Micronucleus assays using cytochalasin-blocked MCL-5 cells, a proprietary human cell line expressing five human cytochromes P-450 and microsomal epoxide hydrolase

A total of 100 S. hyicus strains isolated from healthy piglets and piglets with exudative epidermitis originating from 100 different herds was examined for drug-resistance and prevalence of plasmids. Resistance to macrolide/linosamide antibiotics could be related to plasmids in 55 (93%) of the 59 resistant strains: A plasmid of 2.4 kb mediating resistance to macrolides and lincosamides was observed in 25 strains, and a plasmid of 11.5 kb mediating resistance to both macrolides/lincosamides and tetracycline was observed in 30 strains. A plasmid with a molecular weight of 4.5 kb was shown by curing experiments to be associated with resistance to tetracycline in 12 strains. All together, 47 strains were resistant to tetracycline. In 42 (89%) of these strains tetracycline-resistance was found to be encoded by plasmids. Fifty six strains were resistant to streptomycin, and resistance was associated with the presence of a 4.4 kb plasmid in 17 strains studied. Resistance to penicillin, observed in 44 strains, and resistance to kanamycin, observed in 15 strains, could not be related to plasmids in any of these strains. The 11.5 kb plasmid was observed in 39% of the strains isolated from piglets with EE, and in 7% of the strains isolated from healthy piglets. Despite its higher prevalence in strains from piglets with EE, the 11.5 kb plasmid could not be shown to encode production of capsule or exfoliative substances: factors which might play a role in the development of exudative epidermitis in piglets.     

Visual motion aftereffects: differential adaptation and test stimulation

Cefditoren (formerly ME-1206), a new orally administered cephalosporin, was evaluated in vitro against 1249 recently isolated strains of Streptococcus pneumoniae (500 strains), Moraxella catarrhalis (250 strains), and Haemophilus influenzae (499 strains). Reference National Committee for Clinical Laboratory Standards methods were used and the strains were representative for the current rates of beta-lactamase production or penicillin resistance. Cefditoren had MIC50/MIC90 results for Moraxella catarrhalis and Haemophilus influenzae of 0.12/0.5 and < or = 0.008/0.015 microgram/mL, respectively. The pneumococci were consistently twofold to eightfold more susceptible to cefditoren than other oral cephalosporins or penicillins. The MIC90 for penicillin-resistant S. pneumoniae was only 2 micrograms cefditoren/mL, and the highest recorded MIC was 4 micrograms/mL. Cefditoren appears to be a very promising beta-lactam possessing the greatest potency and potential spectrum versus contemporary (1997) respiratory tract pathogens.     

Characterization of plasmids which mediate resistance to multiple antibiotics in gram-negative bacteria of nosocomial origin

BACKGROUND: The genetic and molecular mechanisms involved in antimicrobial resistance of 10 strains of gramnegative bacilli (1 Serratia marcescens; 2 Escherichia coli; 1 Proteus mirabilis; 4 Klebsiella pneumoniae; 1 Enterobacter cloacae y 1 Alcaligenes faecalis), isolated from adult patients with nosocomial pulmonary infection at the in-patient facilities of the University Hospital of Los Andes, Mérida, Venezuela, have been studied. METHODS: The antimicrobial susceptibility was determined by minimum inhibitory concentrations using the dilution method in agar. The study of extrachromosomal genes was carried out by conjugation, bacterial infection with the bacteriophage M13 and curing of plasmid by acridine orange. The plasmids were isolated by alkaline lysis and analysis of restriction endonuclease digestion was carried out separately using the enzymes EcoRI and HindIII. A DNA probe, derived from the region which encodes the TEM-1 beta-lactamase of the plasmid pBR322 was used for dot-blot hybridization tests. RESULTS: All of the gramnegative bacilli showed resistance to ampicillin, carbenicillin and cephalothin (> 128 micrograms/ml) and 3 strains also showed resistance to gentamicin (> 64 micrograms/ml). Genetic and molecular procedures showed the presence of conjugative plasmids of approximately 54 kb in all the 10 strains. The restriction patterns obtained by using EcoRI and HindIII indicated common DNA fragments in most of the plasmids studied. The dot-blot hybridization tests confirmed homology between the plasmids and the DNA probe used (TEM-1 beta-lactamase). CONCLUSIONS: In this study, the gramnegative bacteria of nosocomial origin harbored self-transferable plasmids of approximately 54 kb, which mediate resistance to gentamicin and encode a beta-lactamase of the TEM group.     

