Zinc is a trace metal with in vitro activity against rhinovirus, the major etiologic agent in acute upper respiratory tract infections (URIs). A previous trial of zinc gluconate supported its efficacy in treating URIs, but the effectiveness of blinding was uncertain. We conducted a prospective randomized trial of zinc gluconate versus a taste-matched placebo of sucrose octaacetate. Lozenges containing either 23 mg of elemental zinc or placebo were taken every 2 h. Eleven URI symptoms were rated daily on a scale of 0 (not present) to 3 (severe). Duration of illness, reflected in the proportion of subjects remaining symptomatic on each day, was not significantly reduced (maximum difference of 12.6% on day 7, P = 0.09; 95% confidence interval, -6 to 31%) by either treatment. Severity of illness, assessed by using a summed severity score, was reduced incrementally by 7 to 8% on days 5 to 7 (P = 0.02) in subjects taking zinc. Adverse effects, mostly nausea and altered taste, were reported by 50% of subjects taking zinc. We conclude that while zinc gluconate may produce a small reduction in overall severity of symptoms, this is not clinically significant. Given the additional high incidence of adverse effects, zinc gluconate cannot be recommended for use in the treatment of acute URIs.
Kinetics of gentamicin inactivation by carbenicillin and ticarcillin were studied in vitro and in 17 patients with renal failure. In vitro, the half-life of carbenicillin in human serum at 37 C is longer (19.2 ± 0.7 h) than ticarcillin (7.2 ± 0.6 h). Thus, incubation of gentamicin with equal concentrations of ticarcillin or carbenicillin results in greater inactivation of aminoglycoside activity by the latter. If concentrations of the two penicillins are held equal by repetitive addition, rates of gentamicin inactivation are the same.The serum half-life of gentamicin in patients serving as their own controls was significantly reduced by administration of either penicillin. After carbenicillin, the half-life decreased from 46 ± 8 h to 22 ± 3 h (P < 0.02). The constant for inactivation of gentamicin (ks) by carbenicillin was 0.02 h-1. The results indicate that gentamicin requirements are underestimated by methods currently employed to calculate dosage for patients with renal failure who receive carbenicillin concurrently. Adjustment of gentamicin dosage in such cases by application of the ki for gentamicin is suggested.The antibiotic combination of an aminoglycoside and a penicillin or cephalosporin is frequently administered to provide broad antibacterial therapy for patients with sepsis. In particular, the combination of gentamicin and carbenicillin is employed for treatment of infections caused by Pseudomonas aeruginosa. Although clinical proof is lacking for the superiority of combined over single agent therapy in these infections, the simultaneous use of both antibiotics is favored by many clinicians (2).Most, if not all, penicillins have the capacity to inactivate gentamicin in vitro at a rate that is dependent upon temperature, concentration, and medium composition (20,22). The reaction is thought to occur via nucleophilic opening of the (&lactam ring, probably by the methylamino group ofgentamicin with concomitant formation ofa biologically inactive amide (3, 27; P. G. Daniels, personal communication). As a rule, penicillins must be present for several hours in concentrations at least fivefold greater than those of gentamicin before inactivation of the latter can be demonstrated (20).In clinical practice, such inactivation is observed most frequently when gentamicin and a penicillin are inadvertently mixed in the same bottle of parenteral solution, which is then hung for slow intravenous (i.v.) infusion. Ofthe penicillins administered concurrently with gentamicin, carbenicillin is most frequently given in sufficient dosage to achieve peak serum levels of at least 100 ,ug/ml, thereby exceeding concentrations of the aminoglycoside by more than fivefold. Nevertheless, little or no destruction of aminoglycoside activity can be demonstrated in patients with normal renal function if the two antibiotics are given by separate routes. In patients with renal failure, however, the serum half-lives (t112) of gentamicin and carbenicillin are greatly prolonged (13,28). Thus, repetitive administration of carbenicillin to...
Eleven patients with systemic mycotic infections were treated with amphotericin B, 1 mg/kg, on alternate days. Five patients also received mannitol (M), 1 g/ kg, in the amphotericin infusion, while six served as controls (C). Renal function studies prior to therapy were repeated at a total cumulative amphotericin B dosage of 25 mg/kg; renal biopsies were obtained from 10 patients. Inulin and creatinine clearances decreased in both the C and M groups, significantly so in the latter. Urinary concentrating ability of five patients (2C, 3M) decreased as did the capacity of three (1C, 2M) to acidify urine after an acid load. Neither the peak and valley levels of amphotericin B in serum nor the urinary excretion thereof differed between the C and M groups. Striking vacuolization of smooth muscle cells, previously unrecognized, was observed in the media of arterioles and arteries in all renal biopsies. Tubular calcification was present in both groups. In summary, M therapy (1 g/kg) did not protect against the nephrotoxicity of amphotericin B. A unique lesion of the renal vasculature secondary to amphotericin B is described.Many of the side effects associated with amphotericin B therapy can be ameliorated by therapy every other day and by judicious cotherapy with such agents as heparin, corticosteroids, and antiemetics. Unfortunately, there has been little success in reducing the nephrotoxic effects that often restrict therapy. These include reduction in glomerular filtration rate (GFR) and renal blood flow (5, 24) and abnormalities of distal tubular function. The latter are manifested histologically by intratubular and interstitial calcium deposition (25) and functionally by impaired urinary concentrating ability (13), and by renal tubular acidosis with secondary potassium wasting (4,5,17).Although individual susceptibility to the nephrotoxicity of amphotericin B appears to vary widely (18), the likelihood of at least transient renal impairment is high with the large dose (1.5 to 2.5 g) usually required to treat adequately many of the systemic mycotic infections (5). It has been suggested that alkali therapy might prevent some aspects of amphotericin B nephrotoxicity (17), and in an experimental rat model administration of bicarbonate during amphotericin therapy was shown to improve several measures of renal function (11). Unfortunately, similar studies in man are not available.More recently, it has been reported that administration of an osmotic diuretic, mannitol, significantly reduces the nephrotoxicity of acute amphotericin B administration to dogs (12). Mannitol therapy appeared to prevent a rise in the blood urea nitrogen and serum creatinine (Cr) values as well as the degeneration of renal tubular epithelium that occurred when amphotericin B was administered alone. Clinically, mannitol has been employed extensively as cotherapy with amphotericin B, and protective effects on the kidney have been claimed in one small uncontrolled study (20). Because of widespread interest in the therapeutic potential of mannitol (...
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