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Biomedical subjects

S A Lerner

Publications and source records attributed to S A Lerner.

At least 73 records · Page 4Linked to original sources
PubMed1982

Susceptibility of Neisseria meningitidis and Neisseria gonorrhoeae isolates to N-formimidoyl thienamycin.

A diverse collection of 123 meningococcal and 126 gonococcal isolates was tested for susceptibility to N-formimidoyl thienamycin (N-F-thienamycin; MK0787) and to penicillin G (PEN). All of the meningococci were susceptible to both of these, as well as to rifampin. Among gonococci, beta-lactamase-producing strains, which were resistant to PEN, were susceptible to N-F-thienamycin. Among non-beta-lactamase-producing strains, the minimal inhibitory concentrations of N-F-thienamycin and PEN were less than or equal to 1.28 micrograms/ml. Of these, the strains with PEN minimal inhibitory concentrations toward the higher end of the range were likely to be more susceptible to N-F-thienamycin, whereas the strains that were highly susceptible to PEN were likely to have higher minimal inhibitory concentrations of N-F-thienamycin.

Anti-Bacterial Agents↗
PubMed1982

Disseminated blastomycosis in a pregnant woman: review of amphotericin B usage during pregnancy.

Disseminated blastomycosis was diagnosed in a 27-yr-old woman during her twenty-eighth week of pregnancy. Her skin lesions resolved promptly on treatment with amphotericin B. At full-term delivery when the mother had already received 1,536 mg of amphotericin B, the infant was normal and the placenta showed no evidence of blastomycotic infection. After administration of 16 mg of amphotericin B over 140 min, at delivery the concentrations of amphotericin B in serum of blood samples from the mother and the cord were 0.32 and 0.12 micrograms/ml, respectively. The published experience with systemic mycoses and amphotericin B treatment in pregnant women is reviewed. There is no evidence of teratogenesis or persistent toxic side effects in infants delivered from mothers treated with this drug during pregnancy.

Adult↗
PubMed1981

Localization of an amikacin 3'-phosphotransferase in Escherichia coli.

A plasmid-encoded enzyme reported by us to phosphorylate amikacin in a laboratory strain of Escherichia coli has been localized in the bacterial cell. More than 88% of this amikacin phosphotransferase (APH) activity was retained in spheroplasts formed by ethylenediaminetetraacetate-lysozyme treatment of an APH-containing E. coli transconguant known to form spheroplasts readily. By comparison, the spheroplasts retained 94% of deoxyribonucleic acid polymerase I and 98% of glutamyl-transfer ribonucleic acid synthetase, two internal markers, whereas less than 10% of the activity of a periplasmic marker, acid phosphatase, was present in spheroplasts. Treatment of whole cells of the transconjugant with chemical probes incapable of crossing the plasma membrane obliterated acid phosphatase activity, whereas the internal markers deoxyribonucleic acid polymerase I, glutamyl-transfer ribonucleic acid synthetase, and beta-galactosidase were virtually unaffected after treatment for 5 min; more than 60% of the APH activity remained. As a control, similar chemical treatment of sonic extracts, in which enzymes were not protected by bacterial compartmentalization, produced more extensive reduction in the activities of all test enzymes, including APH. Spheroplasts preincubated with adenosine triphosphatase were shown by thin-layer chromatography to phosphorylate amikacin. Spheroplasts of cells grown in the presence of H(3) (32)PO(4) were shown to utilize internally generated adenosine 5'-triphosphate in the phosphorylation of amikacin. The absence of (32)P-phosphorylated amikacin after incubation of [gamma-(32)P]adenosine 5'-triphosphate with spheroplasts confirmed that exogenous adenosine 5'-triphosphate was not used in the reaction. These results suggest an internal location for APH. This conclusion has implications for the role of such enzymes in aminoglycoside resistance of gram-negative bacteria.

Adenosine Triphosphatases↗
PubMed1980

Prevalence and site-pathogen studies of Neisseria meningitidis and N gonorrhoeae in homosexual men.