Antimicrobial activity of carbapenem antibiotics against gram-negative bacilli

Antimicrobial activities of meropenem (MEPM), imipenem (IPM), panipenem (PAPM), ceftazidime (CAZ), cefozopran (CZOP), aztreonam (AZT), norfloxacin (NFLX) and tetracycline (TC) against clinically isolated Gram-negative bacilli [271 strains of Enterobacteriaceae and 242 strains non-fermentative Gram-negative bacteria (NFB)] were investigated. Among carbapenem antibiotics, MEPM showed the lowest MIC90, which activity was about four-hold higher than those of IPM and PAPM. The activity of IPM was equal or slightly superior to that of PAPM. Resistance to IPM (> 16 micrograms/ml) was observed in 3 strains of Enterobacteriaceae (1.1%) and 14 strains of NFB (5.8%). It is conceivable that these strains produce metallo-beta-lactamase. Referring to the correlation among MICs of MEPM, IPM and PAPM, 3 strains in 3 species of Enterobacteriaceae showed cross resistance to carbapenems; while 14 strains of NFB showed cross resistance to MEPM and IPM, 15 strains to MEPM and PAPM, and 29 strains to IPM and PAPM, and all of these strains were Pseudomonas aeruginosa. Fifteen of 29 strains of IPM-resistant and 77 of 92 strains of PAPM-resistant P. aeruginosa were susceptible to MEPM. Thirty-three strains (12%) of the Enterobacteriaceae were resistant to CAZ and AZT (> or = 32 micrograms/ml) and these were considered as ESBL-producing strains.     

A case report of extensive vitiligo

Minimum inhibitory concentrations of doxycycline and oxytetracycline were determined against 55 Pasteurella multocida strains, 59 Actinobacillus pleuropneumoniae strains and 26 Mycoplasma hyopneumoniae strains isolated from the respiratory tract of pigs. An additional set of 76 P multocida strains isolated from pneumonic pigs was tested for their minimum inhibitory concentrations of doxycycline. The P multocida and A pleuropneumoniae strains were isolated in France and the minimum inhibitory concentrations were determined by an agar dilution method. The M hyopneumoniae strains were isolated in the United Kingdom and minimum inhibitory concentrations were determined by a serial broth dilution method. All the strains tested were susceptible to doxycycline whereas 15 per cent of the P multocida strains and 22 per cent of the A pleuropneumoniae strains were resistant to oxytetracycline. Doxycycline concentrations inhibiting 90 per cent of strains were 1 microgram/ml for P multocida and 2 micrograms/ml for A pleuropneumoniae. The ratio of the minimum inhibitory concentrations of doxycycline and oxytetracycline ranged between 1/1 and 1/4 for the oxytetracycline-susceptible strains and between 1/16 and 1/64 for the oxytetracycline-resistant strains. All the M hyopneumoniae strains were susceptible to doxycycline and oxytetracycline, the concentrations inhibiting 90 per cent of strains being 1 microgram/ml and 2 micrograms/ml, respectively. These data confirm that doxycycline has a higher in vitro activity against pig respiratory pathogens than oxytetracycline.     

Esophago-jejuno-gastroplasty in the treatment of peptic stenosis of the esophagus]

Resistance to benzalkonium chloride (BC) among Pseudomonas spp. isolated from poultry carcasses was determined and strategies for elimination of resistant strains evaluated. This investigation showed that resistance was quite common, about 30% of the isolates being able to grow in 200 micrograms ml-1 BC. Pseudomonas fluorescens strains were generally less susceptible than strains of Ps. lundensis and Ps. fragi. An overnight incubation in medium containing 200 micrograms ml-1 BC was sufficient to reduce the susceptibility of two Pseudomonas strains to the lethal effect of BC significantly. Adding EDTA enhanced the lethal effect of BC, but the effect was reduced after growing cells in medium containing BC and EDTA. Growth in medium with a quaternary ammonium compound (QAC) rendered the cells more susceptible to chlorine, phenolics, and alkylaminoacetate. These results indicate that alternating use of QACs with these compounds can be used to avoid build-up of resistant strains. In addition, increased temperatures improved the lethal effect of BC and should be considered when planning disinfection routines.     

