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[Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1988). III. Secular changes in susceptibility].

Sensitivities to various antibacterial and antibiotic agents of strains of Escherichia coli, Klebsiella spp., Proteus spp., Citrobacter spp., Enterobacter spp., Serratia marcescens and Pseudomonas aeruginosa isolated from patients with urinary tract infections (UTIs) in 9 hospitals during June to November 1988 were compared with those in the same period of previous year according to a classification, uncomplicated UTIs, complicated UTIs without indwelling catheter, and complicated UTIs with indwelling catheter. No remarkable changes were found in sensitivities of E. coli, Proteus spp., Citrobacter spp. and S. marcescens. The sensitivity of Klebsiella spp. to cephems decreased in complicated UTI without indwelling catheter and increased in complicated UTI with indwelling catheter. The sensitivity of Enterobacter spp. to third generation cephems decreased in complicated UTI with indwelling catheter. Sensitivities of P. aeruginosa to aspoxicillin and cefsulodin increased. The number of resistant strains to new quinolones increased slightly.

Anti-Bacterial Agents↗

[Yearly changes in antibacterial activities of cefozopran against various clinical isolates between 1996 and 2001--II. Gram-negative bacteria].

The in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems, against various clinical isolates obtained between 1996 and 2001 were yearly evaluated and compared with those of other cephems, oxacephems and carbapenems. A total of 3,245 strains in 32 species of Gram-negative bacteria were isolated from the clinical materials annually collected from January to December, and consisted of Moraxella subgenus Branhamella catarrhalis, Escherichia coli, Citrobacter freundii, Citrobacter koseri, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter cloacae, Serratia marcescens, Proteus mirabillis, Proteus vulgaris, Morganella morganii, Providencia spp. (P. alcalifaciens, P. rettgeri, P. stuartii), Pseudomonas aeruginosa, Pseudomonas putida, Burkholderia cepacia, Stenotrophomonas maltophilia, Haemophilus influenzae, Acinetobactor baumannii, Acinetobactor lwoffii, Bacteroides fragilis group (B. fragilis, B. vulgatus, B. distasonis, B. ovatus, B. thetaiotaomicron), and Prevotella spp. (P. melaninogenica, P. intermedia, P. bivia, P. oralis, P. denticola). CZOP possessed stable antibacterial activities against M. (B.) catarrhalis, E. coli, C. freundii, C. koseri, K. pneumoniae, K. oxytoca, E. aerogenes, E. cloacae, S. marcescens, P. mirabilis, P. vulgaris, M. morganii, Providencia spp., P. aeruginosa, and A. lwoffii throughout 6 years. The MIC90 of CZOP against those strains were consistent with those obtained from the studies performed until the new drug application approval. On the other hand, the MIC90 of CZOP against H. influenzae yearly obviously increased with approximately 64-time difference during the study period. The MIC90 of cefpirome, cefepime, and flomoxef against H. influenzae also yearly tended to rise. The present results demonstrated that CZOP had maintained the antibacterial activity against almost Gram-negative strains tested. However, the decrease in antibacterial activities of CZOP against B. cepacia, and H. influenzae was suggested.

Cefepime↗

[Post-marketing surveillance of antibacterial activities of cefozopran against various clinical isolates--II. Gram-negative bacteria].

