested by an agar dilution method. MIC90s of the drugs against the PSSP, PISP, and PRSP were as follows: PAPM, 0.012, 0.05, and 0.39 microgram/ml; IPM, < or = 0.006, 0.1, and 0.78 microgram/ml; MEPM, 0.05, 0.39, and 1.56 micrograms/ml; and CZOP, 0.2, 0.78, and 6.25 micrograms/ml, respectively. Thus, PAPM showed the most potent activity among tested drugs against clinical isolates of PISP and PRSP.

Ampicillin↗

[Antimicrobial activities of carbapenems and fourth generation cephems against clinically isolated strains].

We determined the antibacterial activities of 4 carbapenems (imipenem, panipenem, meropenem and biapenem) and 2 forth generation cephems (cefozopran and cefepime) against 850 bacterial strains (18 species) isolated during the period from January 1998 through September 2000. The 4 carbapenems showed excellent antibacterial activities against methicillin-susceptible S. aureus (MSSA), S. pneumoniae, E. faecalis, P. aeruginosa, M. (B). catarrhalis, B. fragilis and Peptostreptococcus spp. as compared with the cephems except the activity of panipenem against P. aeruginosa. Meropenem showed the highest antibacterial activity against 10 species of all Gram-negative strains determined. The antibacterial activities of 2 forth generation cephems against 6 species of Enterobacteriaceae were equal to or higher than those of carbapenems except meropenem. All drugs showed low antibacterial activities against methicillin-resistant S. aureus (MRSA).

Bacteria↗

[A case of AIDS-associated Haemophilus influenzae pneumonia with diffuse reticulonodular shadows].

A 32-year-old male was admitted to our hospital complaining of fever and dyspnea on effort. Laboratory data on admission indicated leukocytosis and elevation of C-reactive protein. A chest radiograph showed diffuse reticulonodular shadows in both lower lung fields, and a chest computed tomography showed centrilobular reticulonodular opacity. Bronchoscopic findings revealed a large amount of slightly yellowish secretion in all bronchi. Cells found in the bronchoalveolar lavage fluid (BALF) included 61% neutrophils. Haemophilus influenzae was isolated from cultures of the BALF and sputum. Transtracheal lung biopsy specimens showed focal infiltration of neutrophils in the alveoli, and the pathological findings in the lung were compatible with bronchiolopneumonia. Since the CD4/CD8 ratio was 0.09 and a positive reaction was obtained for anti-human immunodeficiency virus (HIV) antibody, HIV-associated pneumonia due to H. influenzae was diagnosed. Seven days' administration of cefozopran improved the patient's condition. It is interesting that radiological findings are often unusual in HIV-infected patients with H. influenzae pneumonia.

Acquired Immunodeficiency Syndrome↗

Successful treatment of cervical spinal epidural abscess by combined hyperbaric oxygenation.

A 49-year-old man underwent hyperbaric oxygen (HBO) therapy for the treatment of primary spinal epidural abscess. Although the epidural abscess was initially treated with antibiotic (cefozopran) for 5 days, he subsequently developed motor weakness, paresthesia and urinary retention. MRI demonstrated spinal cord compression at the C1-C4 level. HBO therapy was added to the antibiotic regimen, and three days later we found clinical evidence of a response to treatment. Neurological symptoms were relieved 13 days after HBO therapy. This case suggests that HBO therapy is an effective therapeutic adjunct for the treatment of spinal epidural abscess.

Anti-Bacterial Agents↗

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2004). I. Susceptibility distribution].

The bacterial strains isolated from 490 patients diagnosed as having urinary tract infections (UTIs) in 14 institutions in Japan were collected between August 2004 and July 2005. The susceptibilities of them to many kinds of antimicrobial agents were measured. Of them, 577 strains were estimated as causative bacteria and used for the measurement. The strains consisted of 156 gram-positive bacterial strains (27.0%) and 421 gram-negative bacterial strains (73.0%). Against Staphylococcus aureus, arbekacin (ABK), vancomycin (VCM) showed the strongest activity and prevented the growth of all strains with 2 microg/mL. Against Enterococcus faecalis, ampicillin (ABPC) and VCM showed a strong antibacterial activity. The antibacterial activity of cephems to Escherichia coli was generally good, and especially cefozopran (CZOP) and cefpirome (CPR) showed the strongest activity (MIC90: < or = 125 microg/mL). Quinolone resistant E. coli [MIC of ciprofloxacin (CPFX): > or = 4 microg/mL] was detected at frequency of 18.8%, which was higher than that in the last year. Against Klebsiella pneumoniae, CZOP, meropenem (MEPM), and carumonam (CRMN) showed the strongest activity and prevented the growth of all strains with 0.125 microg/mL or less. The antibacterial activity of the other cephems was relatively good, and decrease in their activity observed in the last year study was not recognized. Against Serratia marcescens, imipenem (IPM) and gentamicin (GM) had the strongest antibacterial activity. Against Proteus mirabilis, CRMN showed the strongest activity and prevented the growth of all strains with 0.125 microg/mL or less. MEPM prevented the growth of all strains with 0.25 microg/mL. Next, cefmenoxime (CMX), ceftazidime (CAZ), CZOP, cefixime (CFIX), cefpodoxime (CPDX), and cefditoren (CDTR) showed a strong activity. The antibacterial activity of the drugs to Pseudomonas aeruginosa was generally low, and MIC90 of all the drugs was ranged from 32 to > 128 microg/mL except IPM and MEPM having 16 microg/mL. The antibacterial activities of CZOP and CAZ were considered to be relatively good on MIC50 comparison (MIC50: 2 microg/mL).

Aminoglycosides↗

[The antimicrobial susceptibilities and serotypes of Pseudomonas aeruginosa isolated from sputum].

During the period of January 1992 and August 1995, 75 strains of Pseudomonas aeruginosa were isolated from sputum at the Hiroshima Prefectural Hiroshima Hospital. The antimicrobial susceptibilities and serotypes of those strains were investigated. The results are summarized as follows: 1. The analyses of antimicrobial susceptibilities revealed that meropenem (MEPM) was the most active among the carbapenems tested against those P. aeruginosa strains with MIC of < or = 6.25 micrograms/ml. All of the strains were thus found to be susceptible to MEPM, while 9 strains out of 75 (12%) were resistant to imipenem showing cross-resistance to biapenem. 2. The activities of the beta-lactams other than carbapenems were found to be the order of cefozopran > or = ceftazidime > aztreonam > piperacillin with MIC50 and MIC90 ranging of 3.13-6.25 micrograms/ml and 25- > or = 100 micrograms/ml, respectively. 3. Among aminoglycosides tested, 3 strains (4.0%) of the strains showed resistance to amikacin, however none of them were resistant to tobramycin. 4. Distribution of serotypes among the strains was; type G 22.7%, type M 21.3%, type A 16.0%, type B 13.3% and type E 8.0%. Strains of types M and E showed multiple resistance to beta-lactams except carbapenems. As documented in this study, the frequency of isolation of beta-lactam-resistant P. aeruginosa (including carbapenem-resistant) is steadily increasing. Continuous surveillance of antimicrobial susceptibility among clinically isolated P. aeruginosa seems to be necessary.

Anti-Bacterial Agents↗