Antibiotic susceptibility to microorganisms isolated in blood cultures of patients an the Ignacio Chavez National Institute of Cardiology

A microdilution method was utilized for determining susceptibility to several antimicrobial agents in 142 bacterial blood culture isolates obtained during a one year period. Associated clinical features were also identified. Three cases of polymicrobial bacteriemia were found. Endocarditis was the most frequent source of bacteriemia (28.5%) and the viridans streptococci were the most frequently isolated microorganism (53%). Surprisingly, half of the bacteriemic episodes corresponded to a nosocomial infection most of which were due to staphylococci (25%) and Enterobacter sp (22%). Viridans streptococci group were 61.5% resistant to penicillin (MIC > 0.12 micrograms/mL). These strains also showed a 31% resistance to ceftriaxone (MIC > 8 micrograms/mL). The staphylococcal strains showed a 19% resistance to oxacillin; this resistance occurred for coagulase negative staphylococcis in 32% (6/19) and for S. aureus in 9% (2/22). All Gram-positive microorganisms were susceptible to vancomycin. The enterobacteria group were susceptible to most antimicrobial agents; nevertheless this group showed a 45% resistance to amikacin. In contrast, the non enterobacteria group were resistant to most of the antimicrobial agents tested except to imipenem, ceftazidime and ciprofloxacin. When comparing susceptibility longitudinally, no significative changes were identified, but a significant increase was found in MIC50-90 to amikacin and cephalothin when testing S. aureus, and cefoperazone in the non enterobacteria group.     

Norepinephrine loss selectively enhances chronic nigrostriatal dopamine depletion in mice and rats

A total of 3,700 Pseudomonas aeruginosa isolates were collected from 17 general hospitals in Japan from 1992 to 1994. Of these isolates, 132 carbapenem-resistant strains were subjected to DNA hybridization analysis with the metallo-beta-lactamase gene (blaIMP)-specific probe. Fifteen strains carrying the metallo-beta-lactamase gene were identified in five hospitals in different geographical areas. Three strains of P. aeruginosa demonstrated high-level imipenem resistance (MIC, > or = 128 micrograms/ml), two strains exhibited low-level imipenem resistance (MIC, < or = 4 micrograms/ml), and the rest of the strains were in between. These results revealed that the acquisition of a metallo-beta-lactamase gene alone does not necessarily confer elevated resistance to carbapenems. In several strains, the metallo-beta-lactamase gene was carried by large plasmids, and carbapenem resistance was transferred from P. aeruginosa to Escherichia coli by electroporation in association with the acquisition of the large plasmid. Southern hybridization analysis and genomic DNA fingerprinting profiles revealed different genetic backgrounds for these 15 isolates, although considerable similarity was observed for the strains isolated from the same hospital. These findings suggest that the metallo-beta-lactamase-producing P. aeruginosa strains are not confined to a unique clonal lineage but proliferated multifocally by plasmid-mediated dissemination of the metallo-beta-lactamase gene in strains of different genetic backgrounds. Thus, further proliferation of metallo-beta-lactamase-producing strains with resistance to various beta-lactams may well be inevitable in the future, which emphasizes the need for early recognition of metallo-beta-lactamase-producing strains, rigorous infection control, and restricted clinical use of broad-spectrum beta-lactams including carbapenems.     

