Localized cutaneous reaction to intravenous pentamidine.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
B Suh
Publications and source records attributed to B Suh.
Development of new antibiotic resistance in methicillin-resistant but not methicillin-susceptible Staphylococcus aureus.
The frequency of infections caused by multidrug-resistant Staphylococcus aureus continues to increase while the numbers of alternative therapeutic agents remain limited. To investigate the changing patterns of in-vitro susceptibility of S. aureus to 16 antibiotics, 190 clinical isolates from two different years were studied. The MICs of methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) strains isolated in 1987 were compared with those of similar numbers of strains isolated in 1989. For MRSA > or = 90% of isolates from both years were resistant to clindamycin, gentamicin and erythromycin. These strains remained highly susceptible to vancomycin (100%), minocycline (90%) and rifampicin (100%). The greatest increase in resistance was observed for ofloxacin (2% in 1987 vs 62% in 1989); cross-resistance to all of the quinolones tested was demonstrated. MSSA strains remained susceptible to vancomycin (100%), minocycline (98%), rifampicin (100%), clindamycin (90%), gentamicin (90%) and ciprofloxacin (98%). It is concluded that methicillin susceptibility is a useful marker for selecting potential agents for the treatment of infections caused by S. aureus. A combination of minocycline and rifampicin may be a useful alternative to vancomycin for treating MRSA infections.
Drug Resistance, Microbial↗
Conservative management of cervical pregnancy with subsequent fertility.
The reported incidence of cervical pregnancies with subsequent fertility is extremely low. We report a case managed conservatively that allowed for future fertility, and ultimately the delivery of a viable infant at term. The conservative management and a review of the literature are discussed.
Adult↗
New rapid assay for nafcillin in serum by spectrofluorometry.
A new, rapid method for measuring serum levels of nafcillin by spectrofluorometry is described. The method involves extraction of 2 ml of acidified serum with n-butyl chloride, subjecting the organic solvent layer to excitation at 340 nm, and measuring the relative intensity of emission fluorescence at 380 nm. An excellent linear correlation exists between serum levels of nafcillin and the relative intensity in a drug concentration range of 0.25 to 150 mug/ml. The results obtained by this spectrofluorometric technique are in complete accord with those obtained by the conventional microbiological assay using Staphylococcus aureus ATCC 6538P. The method is not interfered with by elevated levels of endogenous metabolic products or the presence of other drugs, including a number of antimicrobial agents. The assay is interfered with, however, by the presence of salicylates, for which appropriate correction can easily be made. A salicylate assay employing a spectrofluorometric technique is also described.
Biological Assay↗
Oral neomycin dosage schedules for suppression of ammonia production by bowel flora.
To better define a minimal but optimal dose of oral neomycin to suppress ammonia production by bowel flora, several dosage regimens were examined in normal healthy volunteers. Fecal urease activity was quantitatively determined and was used as an indirect measure of intrinsic ammonia production by bowel flora. Large doses of neomycin were found to exert inhibition of fecal urease for many days. There was considerable variation in enzymatic activity among subjects even after adjustments were made for protein content of the stool. Depending on the dose, there was a 1- to 3-day lag in neomycin effect on stool urease activity and several days of continued effect. The most effective regimen of those studied was a loading dose of 6 g of neomycin given in three divided doses on day 1, followed by 1 g twice daily.
Adult↗
Rapid assay for determination of trimethoprim and sulfamethoxazole levels in serum by spectrofluorometry.
A rapid spectrofluorometric method for determining the levels of both trimethoprim and sulfamethoxazole from the same specimen of serum is described. The method involves stepwise extraction of the specimen first with chloroform at an alkaline pH (pH 9.0) for trimethoprim followed by n-butyl chloride at an acidic pH (pH 2.0) for sulfamethoxazole. To quantitate trimethoprim, the chloroform layer was subjected to fluorometry by exciting the specimen at 295 nm and measuring the relative intensity at 330 nm. To determine sulfamethoxazole levels, the n-butyl chloride layer was subjected to fluorometry by exciting the specimen at 285 nm and measuring the relative intensity at 330 nm. Relative intensities were linear (r greater than 0.99) over the concentration ranges of 0.5 to 40 microgram/ml for trimethoprim and 1 to 400 microgram/ml for sulfamethoxazole. Values obtained by this spectrofluorometric procedure were in excellent agreement with those obtained by a conventional fluorometric assay for trimethoprim and a colorimetric assay for sulfamethoxazole. Elevated levels of endogenous metabolic products and numerous other drugs, including a number of antimicrobial agents, did not interfere with the method. Although salicylates interfere with the determination of sulfamethoxazole, an appropriate correction can be made. This method can also be used to determine the drug levels in cerebrospinal fluid.
Humans↗
Changes in protein binding during disease.
Disease states can alter protein binding of antimicrobials by either a reduction in the concentration of serum proteins or the accumulation of endogenous compounds, such as bilirubin and free fatty acids (FFA), that affect drug-protein interactions. In terms of protein concentration, extremely low levels of albumin (less than 2.5 m/100 ml) are required to markedly reduce binding of antimicrobials. In vitro addition of high concentrations of bilirubin and FFA to normal serum reduces binding of most antimicrobials. However, binding of some antibiotics appears to be enhanced at lower concentrations of FFA probably by an allosteric mechanism. These in vitro observations have been confirmed in sera from patients during heparin administration and patients with hyperbilirubinemia. Reduced protein binding of acidic antimicrobials in uremia appears to be associated with the accumulation of another, as yet unknown, endogenous binding inhibitor. Significant reduction in protein binding can affect the distribution of drugs and results of microbiologic assays.
Anti-Bacterial Agents↗
Theory and practical impact of binding of antimicrobials to serum proteins and tissue.
Binding of antimicrobials to serum proteins and tissue affects their distribution, elimination and antimicrobial activity. Penetration of drugs into most tissues and interstitial and inflammatory fluids correlates with level of free drug in serum. Serum protein binding can increase or decrease the rate of drug elimination depending on whether total or free drug is available to the excretory or metabolic routes of elimination. Binding to soluble intracellular proteins (ligandin and fatty acid binding protein) appears to be important in the cellular transport and elimination of antimicrobials by renal tubular secretion and hepatic extraction. Although only free, unbound drug is antimicrobially active, the lack of well designed studies has prevented precise quantitation of the influence of binding on therapeutic efficacy in vivo. Pharmacokinetic considerations predict that serum binding greater than 80% would be necessary to significantly reduce free levels of drug in the body. However, extensive protein binding is often compensated for by greater intrinsic activity of lipophilic antimicrobials.
Animals↗