Prevalence and site-pathogen studies of pathogenic Neisseria were conducted in 815 homosexual men over a 12-month period. Neisseria meningitidis was isolated from more patients than N gonorrhoeae (43.1% vs 33.1%). A high oropharyngeal carriage of n meningitidis (42.5%) was present, with much lower urethral (0.7%) and rectal (2.0%) colonization. Although N meningitidis urethral isolates were associated with urethral discharge in five of six patients, N meningitidis in the oropharynx or rectum was not usually associated with clinical illness. Neisseria meningitidis was usually isolated from only one site in individual patients. Neisseria gonorrhoeae was isolated from the urethra (18.5%), rectum (16.3%), and oropharynx (5.6%). Of the 270 patients with gonococcal infection, 49.1% had urethral gonorrhea only, and 20.7% were infected at two or more body sites. Virtually all patients with urethral infection had symptoms of urethritis, whereas 89.1% of patients with oropharyngeal infection and 61.9% of patients with anorectal infection had no local symptoms.

Anal Canal↗
PubMed1980

Aminoglycoside ototoxicity.

Aminoglycoside antibiotics are frequently employed in the treatment of serious infections caused by aerobic gram negative bacilli. The use of these potent antibacterial agents is limited by the risks of ototoxicity and nephrotoxicity. Aminoglycosides are excreted by glomerular filtration at a rate proportional to the serum concentration. Impaired renal excretion reduces the rate of clearance from the serum. Utilizing information about aminoglycoside pharmacokinetics, the susceptibility of infecting pathogens to aminoglycosides, and risk factors for ototoxicity, physicians can attempt to optimize the administratioin of an aminoglycoside to maximize the therapeutic efficacy and to minimize the risk of ototoxicity. Periodic assessments of renal function and of aminoglycoside levels in the serum are essential to guide therapy. The otolaryngologist and audiologist must be able to provide information about ototoxicity to medical colleagues using these drugs. They should also be prepared to evaluate and follow patients who develop sensorineural inner ear dysfunction during or after a course of therapy with an aminoglycoside antibiotic.

Adult↗
PubMed1979

Clinical isolation and characterization of aminoglycoside-resistant small colony variants of Enterobacter aerogenes.

Small colony variants of Enterobacter aerogenes, as well as the parental large colony type, grew in blood drawn for cultures on three separate days from a patient who had received suboptimal gentamicin therapy. Minimum inhibitory concentrations of four aminoglycoside antibiotics were eight to more than 16 times higher for small colony variants than for the normal large colony type. Small colony variants had defective catalase activity, which may have interfered with oxidative metabolism and aminoglycoside uptake. Small colony variants reverted readily to the parental type in vitro in the absence of aminoglycosides. Clinically isolated small colony variants appeared similar to those selected in the presence of gentamicin in vitro, with respect to colony morphology, aminoglycoside resistance and catalase deficiency. The isolation of small colony variants during gentamicin therapy in vivo suggests that such variants may be a cause of treatment failure in patients receiving aminoglycosides.

Aminoglycosides↗
PubMed1979

Effect of clavulanic acid on the in vitro synergism between carbenicillin and gentamicin against Serratia marcescens.

Clavulanic acid, a potent beta-lactamase inhibitor, reduced the minimum inhibitory concentrations of carbenicillin for 13 of 15 clinical isolates of Serratia marcescens by at least eightfold. The combination of clavulanic acid and carbenicillin also exhibited synergistic activity with gentamicin against 11 of 15 isolates tested, including 9 of 10 strains which were highly resistant to carbenicillin (minimum inhibitory concentration >/= 8,000 mug/ml) and had previously been found resistant to the synergistic activity between carbenicillin and gentamicin.

Anti-Bacterial Agents↗
PubMed1979

Amikacin resistance associated with a plasmid-borne aminoglycoside phosphotransferase in Escherichia coli.