As a post-marketing surveillance, the in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems, against various clinical isolates were yearly evaluated and compared with those of other cephems, oxacephems, carbapenems, monobactams, and penicillins. Changes in CZOP susceptibility among bacteria were also evaluated with the bacterial resistance ratio calculated from the breakpoint MIC. Twenty-five species (4,154 strains) of Gram-negative bacteria were isolated from the clinical materials annually collected from 1996 to 2001, and consisted of Moraxella (Branhamella) catarrhalis, Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, Enterobacter aerogenes, Serratia marcescens, Serratia liquefaciens, Citrobacter freundii, Citrobacter koseri, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia spp., Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas putida, Acinetobacter baumannii, Acinetobacter Iwoffii, Burkholderia cepacia, Stenotrophomonas maltophilia, Bacteroides fragilis group, and Prevotella/Porphyromonas. CZOP preserved its antibacterial activity against M. (B.) catarrhalis (MIC90: 4 micrograms/mL) and showed comparable activity to carbapenems against H. influenzae (MIC90: 1 microgram/mL). The antibacterial activity of CZOP against E. coli was preferable (MIC90: 0.125 microgram/mL) and comparable to those of cefpirome (CPR), cefepime (CFPM), and imipenem (IPM). The MIC90 of CZOP against K. pneumoniae and K. oxytoca was 1 and 0.25 microgram/mL, respectively. The MIC90 of CZOP against E. cloacae increased during 6 years (32 to 128 micrograms/mL). The antibacterial activity of CZOP against E. aerogenes was preferable (MIC90: 1 microgram/mL). The antibacterial activities of CZOP against S. marcescens and S. liquefaciens were relatively potent (MIC90: 0.5 and 0.25 microgram/mL) and comparable to those of CPR, CFPM, and carumonam. CZOP preserved comparable antibacterial activity to CPR against C. freundii and C. koseri (MIC90: 8 and 0.125 micrograms/mL). The MIC90 of CZOP against P. mirabilis, P. vulgaris, and M. morganii was 0.25, 16, and 2 micrograms/mL, respectively. The antibacterial activity of CZOP against Providencia spp. was moderate (MIC90: 64 micrograms/mL). The antibacterial activity of CZOP against P. aeruginosa was the most potent (MIC90: 16 micrograms/mL) among the test agents and comparable to those CFPM, IPM, and MEPM. CZOP had low activity against P. fluorescens and P. putida (MIC90: 128 micrograms/mL). The antibacterial activity of CZOP against A. baumannii was comparable to those of ceftazidime (CAZ), CPR and CFPM (MIC90: 32 micrograms/mL) and against A. lwoffii was moderate (MIC90: 64 micrograms/mL). Most of the test agents including CZOP had low antibacterial activity against B. cepacia, S. maltophilia, and B. fragilis group. The MIC90 of CZOP against Prevotella/Porphyromonas was 64 micrograms/mL. Bacterial cross-resistance ratio between CZOP and other agents was low in most of the species, ranging from 0.0 to 15.1%. In non-glucose fermentative bacteria, however, the bacterial cross-resistance ratio between CZOP and CFPM, CAZ, CPR, or IPM was high, being 36.8%, 28.0%, 38.7%, or 31.1%, respectively. In conclusion, the 6-year duration study suggested that the antibacterial activity of CZOP against E. cloacae possible decreased, but against other Gram-negative bacteria was consistent with the study results obtained until the new drug application approval.

Carbapenems↗

Correlation of extended spectrum beta lactamases production with cephalosporin resistance in gram negative bacilli.

Beta lactamase production is an important mechanism of developing resistance to beta lactam group of antibiotics. Cephlosporins with extended spectrum of activity and stability were introduced to overcome this resistance, but soon production of extended spectrum beta lactamases (ESBLs), which are inducible in nature was reported. In this study Klebsiella aerogenes--166, Escherichia coli--120, Citrobacter spps--116, Pseudomonas spps--50, Proteus spps--32 and S. typhi--16, strains were subjected to sensitivity testing against various generations of cephalosporins by disc diffusion method and for the production of ESBLs using disc approximation method. Klebsiella aerogenes, Escherichia coli, Citrobacter spps and Pseudomonas spps showed statistically significant difference in the resistance pattern to all three generations of cephalosporins and ESBLs production.

Cephalosporin Resistance↗

[Bacterial causes of meningitis in newborns].

