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[Studies on susceptibility of isolated organisms from pediatric infections against various antimicrobial agents].

Twelve oral antimicrobial agents were tested for their antimicrobial activities against causative organisms isolated from pediatric infections. Activities of these antimicrobial agents against Streptococcus pyogenes were also examined in relation to T-antigen typing of the species. The results of the investigation are summarized as follows. 1. Against Staphylococcus aureus, rokitamycin (RKM), josamycin, ofloxacin, minocycline exhibited strong antimicrobial activities, and few strains of S. aureus showed resistance to these antimicrobial agents. More strains exhibited resistance to erythromycin (EM) than to other macrolide antibiotics (MLs) examined. Amoxicillin (AMPC)-resistance was often observed also. 2. Against S. pyogenes, beta-lactam antibiotics (beta-lactams) and RKM had MIC80 of 0.20 microgram/ml or below, and no resistant strains of this organism were observed against these antibiotics. Only 2 resistant strains (2.0%) of S. pyogenes to MLs were detected, but resistance to tetracyclines (TCs) was observed at a high frequency, with 71.4% or more strains among T-4, T-6, T-12 and T-28 antigen types exhibited resistance to TCs. Among the 21 strains of T-12 antigen type examined, only one strain (4.8%) was found resistant to MLs. These observations suggested that the reduction in the frequency of ML-resistant strains was not due to the reduction in the number of T-12 antigen type strains but due to losses of resistance factors against MLs of plasmids. 3. Antibacterial activities of beta-lactams and MLs against Streptococcus pneumoniae strains were good, similarly to activities against S. pyogenes. But many strains of S. pneumoniae were resistant to TCs. 4. New quinolone antimicrobial agents (quinolones) showed excellent activities against Branhamella catarrhalis strains with EM and RKM showing the next best activities. The number of resistant strains against quinolones, however, seemed to be on an increase. 5. Quinolones had strong antimicrobial activities against Haemophilus influenzae, few strains of which showed resistance to quinolones. AMPC had the next best activity, but approximately 10% of H. influenzae exhibited resistance to this antibiotic. 6. Against Campylobacter spp., quinolones and MLs showed the best activities with MIC80 values at or below 0.25 microgram/ml, and no resistant strains of the species against these antimicrobial agents were observed. Fosfomycin and TCs showed somewhat inferior activities to quinolones and MLs, with beta-lactams showing still lower activities. 7. Only few strains of Mycoplasma pneumoniae and Chlamydia trachomatis were examined, but MLs and TCs appeared to be effective against these organisms.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Bacterial Agents↗

[Determination of antibiotype by a computer program. Epidemiological significance and antibiogram-identification correlates].

By means of a computer program disk diffusion diameter were analysed and an antibiotic susceptibility code (antibiotype) was determined for enterobacteriaceae. This code was a 6 figure-number. Each figure summarised susceptibility (susceptible or resistant) to 3 antibiotics. Thus a 18 serial antibiotics was necessary to calculate the 6 figure-code. At least following antibiotics were chosen for their characteristic behavior: amoxycillin, ticarcillin, amoxycillin + clavulanic acid, cephalothin, ticarcillin + clavulanic acid, cefotaxime, gentamycin, tobramycin, amikacin, nalidixic acid, pefloxacin, ciprofloxacin, fosfomycin and colistin. This code allowed three kind of utilisation: epidemiology by comparing biochemical and susceptibility patterns of same isolated species; laboratory control: a data base with main antibiotic susceptibility patterns for each species allowed a rapid compatibility control of biochemical identification with antibiogram. An inconsistent result lead to a checking of biochemical and susceptibility tests or to record a new code in a file to a further enrichment of the data base. Impression of a message depending of the code for a therapeutic purpose.

Drug Resistance, Microbial↗

[In vitro activity of fusidic acid in combination with various antibiotics against Staphylococcus epidermidis].