A fatal drug interaction between clozapine and fluoxetine

A case is presented of a fatal drug interaction caused by ingestion of clozapine (Clozaril) and fluoxetine (Prozac). Clozapine is a tricyclic dibenzodiazepine derivative used as an "atypical antipsychotic" in the treatment of severe paranoid schizophrenia. Fluoxetine is a selective serotonin reuptake inhibitor used for the treatment of major depression. Clinical studies have proven that concomitant administration of fluoxetine and clozapine produces increased plasma concentrations of clozapine and enhances clozapine's pharmacological effects due to suspected inhibition of clozapine metabolism by fluoxetine. Blood, gastric, and urine specimens were analyzed for fluoxetine by gas chromatography/mass spectrometry (GC/MS) and for clozapine by gas-liquid chromatography (GLC). Clozapine concentrations were: plasma, 4.9 micrograms/mL; gastric contents, 265 mg; and urine, 51.5 micrograms/mL. Fluoxetine concentrations were: blood, 0.7 microgram/mL; gastric contents, 3.7 mg; and urine 1.6 micrograms/mL. Norfluoxetine concentrations were: blood, 0.6 microgram/mL, and none detected in the gastric contents or urine. Analysis of the biological specimens for other drugs revealed the presence of ethanol (blood, 35 mg/dL; vitreous, 56 mg/dL; and urine 153 mg/dL) and caffeine (present in all specimens). The combination of these drugs produced lethal concentrations of clozapine and high therapeutic to toxic concentrations of fluoxetine. The deceased had pulmonary edema, visceral vascular congestion, paralytic ileus, gastroenteritis and eosinophilia. These conditions are associated with clozapine toxicity. The combined central nervous system, respiratory and cardiovascular depression of these drugs was sufficient to cause death. The death was determined to be a clozapine overdose due to a fatal drug interaction.     

In vitro antimicrobial activity of fluoroquinolones against clinical isolates obtained in 1989 and 1990

The in vitro activity of nine fluoroquinolones, enoxacin, norfloxacin, ofloxacin, ciprofloxacin, lomefloxacin, tosufloxacin, sparfloxacin, fleroxacin and levofloxacin, and two earlier quinolones, nalidixic acid and pipemidic acid, against 1,346 bacterial strains isolated clinically between 1989 and 1990, was evaluated by agar dilution method. The bacteria studied were Staphylococcus aureus (including methicillin-susceptible and -resistant strains), Staphylococcus epidermidis, Enterococcus species (including high-level gentamicin-resistant strains), Escherichia coli, Salmonella species, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, Citrobacter spp., Pseudomonas aeruginosa, Pseudomonas cepacia, Acinetobacter baumannii, and Bacteroides fragilis. In contrast to the moderate to poor activity of two earlier quinolones, the fluoroquinolones acted well against most Enterobacteriaceae and A. baumannii. The minimum inhibitory concentrations for 90% of the drug strains (MIC90s) were < 1 microgram/mL against most tested species. Ciprofloxacin, tosufloxacin, sparfloxacin, and levofloxacin were more effective against multi-drug-resistant nosocomial pathogens. All fluoroquinolones assayed were very active against methicillin-susceptible S. aureus, with MIC90s < or = 1 microgram/mL. For methicillin-resistant strains, on the other hand, the MIC90s were > or = 4 micrograms/mL. There was no significant difference in fluoroquinolone susceptibility between methicillin-susceptible and -resistant S. epidermidis. Sparfloxacin, tosufloxacin, ciprofloxacin and levofloxacin were more active against enterococci. Most fluoroquinolones were relatively inactive against B. fragilis, with the exception of tosufloxacin, sparfloxacin and levofloxacin. The MIC90s of most quinolones assayed against K. pneumoniae, Citrobacter spp., E. cloacae, S. aureus and S. epidermidis were at least four-fold higher in our study. Therefore, it is important for physicians to use fluoroquinolones carefully so as to prevent or delay the emergence of resistant strains.     

Resistance to tetracycline of E. coli of chicken intestines after prophylactic treatment of animal feed with bioptivet GB

This study describes the influence of bioptivet GB on minimum inhibitory concentrations (MIC) for oxytetracycline (OTC) of the intestinal E. coli flora of young broiler chickens after oral administration at a dosage equivalent to a prophylactic course of treatment. From day 6 until day 15 one group of 50 birds received a diet containing 124 ppm OTC, another group of 75 birds served as non medicated control. Investigated E. coli had been isolated from cloacal swabs and from caecal contents. MIC of 1581 E. coli strains were determined by agar dilution test procedures. MIC of OTC for the investigated strains were either > or = 128 micrograms/ml (resistant) or < or = 4 micrograms/ml (susceptible). Even from undosed birds resistant strains were isolated frequently, especially from samples of caecal contents. Administration of bioptivet GB resulted in a statistically significant increase in the average MIC. Statistically higher average MIC were recorded among isolates from cloacal swabs only during application of the drug. For strains from caecal contents this could be demonstrated until the end of the experiment.     