INTRODUCTION: Bacterial meningitis jeopardizes the life of affected newborns and in survived children often leaves permanent sequels. The sooner the diagnosis is established and the therapy is started, the more a prosperous outcome can be expected. When the indication is established, lumbar punction should be performed. On the basis of the results of cytological and biochemical analyses of the cerebrospinal fluid (CSF) that point to bacterial meningitis, the initial therapy should begin even before the results of bacteriological analyses. It is important to know which causes are to be expected in order to make an adequate choice of antibiotics for initial therapy. The AIM of this study is to identify the causes of meningitis, frequency of their occurrings and mortality-rate in the affected newborns. PATIENTS AND METHODS: A prospective study was carried out in the Paediatric Department of the Institute from January 1, 1978 to December 31, 2000. Patients originated from all parts of Yugoslavia. After the establishing of indication, lumbar punction was performed. CSF was sent to cytological, biochemical and bacteriological analyses. Diagnosis of meningitis was established when at least two criteria of four were fulfilled: 1. isolation of the cause by CSF culture; 2. elevation of CSF leukocyte count more than 20 with predominance of polymorphonuclear leukocytes; 3. hypoglucorrhachia (glycaemia less than 40 mg percent or less than 50 percent of glycaemia); 4. identification of bacteria by the Gram stain of CSF sediment. In 173 newborns the cause of bacterial meningitis was confirmed. RESULTS AND DISCUSSION: Causes of meningitis were as follows: E. coli in 46 newborns (N) (26.5%), Streptococcus B haemolyticus group B in 35 N (20.2%), K. pneumoniae in 27 N (15.6%), K. oxytoca in 3 N (1.7%), Proteus spp in 14 N (8%), Salmonella spp in 12 N, Pseudomonas spp in 9 N, Streptococcus pneumoniae in 9 N, Acinetobacter calcoaceticus in 4 N, Enterobacter spp in 3 N, L. monocytogenes and Serratia marcescens and Staphylococcus aureus in 2 N each, and in one N. meningitidis, Streptococcus group D, Citrobacter, Morganella morganii and Alkaligenes xilosoxidans. Over the period 1978-1987, the most frequent causes were: E. coli (28.2%), SBHB (26.8%) and Klebsiella spp (11.3%). Over the period 1991-2000, order and frequency of causes had been changed: Klebsiella spp (26.8%), E. coli (19.2%), SBHB (14.1%), etc. In addition, new causes appeared, namely: Morganella morganii, Citrobacter, K. oxitoca and Alkaligenes xylosoxidans (Table 2). Of a total of 173 patients, 52 (30.1%) died: of 124 children with meningitis caused by gram-negative bacteria, 39 (31.4%) died, and of 49 children with gram-positive bacteria, 13 (26.5%) died (Table 1). Comparing the first and the last decade, mortality decreased by only 0.2% (Table 2). The explanation might be that the patients came to the Institute too late, and after manifestation of resistant and multiresistant causes that obscured the appropriate selection of antibiotics for initial therapy. The precious time between the onset of the disease and start of the therapy was lost in this way. Newborns with bacterial meningitis should be treated only in health institutions where the intensive care units for newborns exist. CONCLUSION: The most frequent causes of meningitis are the following: E. coli, SBHB and Klebsiella pn. Frequency of causes of meningitis changed with time. New uncommon causes have appeared. The mortality-rate remained very high.

Bacteria↗

[Monthly variation of viable count and coliforms count of sandpits in parks].

Field and experimental microbiological investigations of samples from sandpits from 5 parks were performed 2 times a month for 1 year, January-December 1990. Total viable count from the sandpits was highest in the surface layer sample than the inner layer throughout the year. However, there was no such tendency in the number of Coliforms and Enterobacter, Escherichia coli, Citrobacter. The number of bacteria on the surface and inner layer was high from April to June, and in September and October, while it was low in July and August. The proportion of Coliform bacteria represented in the total viable count ranged from 2.1 to 8.9% in the surface layer and from 1.6 to 19.6% in the inner layer. There was a significant correlation between the numbers of bacteria on the surface and inner layer. Relationships between the total viable count and Coliform count and between Coliform count and E. coli, Enterobacter and Citrobacter were also observed. In view of the results it can be concluded that park sandpits are not, from a hygienic point of view, to be an ideal environment for children to play in.

Colony Count, Microbial↗

What is the diagnostic value of beta-D-glucuronidase (BDG) activity of bacteria using Fluorocult ECD agar for their cultivation?

A total of 1510 strains from 15 genera of Gram-negative and Gram-positive bacteria were studied. More than 94% of 327 Escherichia coli strains showed beta-D-glucuronidase (BDG) activity. Seventeen serotypes from 170 E. coli O serogroup representatives were negative. Relationship between the existence of BDG positive and negative E. coli strains in the same serogroup or serotype has not been observed. The rate of BDG positivity was 42% among Salmonella arizonae strains and 42.2% among Shigella strains. Only one Citrobacter strain out of the 971 strains belonging to Citrobacter, Edwardsiella, Enterobacter, Hafnia, Klebsiella, Proteus, Serratia, Yersinia, Pseudomonas, Aeromonas, Vibrio and Listeria was BDG positive. A screening method based on only BDG activity is not sufficient for the primary diagnosis of E. coli.

Agar↗

Clinical implications of multi-drug resistance in the intensive care unit.