In vitro antibacterial activity of fusidic acid (FUC) in combination with cefotaxime (CTX), imipenem (IMP), gentamicin (GEN), amikacin (AKN), rifampin (RIF), fosfomycin (FOS), vancomycin, pefloxacin (PEF) was studied against 19 presumably pathogen meti-R Staphylococcus epidermidis strains. The study was carried out by means of a microtiter checkerboard method (FICs index, 19 strains) and killing-curves (3 strains). FUC x GEN, FUC x AKN and FUC x IMP combinations were found synergistic with achievable therapeutic concentrations for IMP (MIC in the combination less than 1 microgram/ml) but with higher concentrations for AKN and GEN (greater than or equal to 8 micrograms/ml). FUC x PEF combinations were regularly antagonistic. FUC x RIF, and FUC x FOS combinations showed a modal FIC greater than or equal to 4 but were found respectively additive and synergistic with killing-curve method. Remaining FUC combinations results were variable. FUC resistant mutant frequency, studied for 3 S. epidermidis strains, was similar as S. aureus one's (0.5.10(-7) a 2.5.10(-8)).

Drug Resistance, Microbial↗

[Hospital infection and resistance to antibiotics at a pediatric intensive care unit].

A retrospective study of nosocomial infection and its aetiological agents antimicrobial sensitivity in a pediatric ICU during 65 months is reported. Using statistical analysis association was found between infection site and certain diagnostic-therapeutic procedures, such as urinary infection and urinary tract catheter, respiratory lower tract infection and respiratory assistance devices, bacteremia with intravenous catheters. Also found relationship between age and causal agents: Streptococcus faecalis is the main microorganism in newborns and Pseudomonas aeruginosa in older patients. Gram negative bacilli sensitivity increased significantly for some antimicrobial drugs: carbenicillin, cefotaxime, gentamicin, fosfomycin and tobramycin, whereas gram positive microorganisms sensitivity decreased to cephalothin, cefoxitin, trimethoprim-sulphamethoxazole and gentamicin.

Anti-Bacterial Agents↗

[Serotype and susceptibilities to eight antibiotics of fifty strains of Pseudomonas aeruginosa isolated from clinical specimens and changes in susceptibilities of Pseudomonas aeruginosa to various antibiotics during a period between 1983 and 1986].

Efficacies of 8 antibiotics against Pseudomonas aeruginosa in the relation to serotypes and clinical sources were investigated on 50 strains isolated from patients at Nagoya Ekisaikai Hospital between August and September, 1986. Disk sensitivity test was carried out simultaneously for 5 antibiotics including piperacillin (PIPC), cefoperazone (CPZ), cefsulodin (CFS), ceftazidime (CAZ) and amikacin (AMK), using the single-disk method. We also examined changes in susceptibilities of P. aeruginosa to 5 antibiotics including PIPC, CFS, fosfomycin, gentamicin (GM) and AMK during last 4 years (1983-1986). The results are summarized as follows. 1. CAZ and AMK proved to have high antibacterial potencies, and their MIC80's (concentrations to inhibit growth of 80% of objective bacteria) were both 6.25 micrograms/ml. Following these two the order of potencies were; CFS, cefpiramide (CPM), PIPC, CPZ, netilmicin (NTL), and cefmenoxime (CMX). Sixty two percent of the strains of P. aeruginosa showed high resistances (MIC greater than 50 micrograms/ml) to CPM, CPZ, NTL and CFS, 58% to PIPC, and 2% to AMK. 2. With regard to serotypes, strains belonging to type E were less susceptible than those belonging to types G and I. Type E strains showed high resistance to all antibiotics except CAZ and AMK. 3. Strains obtained from pura and secreta were relatively susceptible, while those from urines were resistant, to these antibiotics tested, in general. 4. Good correlation between MIC's obtained with the agar dilution method (MIC less than or equal to 12.5 micrograms/ml) and these with the disk sensitivity test (greater than ¿ was observed. chi 2 statistical analysis showed that the results obtained with the 2 methods were closely related (P less than 0.01). 5. P. aeruginosa showed fairly high susceptibility to AMK through the recent 4 years (1983-1986). On the other hand, highly resistant strains against CFS, PIPC, FOM and GM increased rapidly during this period.

Anti-Bacterial Agents↗

[In vitro combination effects of astromicin and beta-lactam antibiotics against CFS-sensitive and CFS-resistant Pseudomonas aeruginosa. In vitro synergistic activity].