Enzymatic phosphorylation of amikacin has not been reported previously in gram-negative bacteria. We found that extracts of MP1, a mutant of Escherichia coli JR66/W677 that is resistant to amikacin, were able to phosphorylate this aminoglycoside more rapidly than were extracts of the parental strain. Conjugal transfer of resistance from MP1 to a recipient strain was accompanied by acquisition in the transconjugants of amikacin phosphotransferase activity and of a 57-megadalton plasmid present in the donor. Partial purification of the phosphotransferase activity on amikacin-Sepharose 4B yielded an enzyme with a substrate spectrum similar to that of the 3'-neomycin-kanamycin phosphotransferase II found E. coli, except that it was also active against amikacin. A mutant of MP1, MP5, had increased susceptibility to amikacin and reduced phosphotransferase activity. MP9, a mutant MP5, was more resistant to amikacin and had increased phosphotransferase activity. The mutations leading to these alterations of amikacin susceptibility and amikacin phosphotransferase activity were transferable with the same plasmid that was associated with amikacin resistance and phosphotransferase activity in MP1. These studies demonstrate that resistance to amikacin in a laboratory strain of E. coli is due to an aminoglycoside phosphotransferase coded by a transferable plasmid-borne gene.

Amikacin↗
PubMed1978

Simplified radioenzymatic assay for chloramphenicol.

A simplified radioenzymatic assay for chloramphenicol was developed by eliminating the need for cumbersome extraction procedures. After the acetylation of chloramphenicol with [(14)C]acetyl coenzyme A in the presence of chloramphenicol acetyltransferase, the reaction mixture was added to a toluene-based scintillation fluid. Since (14)C-acetylated chloramphenicol is more soluble than [(14)C]acetyl coenzyme A in toluene, the radioactive product could be counted directly. The rapidity of this assay, as well as its accuracy, precision, and specificity, makes it particularly suitable for clinical use. In contrast to previous reports of enzymatic assays for chloramphenicol, we have found that results of the assay of standards prepared in serum were up to 25% higher than those of standards prepared in saline, cerebrospinal fluid, or urine.

Acetyl Coenzyme A↗
PubMed1978

Effects of radiopharmaceuticals on radioenzymatic assays of aminoglycoside antibiotics: interference by gallium-67 and its elimination.

Radionuclides currently used in clinical medicine were evaluated for their possible interference with radioenzymatic assays of aminoglycoside antibiotics. Of the radiopharmaceuticals tested, only (67)Ga citrate interfered with the radioenzymatic assay of gentamicin. Radioenzymatic assay of serum samples obtained from patients receiving (67)Ga yielded gentamicin concentrations falsely elevated by more than 1 mug/ml for approximately 1 week after (67)Ga administration. A procedure was developed to eliminate (67)Ga interference with radioenzymatic assays of aminoglycoside antibiotics. After (67)Ga citrate was spotted onto phosphocellulose filter disks, the filters were immersed in 7.2 N HCl, and radioactivity was removed by successive extractions of the acid phase with diisopropyl ether. After three extractions, less than 0.1% of the original radioactivity remained. Similar extraction of disks containing (14)C-adenylylated gentamicin or tobramycin or (14)C-acetylated amikacin had no effect on (14)C radioactivity. The concentrations of aminoglycosides in serum standards supplemented with (67)Ga citrate were determined accurately by radioenzymatic assays followed by extraction with diisopropyl ether. Concentrations of gentamicin in six serum samples from patients injected with (67)Ga during gentamicin therapy, as determined by radioenzymatic assay and extraction, were within 9% of the results obtained by reassay of the same samples after the decay of (67)Ga.

Aminoglycosides↗
PubMed1977

Comparative clinical studies of ototoxicity and nephrotoxicity of amikacin and gentamicin.

A comparative study of the oto- and nephrotoxicity of amikacin and gentamicin was carried out prospectively. Twenty-six gentamicin-treated patients and 27 amikacin-treated patients were monitored for changes in auditory and renal function during and after therapy. Thirteen of those treated with gentamicin and 20 of those treated with amikacin underwent vestibular caloric testing which could be evaluated for evidence of toxicity. In four (15.4%) of the gentamicin-treated patients, nephrotoxicity developed; no such toxicity was seen in the amikacin-treated patients. This difference may have been due to a fortuitously higher incidence of pretreatment renal impairment in the gentamicin-treated group. In two gentamicin-treated patients (7.7%), ototoxicity developed (one auditory, one vestibular), and in two amikacin-treated patients (7.4%), auditory toxicity developed. Statistical analysis of oto- and nephrotoxicity and their risk factors was not attempted because of the small numbers of patients who could be evaluated. Additional patients are being studied.