A prospective in vitro survey of Gram-negative isolates obtained from patients hospitalized in intensive care units in 10 Boston teaching hospitals was undertaken to document current susceptibility patterns and analyze patterns of cross-resistance. One thousand and five isolates were obtained, 18% were pseudomonas, 18% Escherichia coli, 13% klebsiella, and 22% were in the enterobacter, citrobacter, serratia group. Cross-resistance among beta-lactams and beta-lactamase inhibitors was common for species with a potential to produce the type I inducible beta-lactamase (p less than 0.01). In contrast, resistance to imipenem was not associated with cross-resistance. Ciprofloxacin and netilmicin also remained active. Clinical observations of the development of cross-resistance to the beta-lactams in enterobacter and citrobacter infections in four patients (two bacteremias and two wound infections) seen in one institution confirm these in vitro findings. Unanswered questions remain regarding the frequency of beta-lactam cross-resistance, the most likely sites of occurrence and the overall clinical significance. Clinicians should be aware of the potential selection of type-I beta-lactamase hyperproducers by the use of second or third generation cephalosporins or related beta-lactam agents.

Adult↗

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1987). III. Secular changes in susceptibility].

Sensitivity spectra of major species of bacteria (namely Escherichia coli, Klebsiella spp., Proteus spp., Citrobacter spp., Enterobacter spp., Serratia marcescens and Pseudomonas aeruginosa) which were among the clinical isolates mentioned in the first and second reports to various antibacterial and antibiotic agents and time courses of the spectra are reported below. 1. E. coli was sensitive to cefmenoxime (CMX), latamoxef (LMOX), ceftazidime (CAZ), cefzonam (CZON) and flomoxef (FMOX) which are third generation cephems, carumonam (CRMN) which is a monobactam, imipenem (IPM) which is a carbapenem, ofloxacin (OFLX) and ciprofloxacin (CPFX) which are new quinolones. Compared to the preceding 5-year period, sensitivities to most drugs have increased. 2. Klebsiella spp. were sensitive to CMX, CZON and FMOX which are third generation cephem antibiotics, CRMN which is a monobactam and gentamicin (GM) and arbekacin (HBK) which are aminoglycosides. Compared to the preceding 5-year period, the sensitivity on the whole has increased slightly. 3. Proteus spp. were sensitive to CMX, LMOX, CAZ and CZON which are third generation cephems, CRMN, a monobactam and OFLX and CPFX which are new quinolones. Compared to the preceding 5-year period, increased sensitivities, particularly to parenteral cephems, were found. 4. Citrobacter spp. were sensitive to CPFX which is a new quinolone antibiotic and CRMN, a monobactam. Compared to the preceding 5-year period, the sensitivity as a whole increased but there were still strains against which cefotiam, cefmetazole and, cefoperazone (CPZ) showed high MIC values. 5. Enterobacter spp. were sensitive to OFLX and CPFX, which are new quinolones, IPM, a carbapenem, and GM and HBK which are aminoglycosides. Compared to other bacteria, bacteria of this group were less sensitive to CPZ, CAZ, CZON, and FMOX which are third generation cephems. Compared to the preceding 5-year period, slight increases in sensitivity were found in cases of simple urinary tract infections. 6. S. marcescens as a whole was not very sensitive to antibiotics tested. Compared to the preceding 5-year period, sensitivities to CRMN and minocycline improved slightly. 7. P. aeruginosa was not very sensitive to any drug, as other bacteria were. Compared to the preceding 5-year period, sensitivities to new quinolones OFLX and CPFX and carbapenem IPM decreased slightly.

Anti-Bacterial Agents↗

[Susceptibility and R plasmids conjugation tests for 44 strains of gram negative bacilli in a burn unit].

44 strains of 9 species Gram negative bacilli were isolated and identified in a burn unit, among them 25 strains were from patients and 19 from ward environment. All strains were tested for susceptibility to antibiotics and R plasmids. Using both agar dilution and disc diffusion methods to test susceptibility to 12 kinds of antibiotics, namely, Streptomycin Chloramphenicol, Tetracycline, Ampicillin, Kanamycin, Gentamycin, Nalidixic acid, Amikacin Rifampin, Carbenicillin, Cefazolin and Polymyxin, we found that all 44 strains were susceptible to Rifampin and Polymyxin. To the other 10 kinds of antibiotics, the susceptibilities varied. 40 strains of bacteria (91%) were resistant to 3 kinds or more of antibiotics, i.e, multiple resistant bacteria, 2 strains resistant to 2 kinds of antibiotics (4.6%), and 2 strains susceptible to all 12 kinds of antibiotics (4.6%). The multiple resistant strains consisted of 9 strains (22.5%) of R plasmid-harboured bacteria, Pseudomonas aeruginosa 2 strains, Citrobacter 4 strains, Proteins 1 strain, Enterobacter aerogenes 1 strain and Escherichia coli 1 strain. All the R plasmids carried the marks of resistance to chloramphenicol, tetracycline, ampicillin, kanamycin, gentamycin, streptomycin, and carbenicillin, but no one carried marks of resistance to Cefazolin and Amikacin indicating that drug-resistance of the last two antibiotics might not be mediated by R plasmids. Two strains of Citrobacter freundii isolated from 2 patients and showing susceptibility to all antibiotics were induced to be Rifampin-resistance (Rif) strains without changing their original biological characters. They both could receive the R plasmids of the multiple resistance strains one from patient and the other from ward environment.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗

