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Influence of sublethal concentrations of antibiotics on the expression of the mannose-specific ligand of Escherichia coli.

The ability of streptomycin, in subinhibitory concentrations, to differentially suppress the acquisition of the mannose-binding activity of Escherichia coli was demonstrated in several strains, but not one with a ribosomal mutation to high-level streptomycin resistance, rpsL. We also determined that the growth of bacteria in other antibiotics, notably those that interfere with protein synthesis, resulted in diminished mannose-binding activity (as measured by yeast cell agglutination), degree of piliation (as measured by electron microscopy), and adherence to human oral epithelial cells. The aminoglycoside antibiotics streptomycin, gentamicin, and neomycin had the most marked effects relative to their minimum inhibitory concentrations, followed by tetracycline. Both spectinomycin and chloramphenicol had more effect on adherence than on piliation, although spectinomycin had a more pronounced effect on mannose-binding activity than did chloramphenicol. We conclude that antibiotics, at concentrations below their minimum inhibitory concentration, may have profound effects on surface properties of bacteria that may be pertinent for their ability to colonize and infect human mucosal surfaces. The mechanism(s) may vary from one drug to another, but appear to depend on the classic actions of the antibiotics on inhibiting protein synthesis.

Anti-Bacterial Agents↗

aadA confers streptomycin resistance in Borrelia burgdorferi.

To enhance genetic manipulation of the Lyme disease spirochete Borrelia burgdorferi, we assayed the aadA gene for the ability to confer resistance to the antibiotics spectinomycin and streptomycin. Using the previously described pBSV2 as a backbone, a shuttle vector, termed pKFSS1, which carries the aadA open reading frame fused to the B. burgdorferi flgB promoter was constructed. The hybrid flgB promoter-aadA cassette confers resistance to spectinomycin and streptomycin in both B. burgdorferi and Escherichia coli. pKFSS1 has a replication origin derived from the 9-kb circular plasmid and can be comaintained in B. burgdorferi with extant shuttle vector pCE320, which has a replication origin derived from a 32-kb circular plasmid, or pBSV2, despite the fact that pKFSS1 and pBSV2 have the same replication origin. Our results demonstrate the availability of a new selectable marker and shuttle vector for genetically dissecting B. burgdorferi at the molecular level.

Anti-Bacterial Agents↗

Disk diffusion method for susceptibility testing of Neisseria gonorrhoeae.

The standard medium for disk diffusion and MIC testing of Neisseria gonorrhoeae (that of the National Committee for Clinical Laboratory Standards) was tested to establish zone correlations for the MIC breakpoints currently used in Sweden. Eight gonococcal control strains representing both susceptible and resistant strains and 50 clinical isolates were tested. The standard medium did not support the growth of two control strains and three clinical isolates when the standardized inoculum was used in the disk diffusion test. The same medium with the addition of hemoglobin was introduced. This medium supported the growth of all strains. The correlations between the MICs and the zones of inhibition were calculated for penicillin, ampicillin, cefuroxime, erythromycin, tetracycline, doxycycline, ciprofloxacin, and spectinomycin. The range of MICs for the clinical isolates were broad, without bimodal distribution, for all antibiotics, except ciprofloxacin and spectinomycin. With the susceptibility distribution of MICs and zones near the current susceptible and intermediate or intermediate and resistant limits, a low reproducibility of tests and a high frequency of minor interpretive errors can be expected. A revision of MIC breakpoints seems warranted but can only be done after renewed clinical evaluation of different treatment regimens.

Ampicillin↗

Selective medium for isolation of Treponema hyodysenteriae.

Pure cultures of six pathogenic isolates of Treponema hyodysenteriae, the colonic mucosal scrapings of seven pigs with acute swine dysentery, and feces from seven unaffected pigs were diluted in phosphate-buffered saline and plated on Trypticase soy agar with 5% citrated bovine blood (TSA) and TSA with various levels of spectinomycin (TSA-S). The plates were incubated at 42 degrees C in a vented GasPak jar with a cold palladium catalyst and either 80:20 H2-CO2 by evacuation and refilling or a H2-CO2 generator envelope. Viable cell counts of the six pathogenic isolates were not altered by plating on TSA-S with 400 mug of spectinomycin per ml (TSA-S400) as compared with TSA alone. Dilutions of colonic mucosal scrapings from seven pigs with acute swine dysentery showed numbers of T. hyodysenteriae to be unchanged when plated on TSA-S400. Flora other than T. hyodysenteriae present in acute swine dysentery was inhibited, on the average, by 99.99%. Plating of dilutions of feces of unaffected pigs on TSA-S400 showed inhibition of flora that averaged more than 99.9%. Pathogenicity of T. hyodysenteriae was not altered by isolation or serial passage on TSA-S400.