We investigated in vitro synergistic activity of astromicin (ASTM) combined with beta-lactam antibiotics (cefsulodin (CFS), cefoperazone (CPZ), ceftazidime (CAZ), piperacillin (PIPC) and fosfomycin (FOM) against fresh clinical isolated Pseudomonas aeruginosa, which consisted of 13 CFS sensitive (MIC less than or equal to 3.13 micrograms/ml) and 19 CFS resistant (MIC greater than or equal to 400 micrograms/ml) strains according to the FIC index. Against CFS-sensitive P. aeruginosa, ASTM showed good synergistic activities when combined with PIPC (54%), CAZ (38%), CPZ (23%) and CFS (8%). Against CFS-resistant P. aeruginosa, ASTM also showed high synergistic activities when combined with CAZ (63%), CPZ (47%), PIPC (37%) and CFS (11%). Among the CFS-resistant P. aeruginosa, one clinical isolate showed a high sensitivity (MIC0.78 micrograms/ml) against ASTM alone.

Aminoglycosides↗

[In vitro susceptibilities of clinical isolates of Staphylococcus aureus].

In vitro susceptibilities of 350 strains of Staphylococcus aureus to ampicillin (ABPC), methicillin (DMPPC), cloxacillin (MCIPC), cefazolin (CEZ), cefmetazole (CMZ), cefmenoxime (CMX), latamoxef (LMOX) and 5 non-beta-lactam antimicrobial agents were determined according to the standard method of Japan Society of Chemotherapy. Frequencies of the appearance of resistant organisms (MIC greater than or equal to 12.5 micrograms/ml) to beta-lactam antibiotics were 45% for ABPC, 27% for DMPPC, 11% for MCIPC, 24% for CEZ, 15% for CMZ, 36% for CMX and 51% for LMOX. To non-beta-lactam antimicrobial agents, resistant strains appeared at 31% to gentamicin, 15% to amikacin, 0.6% to minocycline (MINO), 1% to norfloxacin (NFLX) and 65% to fosfomycin (FOM). More than 80% of DMPPC-resistant strains were also resistant to LMOX, CMX, ABPC, FOM, and CEZ, but most of those were susceptible to MINO and NFLX. Incidence of DMPPC-CEZ resistant S. aureus was 23% of the 350 strains tested. As stated above, multiply resistant strains of S. aureus are present throughout different hospitals in Okinawa.

Ampicillin↗

Relationship between chemical structure of antibiotics and pharmacokinetics.

Modifications to the chemical structure of antibiotics can modify nearly all pharmacokinetic parameters: digestive absorption, half-life, protein binding, tissue distribution, metabolic biotransformation, biliary and renal elimination. Examples of increased oral bioavailability are given for beta-lactams, macrolides, tetracyclines, fosfomycin, quinolones and acyclovir. The structural modifications responsible for prolonged or shortened half-life, increased or decreased biliary excretion, increased or decreased renal clearance for the different families of antibiotics are reviewed.

Anti-Bacterial Agents↗

[Clinical observation of bacterial isolates from urine specimens of outpatients].

Changes of bacterial isolates from urine specimens of outpatients with urinary tract infections (UTI) from 1977 through 1984 were studied. Organisms which were isolated from patients with bacteriuria of over 10(3) bacteria per ml of urine regardless of grade of pyuria were studied. The incidence of UTI, especially that of acute cystitis was decreased during the recent 8 years. E. coli was the most predominant isolate in acute UTI with an isolation frequency of over 70% every year, followed by S. epidermidis nearly every year. Citrobacter spp., Klebsiella spp., P. mirabilis and S. aureus were also isolated steadily every year. Bacterial isolates in acute UTI were generally composed of these six species of bacteria. Although many kinds of bacteria were isolated in chronic UTI, E. coli was the most frequent species with an isolation frequency of 17-37%, followed by E. faecalis except in 1981 and 1982. The tendency of gram-negative rods to increase in acute and chronic UTI was observed except in 1981 and 1982. A slight decrease in sensitivity of E. coli and P. mirabilis against ampicillin (ABPC) and sulbenicillin (SBPC) was observed in acute UTI. In chronic UTI, the tendency of the sensitivity of E. coli against ABPC, SBPC and nalidixic acid to recover and the tendency of the sensitivity of P. aeruginosa against dibekacin to decrease were observed. E. faecalis was estimated to be sensitive to gentamicin, cefazolin, minocycline and fosfomycin. However, unlike those species mentioned above, many strains of E. faecalis showed a positive disc sensitivity to these drugs.