[Determination of the MIC of cefotetan against freshly isolated gram-negative bacilli].

Antimicrobial activities (MICs) of cefotetan (CTT) against 575 strains of 16 spp. of Gram-negative bacilli isolated in 1988 were determined to investigate distribution of MICs in comparison with those of cefmetazole (CMZ), cefoxitin (CFX), latamoxef (LMOX) and cefazolin (CEZ). The change in frequencies of incidence of cephem-resistant strains in the latter half of the 1980 was also investigated. Distribution of MIC of CTT varied with test strains. No or very few MICs were at or higher than 12.5 micrograms/ml at an inoculation of 10(6) cfu/ml, thus rates of CTT-resistant strains were low among Escherichia coli, Citrobacter diversus, Klebsiella spp., Proteus spp., Providencia spp., and Haemophilus influenzae. High rates of resistance to CTT were observed, however, among Citrobacter freundii, Enterobacter spp., Serratia marcescens, Morganella morganii, and Bacteroides fragilis. 2. Most CTT-resistant strains of C. freundii, Enterobacter spp. and S. marcescens were also resistant to LMOX. These resistant strains were considered to be multi-resistant strains to antibiotics including oxime type cephalosporins and monobactams. 3. Cephem-resistant E. coli was confirmed to be resistant to 22% of CEZ, 14% of CFX, 10% of CMZ and 2% of CTT tested. The incidence of cephem-resistant E. coli unconditionally showed an increasing tendency. 4. The incidence of resistant strains against cephamycins including CTT is discussed with regard to the mechanism of resistance against all beta-lactam antibiotics, and the problem of the appearance of resistant strains is close and inseparable from social background.

Cefazolin↗

[Susceptibilities of clinical isolates to antibacterial agents. A study mainly focused on ofloxacin (the second report). Reported by the Research Group for Testing ofloxacin Susceptibility on Clinical Isolates].

Susceptibilities of various clinical isolates to ofloxacin (OFLX) and other antibacterial drugs were examined at 128 hospital laboratories in 36 prefectures throughout Japan between April, 1986 and March, 1987. The results were totalized with an emphasis mainly on OFLX and were compared with data obtained in the previous year. In this study, identification and susceptibility tests of the isolates were carried out at each hospital laboratory and the tests were performed according to the 1-dilution or 3-dilution disc method in which susceptibilities are classified into 4 grades: , ++, +, and -. Similarly to the study performed in the previous year, species showing susceptibilities to OFLX included Staphylococcus aureus (4,205 strains), Staphylococcus epidermidis (2,009 strains), Entercoccus faecalis (1,697 strains), Streptococcus pneumoniae (702 strains), Escherichia coli (4,097 strains), Klebsiella pneumoniae (1,375 strains), Enterobacter cloacae (762 strains), Enterobacter aerogenes (296 strains), Citrobacter freundii (406 strains), Proteus mirabilis (613 strains), Morganella morganii (320 strains), Serratia marcescens (869 strains), Haemophilus influenzae (1,282 strains), Pseudomonas aeruginosa (4,206 strains), Acinetobacter calcoaceticus (351 strains), Acinetobacter sp. (415 strains), and Campylobacter jejuni (151 strains). Neisseria gonorrhoeae (26 strains) were exceptional due to their smaller number this time than that of the previous year and only the susceptibility to OFLX was investigated with this species. As results, OFLX showed strong antibacterial activities (similar to the previous year) against S. aureus, S. epidermidis, N. gonorrhoeae, E. coli, K. pneumoniae, E. cloacae, E. aerogenes, C. freundii, P. mirabilis, M. morganii, H. influenzae, A. calcoaceticus, Acinetobacter sp., and C. jejuni. However, when these susceptibilities shown in the present study were compared to those obtained in the previous year, many species showed decreases in the occurrence of or increases in -, though they were rather small changes. The following species were not totalized in the previous year due to their low numbers but were summarized in combination with those examined in this study: Streptococcus pyogenes (944 strains), Streptococcus agalactiae (815 strains), Enterococcus faecium (146 strains), Branhamella catarrhalis (135 strains), Citrobacter diversus (128 strains), Klebsiella oxytoca (873 strains), Proteus vulgaris (438 strains), Serratia liquefaciens (266 strains), Pseudomonas cepacia (433 strains), Pseudomonas putida (154 strains), Xanthomonas maltophilia (272 strains), Vibrio parahaemolyticus (120 strains), Bacteroides fragilis (98 strains),