Enterococcus faecium: in vitro activity of antimicrobial drugs, singly and combined, with and without defibrinated human blood, against multiple-antibiotic-resistant strains

The minimal inhibitory (MICs) and bactericidal concentrations of 14 antimicrobial drugs were determined against 17 clinical isolates of Enterococcus faecium, including 4 glycopeptide-resistant strains. Both teicoplanin and vancomycin lacked bactericidal activity against all 13 susceptible isolates. Time-kill experiments served to test various antibiotic combinations chiefly against glycopeptide-resistant strains in Mueller-Hinton broth (MHB) and in MHB supplemented with 65% (v/v) fresh defibrinated human blood. Co-trimoxazole, fusidic acid, and novobiocin yielded bacteriostatic effects. Rifampin was bactericidally active against rifampin-susceptible strains (MICs = 0.125 micrograms/ml), but less so against low-level-rifampin-resistant (MICs = 2-8 micrograms/ml) strains in MHB. However, in the presence of human blood, rifampin (2 micrograms/ml) combined with co-trimoxazole (0.25/4.75 micrograms/ml) killed rifampin-susceptible and low-level-rifampin-resistant, but not moderate-level-rifampin-resistant (MICs = 16-32 micrograms/ml) strains of E. faecium. Of two topical drugs examined, mupirocin merely inhibited strains of E. faecium; conversely, taurolidine at 2,000 micrograms/ml was efficacious against all strains examined, although the kinetics of bactericidal activity were retarded somewhat in the presence of 65 vol% human blood.     

Does in vitro susceptibility to rifabutin and ethambutol predict the response to treatment of Mycobacterium avium complex bacteremia with rifabutin, ethambutol, and clarithromycin? Canadian HIV Trials Network Protocol 010 Study Group

The in vitro susceptibilities of baseline Mycobacterium avium complex (MAC) blood isolates from 86 patients with AIDS who were treated with clarithromycin, ethambutol, and rifabutin were determined to examine whether these results predict bacteriologic response to treatment. No patient received prior prophylaxis with clarithromycin or azithromycin. Minimum inhibitory concentrations (MICs) of clarithromycin for all isolates were < or = 2 micrograms/mL. The median MIC of rifabutin was between 0.25 and 0.5 microgram/mL, and all isolates were susceptible to < or = 2 micrograms of rifabutin/mL. The median MIC of ethambutol was 4 micrograms/mL, and the MIC90 was 8 micrograms/mL. There was no correlation between ethambutol susceptibility and subsequent bacteriologic clearance. At all time points through week 12, bacteriologic clearance occurred more frequently in patients with isolates for which MICs of rifabutin were lower, but this difference was statistically significant only at week 2. Susceptibility testing for baseline MAC isolates from AIDS patients not previously treated with clarithromycin or azithromycin does not appear to be useful in guiding therapy.     

Isolated single-lung perfusion with TNF-alpha in a rat sarcoma lung metastases model

We conducted a trial of isolated lung perfusion using tumor necrosis factor (TNF) in an experimental sarcoma lung metastasis model. In an in vitro experiment, methylcholanthrene-induced sarcoma cells were incubated for 48 hours with 42 micrograms/mL of either human or murine TNF. Controls were incubated with Hank's balanced salt solution. In an in vivo experiment, 23 F344 rats were injected with 10(7) methylcholanthrene-induced sarcoma cells. On day 7, 4 animals were perfused with 210 micrograms of murine TNF, 5 animals were perfused with 420 micrograms of murine TNF, 10 animals underwent isolated lung perfusion with 420 micrograms of human TNF, and 4 animals were injected systemically with 420 micrograms of human TNF. Animals were sacrificed on day 14 and the lung nodules counted. The cells incubated with murine TNF exhibited a 21% decrease in growth (p = 0.07); cells incubated with human TNF showed a 37% decrease in growth (p < 0.05). Animals perfused with 210 micrograms/mL of murine TNF and animals treated by systemically administered human TNF showed no tumor response. Animals perfused with 420 micrograms/mL of murine TNF had 7.8 +/- 14.2 nodules on the left lung and 58.5 +/- 66.0 nodules on the right lung (p = 0.07). Animals perfused with 420 micrograms/mL of human TNF had 21.7 +/- 18.3 nodules on the left lung and 91.7 +/- 66.2 nodules on the right lung (p < 0.01). On the basis of these findings, we conclude that isolated lung perfusion with TNF can be done safely in the rat and is effective in decreasing the growth of sarcoma lung metastases.     

