The erm gene product confers clindamycin resistance on Staphylococcus aureus. We report a clindamycin clinical failure where resistance developed on therapy in a D-test-positive strain. D tests of 91 clindamycin-susceptible, erythromycin-resistant S. aureus isolates showed that 68% of methicillin-susceptible and 12.3% of methicillin-resistant S. aureus strains were D-test positive.

Fluoroquinolones represent a major advance in antimicrobial chemotherapy. Currently, there are five fluoroquinolones approved by the FDA, and many more quinolones are expected to become available in years to come. Although their clinical utility is constantly expanding, they have been best studied in complicated urinary tract infections, chronic osteomyelitis caused by gram-negative bacilli, bacterial gastrointestinal infections such as traveler's diarrhea and typhoid fever, and uncomplicated gonococcal infections and in the prophylaxis of bacterial infections in patients with neutropenia. These agents have the convenience of oral administration, favorable pharmacokinetic properties, and low toxicity profiles but should be used advisedly because indiscriminate use may result in the early emergence of resistance.

The first report of prosthetic valve endocarditis due to a nutritionally variant streptococcus is presented. A 21-year-old woman developed persistent fever within one week of mitral valve replacement. Prosthetic valve dysfunction developed necessitating valve replacement. Cultures of blood and the excised prosthetic valve using routine media were negative; Streptococcus mitior grew as satellite colonies around Staphylococcus aureus and in beef heart infusion broth supplemented with 0.001% pyridoxine HCI, Treatment with penicillin G and streptomycin for six weeks was curative. Nutritionally variant streptococci should be considered in patients with prosthetic valve endocarditis and negative routine cultures.

An organic compound that inhibits drug binding in uremia has been isolated from the sera of chronic renal failure patients, and its chemical structure has been determined. Addition of the compound to normal human sera in vitro resulted in drug binding defects similar to those seen in uremia. The purification of this substance was accomplished by n-butyl chloride extraction of acidified (pH 3.0) uremic sera followed by column chromatography, thin-layer chromatography, and paper electrophoresis. From analytical studies including ultraviolet and fluorescence spectroscopy, gas chromatography, chemical ionization and electron impact mass spectrometry, and proton nuclear magnetic resonance spectroscopy, the chemical structure of the uremic binding inhibitor was deduced to be 2-hydroxybenzoylglycine. This confirms the hypothesis that the drug binding defect in uremia is due to the accumulation of endogenous metabolic products rather than an intrinsic structural defect in albumin.

A 40-yr-old man with chronic olecranon bursitis caused by Mycobacterium gordonae, a rare cause of human infection, was treated with antimicrobial therapy with an excellent response. Successful treatment for reported cases of synovial and bursal infection caused by atypical mycobacteria has usually involved a combined approach with surgical resection followed by chemotherapy. Patients with infection confined to a bursa, and from whom an organism has been isolated to permit definitive susceptibility testing, may be treated with antimicrobials alone and observed for clinical response.

Serum protein binding of weakly acidic drugs is impaired in uremia, but that of basic drugs tends to be normal. Treatment of uremic serum with anion exchange resin (Amberlite CG-400, acetate form) corrected binding defects for three acidic drugs (nafcillin, salicylate and sulfamethoxazole) but did not affect the binding of two basic drugs (trimethoprim and quinidine). Resin treatment of normal human serum did not alter the binding of these five drugs. Extraction of the acetate buffer eluate from resin exposed to uremic serum with n-butyl chloride at acidic pH (3.0) resulted in a fraction that could induce similar binding defects in normal human serum. The factor(s) responsible for binding defects in uremia appears to be lipid soluble, weakly acidic, and dialyzable. It is believed to be tightly bound to albumin at physiologic pH, but dissociates from it at acidic pH. These findings further support the previously proposed hypothesis that drug-binding defects in uremia are due to accumulation of certain endogenous metabolic product(s).

A 57-year-old woman underwent ventriculoperitoneal shunt placement for noncommunicating hydrocephalus. She required several shunt revisions over a 2-year period for recurrent hydrocephalus. The shunt was subsequently found to be obstructed by growth of the saprophytic fungus, Paecilomyces variotii, an infrequent human pathogen. Paecilomyces infections have caused complications associated with prosthetic cardiac valves and synthetic lens implantation; this is the first reported association with a cerebrospinal fluid shunt.

The chemical basis of drug-binding defects in uremia was investigated by studying the effects of extraction of uremic sera with an organic solvent (n-butyl chloride). Extraction of uremic sera at acidic pH (3.0) with n-Butyl chloride fully corrected the binding defects for three acidic drugs (nafcillin, sulfamethoxazole, and salicylate), whereas binding of two basic drugs (trimethoprim and quinidine) was unaffected by similar treatment. When added to normal human serum or purified human serum albumin, the organic solvent layer was capable of inducing binding defects similar to those seen in uremia. Further fractionation of the organic solvent layer with purified human serum albumin at physiologic pH (7.4), followed by reacidification and extraction of the acidified albumin layer with the same solvent, gave a homogeneous fraction on thin-layer chromatography. This homogeneous fraction could induce the binding defects observed in uremia when added to normal human sera. This factor(s) is apparently a dialyzable and weakly acidic compound. It is lipid-soluble and tightly bound to albumin at physiologic pH, but extractable at acidic pH. Its molecular weight is approximately 500 or less. These findings strongly support the hypothesis that the drug-binding defect in uremia is due to accumulation of endogenous metabolic products rather than to an intrinsic structural abnormality in serum albumin.

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 μg/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.

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.