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V Lorian

Publications and source records attributed to V Lorian.

At least 37 records · Page 2Linked to original sources

Predictive value of susceptibility tests for the outcome of antibacterial therapy.

A total of 510 charts of patients who received antibacterial agents were examined for clinical outcome and microbiology findings. A total of 382 patients (75%) had one or more specimens submitted for culture and susceptibility tests before the administration of the drugs; 298 (78%) of these had positive cultures and susceptibility tests were done. A total of 18 species were isolated. Of the 298 patients with organisms of known susceptibilities, 271 (91%) received antibacterial agents to which the respective organisms were susceptible and 219 of these patients (81%) improved (P less than 0.05). This high rate of good infectious diseases practice is probably due to two factors: (1) susceptibility tests results were available in most cases the next day after the submission of a specimen; (2) the medical board distributed guidelines for the use of antibiotics and monitored the compliance closely. The patients treated with antibacterial agents to which the bacteria were resistant improved in 3% and did not improve in 82% (P less than 0.05) of the patients. This study shows that choosing an antibacterial agent in accordance to the susceptibility test resulted in a high rate of improvement. When the choice of agent disregarded bacterial resistance in vitro, therapy almost always ended in failure. Therefore, susceptibility tests in vitro have a good predictive value for the outcome of antibacterial therapy.

Anti-Bacterial Agents↗

The post-antibiotic effect defined by bacterial morphology.

Three strains of Escherichia coli were incubated with either ciprofloxacin or ampicillin. Filamentation of bacteria was observed after 1-2 h. After 5 h of contact with either drug the percentage of filaments exceeded 90%. The organisms were washed and incubated on drug free medium. Antibiotics when bound to an enzyme render that enzyme inactive; upon removal of the organisms from the antibiotic, the synthesis of enzymes resumes. The period of time encompassing the inactive enzymatic state of the organism at the time of removal from the drug to the time that enzymes restore complete function is our definition of the post-antibiotic effect (pae). Bacterial morphology reflects the variations in activity of these enzymes. The pae was determined by both the morphology of the organisms and the current growth kinetic method. The presence of 10% filaments and 90% bacilli was selected to indicate the endpoint of the pae by morphological criteria. The pae by morphology was 4 h for ciprofloxacin and 3 h for ampicillin. By the growth kinetics method it was 2 h for ciprofloxacin and zero for ampicillin.

Ampicillin↗

Activity of amikacin and ampicillin in succession and in combination.

One strain each of Escherichia coli and Streptococcus faecalis were exposed to amikacin and ampicillin in combination as well as in succession. Exposure to ampicillin for 1 hr followed by amikacin for 3 or 4 hr had the greatest antibacterial activity when the antibiotics were applied in succession. The least effective exposures for both organisms were 1 hr to amikacin followed by 3 or 4 hr to ampicillin. Exposure to the antibiotics in combination each at 1 MIC had the overall greatest antibacterial activity. Simultaneous exposure to the antibiotic combination does not necessarily mean simultaneous activity of both ampicillin and amikacin on the E. coli. The cell wall autolytic activities produced by ampicillin are triggered within 10 min after physical contact with the bacteria. In contrast, amikacin requires at least 30 min after physical contact to manifest its activity on the ribosome. Although physical exposure to both antibiotics in the combination is simultaneous, the specific activity of each is in fact sequential, with ampicillin acting first. This explains the synergistic effect of the combination. It appears, therefore, that the synergistic or antagonistic affect of a drug combination is determined by the sequence and timing of the antibacterial manifestations of its components.

Amikacin↗

Effects of antibiotics on bacterial structure and their pathogenicity.

Subinhibitory concentrations of beta-lactam antibiotics as well as some other antibacterial agents alter the ultrastructure of bacteria. The separation of replicated genomes of Gram positive cocci is inhibited, and results in clusters of as many as 30 organisms held together by thick cross walls. The separation of the replicated genomes of Gram negative bacilli is also inhibited and results in the formation filaments. These altered forms of bacteria usually exhibit lower pathogenicity than their respective normal counterparts such as; decreased adherence to epithelial cells, higher susceptibility to phagocytosis and decreased output of bacterial enzymes. Contrary to common belief, subinhibitory concentrations do not generate a significant increase in bacterial resistance to the respective drug.

Animals↗

Amikacin-induced alterations in the structure of gram-negative bacilli.

Exposure of some species of Enterobacteriaceae and of Pseudomonas aeruginosa to amikacin results in structural alterations which coincide with a decrease in the number of colony forming units. Escherichia coli when exposed to amikacin at a concentration twice the minimum inhibitory concentration for 2 hr shows a reduction in the number of ribosomes in the center of the cell and an aggregation of nuclear material in a peculiar concentric pattern we called "tornado image." After 2-4 hr of exposure to amikacin at concentrations of two to five times the minimal inhibitory concentration, all species tested showed in addition to alterations in the distribution of ribosomes, ruptures in the cytoplasmic membrane, damaged cell walls, and in some instances complete loss of cellular shape. It appears that amikacin produces a lytic death of bacteria.

Amikacin↗

Ciprofloxacin in the treatment of pneumonia.

The use of ciprofloxacin as the sole agent in the treatment of 25 patients with pneumonias caused by susceptible organisms resulted in rapid cure. No side effects, superinfections, or recurrences were observed.