Bacteria↗

Antibacterial activity of tigemonam dicholate (SQ 30836) and interaction with beta-lactamases of gram-negative bacteria.

SQ 30836 is an orally absorbed salt of tigemonam, a new monobactam similar to aztreonam in structure and microbiologic properties. When assayed against 400 clinical isolates, tigemonam's activity was similar to that of aztreonam and carumonam. It was highly effective against Enterobacteriaceae but showed poor activity against gram-positive organisms. It inhibited 90% of Escherichia coli, Klebsiella, Shigella, Yersinia, Proteus, Providencia, and Morganella strains at 0.5 micrograms/mL or less, and all Salmonella and Hafnia strains at 1 micrograms/mL or less. Citrobacter, Enterobacter, and Serratia strains were less susceptible (minimum inhibitory concentrations [MIC30] of 2, 32, and 8 micrograms/mL respectively). The activity of the new compound against Enterobacteriaceae is comparable with and often higher than that of third-generation cephalosporins and oral comparison compounds. In contrast to aztreonam, tigemonam had minimal activity against Pseudomonas sp and glucose nonfermenting gram-negative bacteria. Data suggest that poor penetration through the outer membranes of Pseudomonas sp may be responsible for this failure. Tigemonam was stable to hydrolysis by plasmid-mediated and chromosomal beta-lactamases. It was more stable than aztreonam to hydrolysis by the Kl enzyme of Klebsiella and by the Proteus vulgaris beta-lactamase. Also, measurement of the IC50 (concentration of inhibitor able to reduce the activity of the enzyme by 59%) showed that tigemonam has less affinity than aztreonam for class I cephalosporinases. However, only levels of beta-lactamase, not hydrolysis rates or affinity, correlated to MICs of the two monobactams for the resistant Enterobacter and Citrobacter strains.

Drug Interactions↗

[In vitro effect of piperacillin on aerobic bacteria. Variations according to the phenotypes of resistance to beta-lactam antibiotics].

In a first study the MICs of piperacillin (PIP), mezlocillin (MEZ), azlocillin (AZL), carbenicillin (CARB) and ticarcillin (TIC) against 563 strains of aerobic bacteria were compared. The MIC50 of PIP against E. coli and P. mirabilis was 0.5 to 1 mg/l, that is equal to those of MEZ and TIC but 2 or 3 times lower than those of AZL and CAR. The MIC50 of PIP and MEZ against Klebsiella, a species that is naturally resistant to TIC and CAR, was 4 mg/l. Enterobacter, Serratia and Citrobacter showed two populations of strains: the first was sensitive to the five penicillins tested (MIC50 of PIP: 1 to 2 mg/l); the second was resistant to all of them. PIP and AZL were more active (MIC50 8 mg/l) against Ps. aeruginosa than MEZ, TIC and CAR. All five penicillins had limited activity against Acinetobacter (MIC50 less than 16 mg/l). PIP, MEZ and AZL were more active than TIC and CAR against enterococci. In a second study, the activity of PIP was evaluated by standard sensitivity tests on 4993 strains of enterobacteria, Ps. aeruginosa and Acinetobacter classified according to their phenotype of resistance to beta-lactam antibiotics. PIP was regularly active against enterobacteria and Ps. aeruginosa strains devoid of acquired resistance. The activity of PIP was significantly reduced against enterobacteria strains with a phenotype suggesting induced penicillinase production. However, the inhibition zone diameters, although reduced, remained within what is now considered the sensitivity range (notably with E. coli and Proteus spp), which raises the problem of in vitro tests interpretation. PIP was active against E. coli strains with a "cephalosporinase" phenotype, but inactive against cefotaxime resistant strains of: Enterobacter, Citrobacter and Serratia. The activity of PIP on CAR-resistant Ps. aeruginosa strains was significantly reduced, but the inhibition zone diameter in one quarter of them was still within limits of sensitivity.