Animals↗

Sectinomycin in the treatment of gonorrhoea in females and males.

126 female patients with proven gonococcal infection were treated with 4 g. spectinomycin bihydrochloride given intramuscularly in a single does. In 120 cases followed up there were four possible treatment failures, giving a cure rate of 97-6 per cent. 99 male patients with acute gonococcal urethritis were treated with a single dose of 2, g. sectinomycin bihydrochloride. Of 88 cases followed up, there were three possible treatment failures, giving a cure rate of 96-6 per cent. Spectinomycin is an important addition to gonorrhoea therapy but should be reserved for penicillin sensitive patients and penicillin insensitive infections.

Adolescent↗

Activity in vitro of ten antimicrobial agents against Neisseria gonorrhoeae. A study of the correlation between the sensitivities.

105 Belgian strains of Neisseria gonorrhoeae were tested for their sensitivity to penicillin, ampicillin, rifampicin, erythromycin, tetracycline, streptomycin, spectinomycin, sulphamethoxazole, trimethroprim, and a combination of sulphamethoxazole and trimethroprim in a 5:1 ratio. Distribution and median values of minimum inhibitory concentrations (MICs) are given and discussed. 42 per cent. of strains were relatively resistant to penicillin (MIC greater than or equal to 0-04 mug/ml.), but only 2 per cent. showed high-level resistance (MIC greater than or equal to 0-38 mug/ml.), which is comparable with the prevalence of decreased sensitivity found in other European countries. A significant positive correlation (P less than or equal to 0-01, rank correlation coefficient) is found between the sensitivities to penicillin, ampicillin, erythromycin, tetracycline, and streptomycin, except for the ampicillin-erythromycin and ampicillin-tetracycline pairs. Rifampicin is correlated with tetracycline. No correlation is found between the sensitivities to spectinomycin and any of the other drugs. The combination of sulphamethoxazole and trimethoprim in a 5:1 ratio also shows a significant positive correlation with penicillin and ampicillin and with sulphamethoxazole and trimethoprim separately.

Ampicillin↗

Treatment of pharyngeal gonorrhea due to beta-lactamase-producing gonococci.

Between March 1978 and October 1980 seven patients with beta-lactamase-producing gonococci in the pharynx were treated wit spectinomycin of cefuroxime or both. One-day treatment with spectinomycin was effective in only one of six patients and with cefuroxime in only one of four patients. Prolonged treatment with cefuroxime was successful in all five cases so treated.

Cefuroxime↗

Antibiotic sensitivity patterns of penicillinase-positive and penicillinase-negative strains of Neisseria gonorrhoeae isolated in Fukuoka, Japan.

Penicillinase production and minimum inhibitory concentrations (MICs) of penicillin G, amoxycillin, doxycycline, and spectinomycin were studied for 155 gonococcal strains isolated in Fukuoka, Japan, between April and December 1981. Of 155 isolates, 25 (16.1%) strains were identified as penicillinase-producing Neisseria gonorrhoeae (PPNG) by a rapid iodometric test. The antibiotic sensitivity of 130 penicillinase-negative (non-PPNG) and 25 PPNG strains was compared. The mean MIC of penicillin G for non-PPNG strains was 0.65 microgram/ml. Twenty-five PPNG strains had MICs of penicillin G between 6.25 and greater than 100 micrograms/ml. The susceptibility to amoxycillin and doxycycline of PPNG strains was significantly lower than that of non-PPNG strains. All the strains proved to be sensitive to spectinomycin. The MICs of four antibiotics for non-PPNG strains were significantly correlated.

Amoxicillin↗

Rosoxacin in the treatment of uncomplicated gonorrhoea in men.

Between 3 January and 4 March 1983 we treated 200 male patients diagnosed as having uncomplicated gonococcal urethritis with one of two regimens. They were divided into two groups and randomly assigned to treatment with either 2 g spectinomycin administered intramuscularly (group A) or 300 mg rosoxacin by mouth (group B). Of 187 isolates tested for the production of beta-lactamase, 101 (54%) were penicillinase producing Neisseria gonorrhoeae (PPNG) strains. All 81 cases followed in group A (spectinomycin) were cured, compared with 88.5% (77 out of 87) of the patients followed in group B (rosoxacin). We concluded that rosoxacin at a dosage of 300 mg administered orally was fairly effective in the treatment of gonococcal urethritis in men caused by both PPNG and non-PPNG strains.

4-Quinolones↗

Antimicrobial susceptibility of Neisseria gonorrhoeae isolated in Durban, South Africa.