Adult↗
PubMed1977

Cutaneous abscesses. Anaerobic and aerobic bacteriology and outpatient management.

Specimens from 135 cutaneous abscesses in outpatients were cultured anaerobically and aerobically. Of these, 4% were sterile and 29% yielded pure cultures, predominantly of Staphylococcus aureus. Aerobic species were isolated from all anatomic areas. Anaerobes were found with a frequency comparable to aerobes in all nonperineal areas except the hand. In contrast, abscesses in the perineal region contained a greater variety and frequency of anaerobes. Only two patients were febrile. All abscesses were treated with incision and drainage, and all healed without complication, including those 74% that were treated without adjunctive antibiotics. Primary management of cutaneous abscesses should be incision and drainage. In general, routine culture and antibiotic therapy are not indicated for localized abscesses in patients with presumably normal host defenses.

Abscess↗
PubMed1977

Aspergillus terreus osteomyelitis.

Aspergillus terreus infection limited to the L1-2 disk space and first and second lumbar vertebrae developed in a patient not predisposed to invasive aspergillosis. The observation of morphologically distinct secondary spores (aleuriospores) on microscopic examination of open biopsy specimens permitted a preliminary identification of A terreus, which was confirmed by culture. The infection was eradicated with amphotericin B in a total dose of 3 gm. Aspergillus terreus is usually a saprophyte. The present case and four others collected from the literature establish this species as an invasive pathogen.

Adult↗
PubMed1976

In vitro activity of gentamicin, amikacin and netilmicin alone and in combination with carbenicillin against Serratia marcescens.

The inhibitory and bactericidal effects of gentamicin, amikacin, netilmicin (Sch 20569), and carbenicillin were tested against 55 clinical isolates of Serratia marcescens that had been subtyped into 26 strains by biotyping and serotyping. Three major patterns of resistance to gentamicin, netilmicin, and carbenicillin were recognized among these isolates. (i) Most of the 27 isolates that were susceptible to gentamicin (minimal bactericidal concentration [MBC] </=6.25 mug/ml) were susceptible to carbenicillin (MBC </=125 mug/ml) and resistant to netilmicin (MBC >/=12.5 mug/ml). (ii) Most of the 11 isolates with moderate resistance to gentamicin (MBC of 12.5 to 25 mug/ml) were also susceptible to carbenicillin and resistant to netilmicin. (iii) The 17 isolates with high-level resistance to gentamicin (MBC >/= 50 mug/ml) were all highly resistant to carbenicillin (MBC >/=8,000 mug/ml) but susceptible to netilmicin (MBC </=6.25 mug/ml). The susceptibility to amikacin was unpredictable among these groups of isolates but, overall, 80% of the isolates were killed by 25 mug of amikacin/ml, which is within the range of peak serum concentrations used therapeutically. Clinically attainable subinhibitory concentrations of carbenicillin enhanced the activity of the three aminoglycosides against all isolates with MBCs of carbenicillin </=2,000 mug/ml. The 17 isolates with high-level resistance to carbenicillin and gentamicin, as well as the four isolates with high-level resistance to carbenicillin but not to gentamicin, were not susceptible to such enhancement of aminoglycoside activity by carbenicillin.

Amikacin↗
PubMed1976

Characteristics of atypical Neisseria gonorrhoeae from disseminated and localized infections.

Approximately 6% of 1,200 clinical isolates of Neisseria gonorrhoeae were atypical because they produced smaller than normal colonies on conventioal chocolate agar and fermented glucose weakly. Auxotyping studies indicated that these atypical strains required for growth arginine, uracil, and, in most instances, hypoxanthine. In addition, all of them were susceptible to 0.02 U of penicillin/ml. None of the normal colony isolates, including those susceptible to the same low concentration of penicillin, had the same nutritional characteristics. Atypical strains comprised almost half of the isolates from disseminated infections, but only 5% of those from localized infections. Auxotyping was used to identify the contact of a patient who became reinfected nine times with an atypical gonoccal strain. In addition to its usefulness in such epidemiological studies, this technique has enabled us to distinguish a subgroup of gonococci with apparent increased pathogenicity.

Culture Media↗