Acute Disease↗

[Detection of beta-lactamase-producing bacteria from female patients with acute uncomplicated cystitis].

A total of 122 bacterial strains isolated from urine specimens of 113 female patients with acute uncomplicated cystitis were used for the study of beta-lactamase production and their susceptibility to various antimicrobial agents was determined. Beta-Lactamase activity was qualitatively determined by a paper strip acidimetric method with benzylpenicillin as substrate and by chromogenic cephalosporin methods using pyridine-2-azo-p-dimethylaniline cephalosporin or nitrocefin as substrate. Susceptibility to antimicrobial agents, including ampicillin, carbenicillin, cephalexin, cephalothin, gentamicin, minocycline, fosfomycin, pipemidic acid and sulfamethoxazole-trimethoprim was examined by a disc method. The beta-lactamase-producing strains detected by at least one of the three tests were found in 18 of 105 Escherichia coli isolates and in the single strain of Enterobacter cloacae dermidis, 3 Enterococcus faecalis and 1 Staphylococcus aureus produced beta-lactamase. The isolation rate of strains resistant to ampicillin, carbenicillin and cephalothin in the beta-lactamase-producing strains was significantly higher than that in the non-beta-lactamase-producing strains (p less than 0.01). These results suggest that beta-lactamase plays an important role in developing resistance to beta-lactam antibiotics in patients with uncomplicated urinary tract infection as well as complicated infection.

Acute Disease↗

[Clinical evaluation of ceftriaxone in severe infections in adults].

Thirty patients (17 male, 13 female; age 17 to 84 years; normal renal function in 23 cases) with severe bacterial infections were treated with ceftriaxone. The infections was septicemia in 20 cases, a septicemia-like condition in 2 and a focal infection in 8 (2 abscesses of the lung, 2 pyelonephritis, 1 abscess of the liver, 1 subphrenic abscess, 1 meningitis developed from an abscess of the brain and 1 acute intestinal infection). 25 infections were bacteriologically documented, with recovery of the following pathogens: 20 Gram negative rods (including 10 E. coli) that were all susceptible to ceftriaxone (MIC = 0.02 to 0.5 mg/l) except 2 (1 Pseudomonas and 1 E. cloacae), 5 susceptible Gram positive cocci (3 Pneumococcus, 1 Streptococcus and 1 Staphylococcus epidermidis) and 3 susceptible anaerobes (2 B. fragilis and 1 B. melaninogenicus). Ceftriaxone was given alone in 15 cases and in association with another antibiotic in 15 cases (aminoglycoside in 10 cases, nitroimidazole in 4 and fosfomycin in 1). The dose of ceftriaxone was 1 to 2 g per day in 28 cases, 3 g per day in 1 case (meningitis with abscess of the brain) and 1 g every other day in 1 case (chronic renal failure under hemodialysis). Duration of treatment ranged from 10 to 62 days (average 17 days). The usual routes of administration were IV and IM; the SC route was used on 4 occasions. Pharmacokinetic studies of serum levels were carried out in several patients including two who had ceftriaxone subcutaneously; results were consistent with those previously reported in the literature.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Antibiotic sensitivity of Pasteurella multocida and related bacteria (bacterial groups M5 and EF4). Studies of minimal inhibitory concentrations by agar dilution].

We have been isolating Pasteurella multocida and similar germs increasingly during the last few years: due to the rabies coming back in Eastern France, more consultations have been held following animal bites; samples are then taken for a bacteriologic research. We have studied their sensitivity towards 30 antibiotics. The determination of the MIC was achieved through the agar dilution method on 34 Pasteurella multocida of human origin issued after bites and expectorations, 4 EF4 and 4 M5. The Pasteurella are very sensitive to: beta-lactam antibiotics (the lowest MIC were observed for ureido-penicillins, amino-benzylpenicillins and third generation cephalosporins), chloramphenicol, cyclines and quinolones. Fosfomycin colistin and aminoglycosides are also active but with higher MIC. The macrolides have got a slow or no activity at all. The M5 are susceptible to the same antibiotics as Pasteurella but with slightly higher concentrations. Regarding EF4, minor sensitivity or resistance to penicillin G, cephalothin and cefamandole can be pointed out.