One hundred and forty clinical isolates of Neisseria gonorrhoeae were screened for production of penicillinase by the intralactam strip method and chromogenic cephalosporin test. Minimum inhibitory concentrations (MICs) of penicillin, ampicillin, tetracycline, cefoxitin, cefuroxime, cefotaxime, sulphamethoxazole-trimethoprim (ratio 19/1), and spectinomycin, were measured for 100 strains by the agar dilution method. Seven (5%) of the 140 isolates were identified as penicillinase producing N gonorrhoeae (PPNG). The MICs of penicillin for the seven PPNG strains ranged from 0 X 25 mg/1 to 2 mg/1. Of the 93 non-PPNG strains, 80 (86%) were fully susceptible to penicillin with MICs ranging from 0 X 0037 mg/1 to 0 X 06 mg/1 and 13 (14%) were of intermediate penicillin resistance with MICs greater than or equal to 0 X 125 mg/1. Of the 100 isolates tested, 86% were fully susceptible to tetracycline with MICs of less than 1 mg/1. No spectinomycin resistant strains were encountered in this study. All gonococcal strains were susceptible to the cephalosporins tested as well as to sulphamethoxazole-trimethoprim.

Ampicillin↗

In vitro activity of selected antimicrobial agents against penicillinase producing Neisseria gonorrhoeae (PPNG) and non-PPNG strains.

One hundred and twelve penicillinase producing Neisseria gonorrhoeae (PPNG) isolates and the same number of non-PPNG isolates were obtained from patients attending the genitourinary department of this hospital. Susceptibilities to six beta lactam antibiotics--ceftriaxone, cefotaxime, cefuroxime, ceftazidime, amoxycillin, and temocillin--to the combined formulation of amoxycillin and clavulanic acid, Augmentin, and to the aminocyclitol, spectinomycin, were compared by assessing their minimum inhibitory concentrations (MICs). Results showed that all the cephalosporins used in this study had good in vitro activity against both PPNG and non-PPNG strains, and ceftriaxone had the lowest MICs. Temocillin and Augmentin also showed good activity against both types of strain. Spectinomycin resistance was shown in about 4% of the PPNG isolates but was not found in any non-PPNG strains.

Amoxicillin↗

Biotypes, serotypes, and susceptibility to antibiotics of 60 Haemophilus influenzae strains from genitourinary tracts.

Sixty strains of Haemophilus influenzae were isolated from the genitourinary tracts of adults: 19 from cervicovaginal secretions, one from a woman with bartholinitis, 37 from urethral exudates, and three from urine. Non-capsulated strains were recovered predominantly, and biotype III accounted for 28 isolates and biotype IV for 25. Many of the H influenzae strains were found to be resistant to one or more of the antibiotics commonly used against sexually transmitted diseases. Resistance to tetracycline was prevalent and was found in 17 of the strains. Ten strains were ampicillin resistant and beta lactamase producing. Kanamycin resistance was less common (two strains). Trospectomycin (U-63366), a new spectinomycin analogue, was eight to 16 times more active than spectinomycin. All the quinolones tested were very active against all strains and may provide an effective alternative for the treatment of resistant H influenzae in genitourinary infections.

Adult↗

Efficacy of a single dose of oral antibiotic given within two hours of birth in preventing watery mouth disease and illthrift in colostrum-deficient lambs.

An antibiotic with a product licence limited to the treatment and control of infectious bacterial enteritis associated with Escherichia coli in piglets was tested for its ability to control watery mouth disease in neonatal lambs. Three groups of lambs were kept in conditions commonly encountered in intensive lambing systems, where high levels of environmental bacterial contamination may be expected. They were allocated at birth to: a control group (group 1) consisting of 18 colostrum-deprived lambs; group 2, consisting of 17 lambs given one feed of colostrum when they were two hours old; and group 3, consisting of 18 colostrum-deprived lambs given spectinomycin orally when they were two hours old. Nine group 1 lambs became diseased and were killed for humane reasons. Blood biochemical changes included hyperglycaemia followed by hypoglycaemia, lactacidaemia, hypoproteinaemia and metabolic acidosis, and postmortem examination of the diseased lambs showed signs consistent with endotoxaemia and a clinical diagnosis of watery mouth disease. Coliforms were isolated from the blood of all group 1 lambs and from half the lambs in groups 2 and 3, but endotoxaemia and watery mouth disease occurred only in group 1 lambs. The results for groups 2 and 3 showed that neither colostrum nor antibiotic at the rates and frequency used prevented bacteraemia, although consecutive samples were positive only on three occasions. Group 3 lambs consistently grew more rapidly than the surviving group 1 lambs and as rapidly as group 2 lambs. There was no evidence that male lambs were more prone to watery mouth disease than female lambs. The results indicated that the antibiotic spectinomycin did not induce endotoxaemia during low-grade bacteraemia and that a single oral dose given within two hours of birth protected colostrum-deprived lambs delivered into a contaminated indoor environment against watery mouth disease.