Azlocillin↗

In vitro antimicrobial activity of diethyldithiocarbamate and dimethyldithiocarbamate against methicillin-resistant Staphylococcus.

Staphylococcus aureus has appeared which is highly resistant to both methicillin and aminoglycosides. Current therapy involves long-term intravenous therapy of vancomycin. Since vancomycin is currently the only drug used to treat these patients, there is a need to develop additional antimicrobial therapy. The in vitro antimicrobial effect of the metal chelator, diethyldithiocarbamate (DDTC) and its structural analog dimethyldithiocarbamate (DMTC) were investigated. Both DDTC and DMTC were effective against S. aureus including methicillin-resistant S. aureus (MRSA). By agar diffusion, DDTC at 10 micrograms per disk produced zone sizes of 12 to 21 mm and at 100 micrograms per disk produced zone sizes of 26 to 34 mm against MRSA. The DMTC produced slightly greater zone sizes against MRSA of 16 to 24 mm and 24 to 37 mm for 10 micrograms per disk and 100 micrograms per disk, respectively. The minimum inhibitory concentration (MIC) for DMTC against MRSA was 6 micrograms per ml. Both DDTC and DMTC were also effective against enterococci, Proteus mirabilis, Klebsiella pneumoniae, Klebsiella oxytoca, Escherichia coli, Enterobacter cloacae, Enterobacter aerogenes, Salmonella species, Serratia marcescens and Citrobacter freundii at 100 micrograms per disk. The MICs of DMTC for Klebsiella pneumoniae, Klebsiella oxytoca, Escherichia coli, Salmonella and Citrobacter freundii were approximately 128 micrograms per ml while the MICs for Proteus vulgaris, Proteus mirabilis, Pseudomonas aeruginosa and Serratia marcescens was greater than or equal to 256 micrograms per ml. In addition, DMTC was synergistic with gentamicin against MRSA and coagulase-negative staphylococcus species, Enterobacter cloacae, Klebsiella pneumoniae and Pseudomonas aeruginosa. Additive and synergistic effects of DMTC were displayed with gentamicin against S. aureus including methicillin-resistant S. aureus.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗

[Comparative studies of antimicrobial agents against causative organisms isolated from urinary tract infections (1984). I. Susceptibility distribution].

Our research group was engaged for 3 years (1979-1981) in a study on sensitivities to antibiotics of 4 bacterial groups including representative pathogenic bacteria found in cases of urinary tract infections; i.e. E. coli, Klebsiella spp., Citrobacter spp., and Proteus spp. Since 1982, all the bacterial strains isolated by our group from patients with urinary tract infections and deemed by doctors in charge as pathogens were sent to the Laboratory of Clinical Pathology of Juntendo University, where they were refixed and subjected to MIC determination. This is the third year of the new study. E. coli was detected most frequently from patients with urinary tract infections and the detection frequency was 28% (323/1,153) this year (1984), whereas it was 35.3% (304/860) last year, showing a 7% decline from last year to this year. E. faecalis was next frequent organism (12.7% or 147/1,153) followed by P. aeruginosa (10.8% or 124/1,153). This order, however, was reversed from last year. Other pathogens, in a decreasing order of isolation frequencies following the above three, were as follows: Proteus spp. (9.5% or 109/1,153), S. marcescens (6.2% or 71/1,153), S. epidermidis (5.4% or 62/1,153), K. pneumoniae (4.9% or 56/1,153), Enterobacter spp. (2.4% or 28/1,153) and Citrobacter spp. (2.3% or 27/1,153). The results of the determination of the sensitivity of bacterial strains to the antibiotics are described below. Of all the oral antibacterial and antibiotic agents used against E. coli, mecillinam (MPC), cefaclor (CCL) and pipemidic acid (PPA) proved to have high antibacterial potency, and their MIC90 (the concentration to inhibit growths of 90% of the objective bacteria) was 3.13 micrograms/ml. The MIC90's of cefotiam (CTM), cefotaxime (CTX), ceftizoxime (CZX), cefmenoxime (CMX) and latamoxef (LMOX) were less than 0.39 microgram/ml. The MIC90's of cefmetazole (CMZ) and cefoperazone (CPZ) were invariably 1.56 micrograms/ml. K. pneumoniae was not sensitive to ampicillin (ABPC) and did not show much sensitivity to other oral antibacterial and antibiotic agents also. Of all the injectable preparations of antibiotics, cephem antibiotics of the third generation showed the most potent antibacterial effects against K. pneumoniae, and their MIC90's were lower than 0.10 microgram/ml for CZX, 0.20 microgram/ml for CTX, 0.39 microgram/ml for CMX, and 0.78 microgram/ml for LMOX, while MIC90's of CPZ was 6.25 micrograms/ml, which was equal to that of CMZ. The MIC90 of CTM was 0.78 microgram/ml which was identical to that of LMOX.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Bacterial Agents↗