Anti-Bacterial Agents↗

[Surgical approach to abdominal aortic aneurysm with malignant alimentary tract tumor: report of three cases].

The clinical courses of three cases with various alimentary tract malignant lesions coincidental with abdominal aortic aneurysm were reported. Of those three patients, a simultaneous resection of the malignant lesion and aneurysm was carried out in two patients, while an secondary abdominal aneurysmectomy following the resection of the malignant lesion was done in one patient. A 70-year-old man with cancer of the cecum and an infra-renal abdominal aneurysm, was diagnosed preoperatively, and a simultaneous right hemicolectomy and aneurysmectomy were carried out. In the other patient, a 77-year-old man, presence of the gastric cancer was incidentally found at laparotomy and a 75 percent gastrectomy and an aneurysmectomy were carried out. In the third patient, both gastric cancer and an abdominal aneurysm were detected preoperatively. Distal partial gastrectomy was performed first because of severe epigastralgia and an asymptomatic aneurysm. The abdominal aneurysmectomy was carried out six months later. All patients were treated by daily administration of Cefazolin sodium or cefalotin sodium (4-10 g) and Dibekacin sulfate (200 mg) for seven to ten days postoperatively. In the case of second look operation, however, Fosfomycin 2-4 g/day was added to the above mentioned drug following the aneurysmectomy. All tolerated surgery well without any signs of infections. The first patient died on the 57th postoperative day from panperitonitis carcinomatosa following an episode of intestinal obstruction. Selection of the operative approaches for patients having both an alimentary tract malignant tumor and an abdominal aortic aneurysm was difficult, although the initial surgical intervention for the more life threatening lesion would be better justified.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

[Septicemia of children in Japan (1980-1984). Part 4. Antibiotic treatment and prognosis according to causative agents].

Seven hundred and thirteen cases of septicemia whose causative organisms were detected from peripheral blood at 48 pediatric institutions throughout Japan during 1980-1984 were analyzed with respect to their chemotherapeutic outcome relative to causative microorganisms. Against Gram-positive cocci including S. pyogenes, S. agalactiae, S. viridans, S. pneumoniae, E. faecalis, penicillins (PCs) demonstrated excellent results, and cephalosporin antibiotics (CEPs) also showed good results except against E. faecalis. Combinations of PCs and aminoglycosides (AGs) resulted in a significantly high fatality rate in streptococcal infections, and very significantly high fatality rate of 38.7% in infections due to S. aureus. Combinations of CEPs and AGs showed a little lower rate than the above combinations, but monotherapy gave the best result. Infections due to S. epidermidis revealed better prognosis than those due to S. aureus. We recommend that PC II (PCase resistant) and CEP I or II should be combined with fosfomycin (FOM), if necessary, for the treatment of staphylococcal septicemia. For the treatment of septicemia due to H. influenzae, ampicillin (ABPC) is the best drug against sensitive strains and CEP IV or V may also be the drug of choice even against ABPC resistant strains. Against septicemia due to E. coli, although its prognosis is not good in general, monotherapy gave the lowest mortality. Among combined therapies, "CEPs + AGs" resulted in a significantly lower death rate of 13.3% than "PCs + AGs" which showed a death rate of 38.3%. Pseudomonas septicemia is very difficult to treat with by a monotherapy using even PC IV, CEP V or AGs any of which is effective against P. aeruginosa. However, even then, the combination of "beta-lactam + AGs" gave higher mortality than monotherapies.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminoglycosides↗

Short-course treatment of urinary tract infection.