Isolation of penicillin-resistant Streptococcus pneumoniae in Saga Medical School Hospital

A recent nationwide increase in beta-lactams-resistant Streptococcus pneumoniae has attracted a great deal of attention. We studied the drug sensitivity of S. pneumoniae isolated from various clinical specimens in Saga Medical School Hospital between April 1988 and December 1991. To determine the drug sensitivity of the strains, we used a micro-dilution method and determined the MIC. Drug resistance was evaluated using MIC of ampicillin (ABPC) as a reference MIC, and the results were roughly classified into the following three groups: sensitive (< or = 0.1 microgram/ml), moderately resistant (0.2-3.13 micrograms/ml) and highly resistant (> or = 6.25 micrograms/ml). The isolation frequency was calculated on the basis of one strain from one patient. No strain of S. pneumoniae with high resistance against ABPC was found in 1988 (94 strains of S. pneumoniae were isolated) and 1990 (115 strains isolated), but one such strain (0.8%) was found among 129 strains isolated in 1989, and 2 such strains (2.4%) among 84 strains isolated in 1991. Moderately resistant strains were isolated at the frequencies of 12.8%, 15.5%, 22.6%, and 21.4% respectively, in 1988, 1989, 1990, and 1991. A sum of the frequencies of "moderately resistant" and "highly resistant" (2.4%) strains was 23.8% in 1991. The frequency of resistant strains is increasing and the intensity of resistance is also being elevated.     

A pharmacodynamic approach to the estimate of carbamazepine autoinduction

Population-based pharmacokinetic prediction algorithms have been developed for several medications. A fundamental assumption has been that the kinetics remain constant over time. Carbamazepine (CBZ), however, induces its own metabolism in a concentration- and time-dependent manner. A Bayesian estimation program is presented that models the changing catabolic enzyme activity, linearly related to hepatic microsomal enzyme concentration, along with the serum drug concentration. An Emax model is used for enzyme formation with respect to drug concentration: elimination of enzyme activity is modeled as a first-order process. This program was tested in 22 drug-naive outpatients begun on CBZ monotherapy. The 1 week concentrations were used to prospectively predict concentrations at 1 month of therapy and were very close to actual measurements: prediction bias (mean error of prediction) = -0.1 micrograms/mL and precision (median absolute error of prediction) = 1.2 micrograms/mL. Comparison estimates, made by assuming a constant concentration/dose ratio, had bias = 2.6 micrograms/mL (p < 0.001) and precision = 2.2 micrograms/mL (p = 0.01). We conclude that (1) CBZ autoinduction is not complete after 1 week of therapy and (2) the methodology permits accurate estimation of CBZ pharmacokinetics.     

Methimazole and propylthiouracil equally cross the perfused human term placental lobule

Propylthiouracil (PTU) is widely believed to cross the placenta less freely than methimazole (MMI) and is therefore regarded as the preferred drug for treatment of hyperthyroidism in pregnancy. Clinical studies comparing the two drugs show, however, no differences in maternal or fetal thyroid function. We investigated transfer from the maternal to the fetal circuit in the isolated perfused term human placental lobule of low and high doses of PTU (4 micrograms/mL and 40 micrograms/mL) and MMI (1.5 micrograms/mL and 15 micrograms/mL) in protein-free perfusate and low doses of both drugs with addition of 40 g/L of bovine albumin. Both drugs readily crossed the placenta, reaching equilibrium in all experiments in about 2 h. Drug concentrations in the two circuits fitted a two compartmental model. Transfer kinetics for the two drugs were similar, nonsaturable, and unaffected by addition of albumin. Clearances (mL.min-1.g-1, means +/- SD) of PTU from maternal to fetal circuits were: 0.229 +/- 0.110, 0.216 +/- 0.065, and 0.170 +/- 0.032; and for transfer of MMI: 0.165 +/- 0.025, 0.232 +/- 0.153, and 0.174 +/- 0.009 (for low doses without, low doses with, and high doses without albumin, respectively). Clearances of PTU from fetal to maternal circuits were: 0.147 +/- 0.072, 0.109 +/- 0.014, and 0.116 +/- 0.028; and for transfer of MMI: 0.095 +/- 0.029, 0.122 +/- 0.088, and 0.12 +/- 0.005 (in the same experiments). There was no significant difference between drugs or drug doses and no effect of addition of albumin. We conclude that PTU and MMI have similar placental transfer kinetics.     