Adult↗

Penicillin-binding site on the Escherichia coli cell envelope.

The binding of 35S-labeled penicillin to distinct penicillin-binding proteins (PBPs) of the "cell envelope" obtained from the sonication of Escherichia coli was studied at different pHs ranging from 4 to 11. At low pH, PBPs 1b, 1c, 2, and 3 demonstrated the greatest amount of binding. At high pH, these PBPs bound the least amount of penicillin. PBPs 1a and 5/6 exhibited the greatest amount of binding at pH 10 and the least amount at pH 4. With the exception of PBP 5/6, the effect of pH on the binding of penicillin was direct. Experiments distinguishing the effect of pH on penicillin binding by PBP 5/6 from its effect on beta-lactamase activity indicated that although substantial binding occurred at the lowest pH, the amount of binding increased with pH, reaching a maximum at pH 10. Based on earlier studies, it is proposed that the binding at high pH involves the formation of a covalent bond between the C-7 of penicillin and free epsilon amino groups of the PBPs. At pHs ranging from 4 to 8, position 1 of penicillin, occupied by sulfur, is considered to be the site that establishes a covalent bond with the sulfhydryl groups of PBP 5. The use of specific blockers of free epsilon amino groups or sulfhydryl groups indicated that wherever the presence of each had little or no effect on the binding of penicillin by PBP 5, the presence of both completely prevented binding. The specific blocker of the hydroxyl group of serine did not affect the binding of penicillin. These observations suggest that a molecule of penicillin forms simultaneous bonds between its S at position 1 and sulfhydryl groups of PBP 5 and between its C-7 and free epsilon amino groups of PBP 5.

Bacterial Proteins↗

Salmonella susceptibility patterns in hospitals from 1975 through 1984.

The susceptibility of salmonella to commonly used antibiotics was analyzed for the 10-year period 1975 through 1984. The susceptibilities of 19,200 strains isolated from a yearly average of 211 hospitals nationwide and 1,508 strains isolated at the Kings County Medical Center in Brooklyn, N.Y., were described. Nationally, the susceptibility to nine antibacterial agents, including tetracycline, did not change markedly for the decade. The slight increase in susceptibility to tetracycline observed nationally may reflect the decreased clinical use of this antibiotic during the decade studied.

Drug Resistance, Microbial↗

Penicillin-binding proteins of filaments of Escherichia coli induced by low concentrations of nalidixic acid, oxolinic acid, novobiocin or nitrofurantoin.

Nalidixic acid, novobiocin, oxolinic acid and nitrofurantoin, each at low concentrations, cause filamentation of Gram-negative bacilli. Filamentation induced by beta-lactam antibiotics has been correlated to the binding of these antibiotics to specific penicillin-binding proteins (PBPs) of the envelope of Gram-negative bacilli. The studies reported herein indicate that the former group of non-beta-lactam antibiotics do not bind to any of the PBPs of Escherichia coli. However, PBP 1a, PBP 4 and PBP 5/6 of the filaments induced by these agents are increased significantly.

Acyltransferases↗

Staphylococci, in vitro and in vivo.

Strains of Staphylococcus aureus were grown in broth and by the membrane technique; both drug-free media and media containing cloxacillin were used. The staphylococci grown in broth containing cloxacillin showed one thick cross wall and were larger than those grown in drug-free broth: 1.6 micron in diameter as opposed to 0.9 micron. The staphylococci grown on membranes placed on agar containing cloxacillin were 2-3 microns in diameter and contained three or more cross walls. Mice were infected intraperitoneally with staphylococci. After treatment with cloxacillin, the peritoneal fluid and spleens contained staphylococci that were 2-3 microns in diameter with three or more cross walls. A staphylococcal endocarditis was induced in rabbits that were then treated with cloxacillin. The staphylococci in the vegetation of the treated rabbits were 2-3 microns in diameter and contained multiple cross walls. Large staphylococci with multiple cross walls were observed in specimens from patients with respiratory infections treated with beta-lactam antibiotics. It appears, therefore, that the ultrastructure of staphylococci in vivo is comparable to that of staphylococci grown on a solid support medium such as a membrane, and different from that of staphylococci grown in a liquid medium.

Animals↗

Low concentrations of antibiotics.

Low concentrations of antibiotics have been shown to alter the morphology and ultrastructure of bacteria. Exposure to beta-lactam antibiotics produces large Gram-positive cocci or long filaments of Gram-negative bacilli. The ultrastructure of staphylococci in infected animals and patients treated with beta-lactam antibiotics is comparable to the structure of staphylococci grown on a solid support medium such as hard agar or a filter membrane but is different from the structure of staphylococci grown in liquid media. Antibiotic-modified bacteria are phagocytosed very efficiently; considering their bacterial mass, Escherichia coli filaments are killed much more efficiently by PMNs than is an equal mass of normal sized bacilli. Antibiotics at sub-MIC alter the synthesis and excretion of bacterial metabolites which results in a change in their virulence. Antibiotics at a very low dosage, 10 mg of ampicillin per day which resulted in sub-MICs in the urine, were shown to cure urinary infections in patients. These therapeutic results were attributed to the inhibition of bacterial adherence by sub-MICs of ampicillin.

Animals↗