Short-course treatment of simple cystitis is as effective as conventional 7-14 day therapy. It is less likely to cause adverse reactions or to generate bacterial resistance and is economical. Those patients who fail to respond may need further urological investigation. In short-course treatment the patient may be given a conventional dosage regimen over three days; a single conventional dose nightly for three nights; or just one massive dose. These approaches are discussed with reference to the pharmacological properties of agents available for oral administration. Clinical evidence suggests that, if the single-dose option is chosen, slowly excreted agents like trimethoprim or fosfomycin are preferable to beta-lactam agents or nitrofurantoin, which are rapidly excreted.

Anti-Bacterial Agents↗

[Virulence and enterotoxigenicity of Yersinia enterocolitica isolated from foods and other biological material].

Enterotoxigenicity, virulence and antimicrobial susceptibility were studied in thirteen strains of Yersinia enterocolitica isolated from meat foods and organs of slaughtered animals. The following biotypes (B), serotypes (O) and lisotypes (Lis) were studied: B2, O:9, Lis X3 and B1, O:7,8, Lis Xo (from thick fresh sausages); B1, O:5, Lis Xz (from slender sausages); B1, O:5, Lis Xz and B2, O:9, Lis X3 (from bovine tongues); B1, O:6, Lis Xz (from porcine tongues) and B1, O:6, Lis Xz (from porcine caeca) (Table 1). Virulence was determined by i) the autoagglutination test (Laird and Cavanaugh), replacing in the Eagle medium amino acids and vitamins with proteose peptone (1%), tryptone (1%) and yeast extract (0.5%), and ii) the calcium dependency test. The LD50 of five strains was determined by i.p. injection of O.5 ml of cell suspensions into white mice and estimated by the Spearman Kärber method. LD50 varied from 2 x 10(9) to 7 x 10(9) viable cells per ml. The enterotoxigenicity test was carried out in suckling white mice and the invasiveness test (Sereny) in adult white mice. Two strains showed autoagglutination, five calcium dependency, two were invasive and eight produced enterotoxin. Antimicrobial susceptibility was assayed by the modified Kirby and Bauer test. All the strains were susceptible to kanamycin, amikacin, cefotaxime, cefuroxime, chloramphenicol, fosfomycin, mezlocillin, nitrofurantoin, piperacillin, piperimidic acid, polymyxin B, sisomycin and tobramycin, and resistant to cephalotoxin, ampicillin and trimethoprim-sulfamethoxazole.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Metronidazole pharmacokinetics in perilymph, aqueous humor and cerebrospinal fluid].

Since metronidazole is very effective against anaerobic bacteria, we studied its pharmacokinetics in perilymph, cerebrospinal fluid, aqueous humour, and serum. 1, 2, 4, 6, 10 and 16.5 hours after intraperitoneal injection of 200 mg/kg metronidazole to six groups of six guinea pigs each, we determined the drug concentrations by high-pressure liquid chromatography. In the serum, 1, 2 and 16.5 hours after application, drug levels of 194 +/- 22 mg/l, 127 +/- 54 mg/l and 2 +/- 1 mg/l respectively were found. Half-life was 6 hours. Similar high and long-lasting concentrations could be determined in the aqueous humour, cerebrospinal fluid and perilymph. In contrast to our findings with aminoglycoside antibiotics, beta lactam antibiotics and fosfomycin, we could not observe any retention of metronidazole in the perilymph.

Animals↗

[Infection of the valves of CSF shunts. Results of local and general antibiotic treatment in 6 cases].

Infection of six cerebro-spinal fluid shunts in six patients were treated with daily intrashunt injections of antibiotics plus combination of intravenous or oral systemic antibiotic therapy. Three organisms were involved in the shunt infection: staphylococcus epidermidis in five, staphylococcus capitis and micrococcus varians. One patient had mixed shunt infection with micrococcus varians and staphylococcus épidermidis. All six patients received daily intrashunt injections of vancomycin and oral rifampin with a combination of trimethoprim/sulfamethoxazole (three patients), or intravenous fosfomycin (two patients), or intravenous vancomycin (one patient). Four of six cases were considered cured of their infection without shunt surgery. Their hydrocephalus will be well controlled during antibiotic therapy. Surgery was necessary for two patients with associated shunt malfunction, one of them was considered a treatment failure of antibiotic therapy.

Adult↗