[Antimicrobial activity of cefotiam against various clinical isolates from 1981 to 1985].

Some of new cephem antibiotics, particularly the so called the third generation cephalosporins, are reported to be potent inducers of beta-lactamases and to be responsible for developing microbial cross-resistance to multiple beta-lactam antibiotics and occasionally to the aminoglycosides (Sanders and Sanders, 1983). In Japan, third generation cephalosporins such as cefotaxime, cefoperazone, ceftizoxime, and latamoxef became available in 1981, and cefmenoxime in 1982. Therefore, it is of interest to investigate changes, if any, in the antimicrobial activity of cefotiam (CTM) against various Gram-positive and negative bacteria, particularly to determine whether its antimicrobial activity has been reduced since 1982. Susceptibilities of clinical isolates of S. aureus (1,776 strains), S. epidermidis (2,247), S. pneumoniae (160), S. pyogenes (108), E. faecalis (1,930), E. coli (2,024), K. pneumoniae (1,913), Proteus spp. (950), E. aerogenes (823), Serratia marcescens (1,160), Citrobacter spp. (303), Pseudomonas aeruginosa (2,824), and H. influenzae (396) to CTM were studied. It was found that susceptibilities of these clinical isolates to CTM were not altered from 1981 to 1985, except S. marcescens. In 1985, susceptible strains of S. aureus, S. epidermidis, S. pneumoniae, S. pyogenes and E. faecalis were 93.8, 93.4, 100, 100 and 0%, respectively. Those of E. coli, K. pneumoniae, Proteus spp., H. influenzae, P. aeruginosa, S. marcescens, E. aerogenes and Citrobacter spp. were 97.9, 97.7, 89.4, 94, 0, 10.8, 45.9 and 74.5%, respectively. The rate of susceptible strains of S. marcescens decreased from 34.7 to 10.8% since 1981 to 1985.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteria↗

[In vitro activity of a new 3d-generation cephalosporin, cefodizime, on hospital bacteria].

Minimal inhibitory concentrations (MICs) of cefodizime were evaluated by agar dilution for 746 bacterial strains isolated in two hospitals. For enterobacteriaceae MICs ranged from 0.008 micrograms/ml to more than 128 micrograms/ml (mode MIC: 0.25); mode MICs varied across species, ranging from 0.016 micrograms/ml for Proteus mirabilis to 1 microgram/ml for Citrobacter; MICs ranged from 0.12 to 8 for most Enterobacter and from 1 to 64 for Serratia. The rare cefotaxime-resistant strains, most of which were Citrobacter or Enterobacter, also showed resistance to cefodizime. Cefodizime was noticeably less active against Pseudomonas aeruginosa and Acinetobacter, with MICs ranging from 32 to more than 128. Haemophilus sp. and Gonococci, regardless of beta-lactamase-production status, as well as Neisseria meningitidis, were highly susceptible (MIC less than or equal to 0.008-0.016). Cefodizime was moderately active against methicillin-susceptible Staphylococci (MIC: 2 to 16 micrograms/ml) and failed to inhibit methicillin-resistant strains. Enterococci were slightly susceptible or resistant. Whereas the other Streptococci and Pneumococci had low MICs (0.03-0.12). A fairly wide range of MICs was found for anaerobes, with lower values for Clostridium (0.008 to 1) than for Bacteroids (8 to 128 mu g/ml). Our results show that cefodizime has the same properties as other third-generation cephalosporins: cefotaxime-resistant Enterobacteriaceae strains also exhibit resistance to cefodizime.

Bacteria↗