Fluconazole-resistant recurrent oral candidiasis in human immunodeficiency virus-positive patients: persistence of Candida albicans strains with the same genotype

Thirty human immunodeficiency virus-positive patients carrying Candida albicans in their oropharynx were treated with fluconazole and were monitored for 90 to 570 days. Fluconazole-resistant C. albicans (MIC, > 32 micrograms/ml) appeared only in seven patients and only after 90 days of treatment corresponding to a total dose of more than 10 g. Resistance was not associated with resistance to other azole derivatives. Susceptible and resistant strains from each patient had the same genotype (as defined by electrophoretic karyotype and restriction fragment length polymorphism). Thus, the resistant strains were selected by the antimycotic treatment from the susceptible strain present in each case.     

Relationship between streptomycin susceptibility and rpsL mutations of Mycobacterium tuberculosis strains

The relationship between streptomycin (SM) susceptibility and rpsL mutations of Mycobacterium tuberculosis strains was studied. Of 18 clinically isolated SM-resistant M.tuberculosis strains, mutation was suspected in 9 strains (50%) with SM MICs of > or = 256 micrograms/ml by PCR-single strand conformation polymorphism targeting rpsL gene. On the other hand, using PCR-direct sequence method, amino acid substitution caused by single nucleotide point mutation in rpsL gene was demonstrated in 11 out of 18 strains (61%). The same amino acid substitution at codon 43 (Lys-->Arg) was observed in all 11 strains with SM MICs of > or = 256 micrograms/ml. In addition, PCR products obtained from these 11 strains could not be cut by a restriction enzyme, Mbo II, while H37Rv strain and the other 32 strains with SM MICs of < 256 micrograms/ml were cut into 2 fragments. In conclusion, our results suggest that highly SM-resistant M.tuberculosis strains with MICs of > or = 256 micrograms/ml could be rapidly and easily detected by the restriction enzymatic method.     

Predation of livestock ticks by chickens as a tick-control method in a resource-poor urban environment

The increasing prevalence of streptococci as causes of potentially fatal nosocomial bacteremia requires that antimicrobial agents used for empiric therapy in hospitalized patients include both pneumococci and viridans group streptococci as well as beta-hemolytic streptococci in their activity profile. In this study, the in vitro activity of cefepime, a new fourth-generation cephalosporin, was compared with other cephalosporins versus 197 nosocomial blood stream isolates of streptococci (20 Streptococcus pneumoniae, 104 viridans group, and 73 beta-hemolytic) isolated from patients at more than 30 medial centers from 1995 to 1997. Additional agents tested included penicillin, erythromycin, and vancomycin. Overall, cefepime inhibited 83% of the isolates at concentrations < or = 0.5 microgram/mL and 100% at < or = 8 micrograms/mL. By comparison, ceftazidime inhibited 35 and 88% of isolates at the same concentrations. Cefepime was approximately eightfold more potent than ceftazidime against S. pneumoniae, viridans group streptococci, and beta-hemolytic streptococci. Among the 42 isolates with penicillin MICs > 0.12 microgram/mL, 100% were inhibited by cefepime and only 48% by ceftazidime at < or = 8 micrograms/mL. The rank order of activity for all six agents against the 197 isolates was vancomycin > ceftriaxone > cefepime > penicillin > erythromycin > ceftazidime. Based on the results of the present study, cefepime and ceftriaxone were the superior cephalosporins in potency and spectrum for empiric coverage of patients at risk for streptococcal blood stream infections.