Administration, Oral↗

Fragmentation of the ribosome to investigate RNA-ligand interactions.

RNA molecules perform a variety of important and diverse functions and, therefore, an understanding of their structure and interaction with proteins and ligands is essential. Large RNA molecules (for example, the ribosomal RNAs) are complex and hence reports describing their fragmentation into functional subdomains has provided a means for their detailed analysis. We present here an in vivo approach to study RNA-ligand interactions. This is based on the concept that an RNA fragment could mimic a drug-binding site present on the intact molecule. Overexpression of the fragment would sequester the drug thereby permitting the continued functioning of the ribosome and, thus, ensuring cell viability. Accordingly, a fragment of 16S rRNA encompassing the spectinomycin-binding domain in helix 34 (nucleotides 1046-1065 and 1191-1211) was cloned and in vivo expression resulted in drug resistance. Furthermore, an RNA fragment lacking flanking sequences to helix 34 was also selected from among a pool of random rRNA fragments and shown to confer spectinomycin resistance. A similar in vitro approach is also described for the analysis of rRNA molecules that interact with the yeast elongation factor 3 (EF-3).

Anti-Bacterial Agents↗

The activity of four antimicrobial agents. Including three nitroimidazole compounds, against Bacteroides sp.

Forty strains of Bacteroides sp. were tested against three nitroimidazole compounds, metronidazole, tinidazole and nimorazole and the aminoglycosidic antibiotic spectinomycin. The effect of altering the inoculum and the presence of serum upon the minimum inhibitory concentration (MIC) was also noted. The three nitroimidazole compounds were all very active (average MIC = circa 0.25 mg/l). Tinidazole was twofold more active. The MIC of spectinomycin was 32 mg/l.

Anti-Bacterial Agents↗

Antimicrobial susceptibility of non-penicillinase and penicillinase-producing Neisseria gonorrhoeae strains isolated in Tripoli, Libya.

Neisseria gonorrhoeae culture gave a positive result in 42 of 64 male adults with purulent urethral discharge. The majority of the infections were acquired outside Libya. Twenty-seven strains (64.3%) were non-penicillinase producing (NPPNG) and 15 (35.7%) were penicillinase producing (PPNG) by starch paper technique. Antimicrobial susceptibility of the strains to 5 antibiotics was carried out by agar-plate dilution technique. Twenty-three NPPNG strains (54.8%) were susceptible to penicillin with a minimum inhibitory concentration (MIC) of less than or equal to 0.5 micrograms/ml. In 4 strains (9.5%), a high resistance to penicillin (MIC greater than or equal to 16 micrograms/ml) appeared to be chromosomally-mediated (CMRNG). All PPNG strains were resistant to penicillin (MIC greater than or equal to 1 microgram/ml). While resistance to erythromycin (MIC greater than or equal to 1 microgram/ml) and tetracycline (MIC greater than or equal to 1 microgram/ml) was observed in 5 strains, resistance to kanamycin (MIC 32 micrograms/ml) and spectinomycin (MIC 64 micrograms/ml) was present in only one strain. Whereas no significant differences were recorded in MICs of erythromycin, tetracycline, kanamycin and spectinomycin between NPPNG and PPNG strains, one PPNG strain was found to be resistant in vitro to all 5 antibiotics.

Drug Resistance, Microbial↗

In vitro activity of temocillin against Neisseria gonorrhoeae including penicillinase-producing strains.

169 penicillinase-producing strains of Neisseria gonorrhoeae (PPNG) isolated in the United Kingdom were examined for susceptibility to temocillin and spectinomycin. A further 25 PPNG strains and 214 non-penicillinase-producing strains were examined against temocillin, spectinomycin, amoxycillin, cefuroxime and penicillin. Minimum inhibitory temocillin concentrations ranged from 0.36 to 5.0 mg/L with a mode at 1.25 mg/L. The distributions of sensitivities to other agents were in keeping with those previously described.

Amoxicillin↗

Efficacy of turkey herpesvirus vaccine when administered simultaneously with fowl pox vaccine.

The efficacy of the turkey herpesvirus (HVT) vaccine in protecting chickens challenged with virulent Marek's disease (MD) virus was unaffected by the presence of either the chick embryo fowl pox vaccine or fowl pox vaccine derived from cell culture. Conversely the HVT vaccine did not affect the efficacy of the fowl pox vaccine in chickens challenged with pathogenic fowl pox virus. A combination of spectinomycin dihydrochloride pentahydrate and lincomycin hydrochloride monohydrate as well as spectinomycin sulfate tetrahydrate were found to be compatible with the HVT and fowl pox vaccines as demonstrated by resistance after challenge with virulent MD virus or fowl pox virus.

Animals↗