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Renal Toxicity During Therapy With Gentamicin or Tobramycin
INFECTIONS AND ANTIBIOTICS
I,
Three patients ,vith different of n-no,-o+- symptomatology illustrate the different types of prostatitis. In nonbacterial prostatitis, which is the most common variety of prostatic inflammation, it is difficult to demonstrate the presence of bacterial, fungal parasitic infection. Some patients complain of prostatic pain (prostatodynia) and can be demonstrated to suffer from voiding abnormalities suggestive of bladder-sphincter dyssynergia. If the underlying cause of nonbacterial prostatitis is not known it is not surprising that its care is difficult. In such ca3es therapy is best directed toward symptomatic relief. In bacterial pn, ,tatitis the causative agents are similar in type and prevalence to those responsible for urinary tract infection (Escherichia coli, Proteus, Klebsiella, Enterobacter, Pseudomonas, Serratia and enterococcus). The routes of infection are urethral, reflux of infected urine into prostatic ducts, invasion by rectal bacteria and hematogenous infection. Gonococcal prostatitis occurs in men with a history of gonococcal urethritis. Microscopic examination of prostatic expressate that contains > 10 white blood cells per high power field, as well as lipid-laden macrophages, identify the site of inflammation as the prostate (macrophages are not found in urethral exudates). On ocassion, quantitative cultures of semen may be useful in diagnosing prostatitis when prostatic fluid is difficult to obtain by massage. Serologic studies in men with prostatitis have demonstrated an immune response against the causative bacterial agent. The performance of simultaneous quantitative cultures of the urethra, bladder urine and expressed prostatic secretions is the most useful method of establishing the diagnosis of bacterial prostatitis. Acute bacterial prostatitis produces characteristic signs and symptoms (chills, fever, low back and perinea! pain, general malaise and prostration). Arthralgia, myalgia and intense irritative voiding symptoms, as well as bladder outlet obstructions, are present. Rectally, the prostate is swollen, and its expressate demonstrates pus and yields confluent growth of pathogens on culture. The treatment consists of adequate suprapubic drainage of urine and appropriate antibiotics. Chronic bacterial prostatitis is a common cause of relapsing urinary tract infection in men. It is expressed by various degrees of irritative symptoms, with relapsing and intermittent bacteriuria. The organism persists in prostatic fluid despite therapy because most antibacterial agents diffuse poorly from plasma into prostatic ducts and acini. Chronic calculous prostatitis develops commonly in middleaged and elderly men. In certain men with prostatic stones and relapsing bacteriuria bacterial pathogens within the calculi have proved to be the source of the relapsing bacteriuria. As in patient 3 the removal of these infected calculi surgical means is the only chance for cure. The profound alteration in the composition of prostatic fluid in patients with chronic bacterial prostatitis indicates that a severe generalized secretory dysfunction is present. This secretory dysfunction almost certainly influences the passage of antimicrobial agents into prostatic fluids. The distinctly alkaline prostatic secretions in men with chronic prostatitis inhibit the passage of antimicrobial agents that are bases (such as trimethoprim-sulfamethoxazole) into the prostatic fluid but enhance the passage of other drugs (such as minocycline). Zinc concentrations are lower in men with chronic bacterial prostatitis. Some clinicians advocate the use of oral zinc preparations for treating chronic bacterial prostatitis. It is not known whether the level of zinc in prostatic secretions is increased by the oral
393
administration of the substance. At present, trimethoprim-sulfamethoxazole is the antimicrobic drug with the best documented record of success for the treatment of chronic bacterial prostatitis (cure rates range from 32 to 71 per cent). Other drugs are helpful (erythromycin and minocycline). Surgical treatment by transurethral resection may be curative on occasion. A session of questions and answers followed this presentation. C.E.M. 1 figure, 6 tables, 34 references
Renal Toxicity During Therapy With Gentamicin or Tobramycin
T. F. KEYS, S. B. KURTZ, J. D. JONES AND s. M. MULLER, Divisions of Infectious Diseases, Internal Medicine and Nephrology, Section of Clinical Chemistry, and Department of Laboratory Medicine, Mayo Clinic, Rochester, Minnesota Mayo Clin. Proc., 56: 556-559 (Sept.) 1981 Aminoglycoside toxicity has been recognized since the clinical usage of streptomycin nearly 40 years ago. Gentamicin, a broadspectrum aminoglycoside antibiotic introduced in the 1960s, has well documented renal toxicity. A leading claim for the use of tobramycin in place of gentamicin is that tobramycin is less nephrotoxic. Twenty-seven patients who had normal pre-therapy renal clearance by the 125iodine iothalamate test were assigned randomly either gentamicin or tobramycin for therapy of infections caused by susceptible bacteria. No patient was critically ill or had evidence of bacteremia. Mean age and duration of therapy were 51 years and 14 days, respectively, for 15 patients treated with gentamicin, and 45 years and 13 days for 12 patients treated with tobramycin. At the completion of therapy 6 gentamicin (40 per cent) and 7 tobramycin (58 per cent) patients had a decrease in renal clearance of at least 14 per cent less than baseline. The mean decrease was 26 per cent in the gentamicin group and 23 per cent in the tobramycin group. Simultaneous increases in serum creatinine concentrations (0.2 mg./dl.) occurred in only 4 of the 13 patients (31 per cent). Of 4 patients who had renal clearance studies repeated 3 weeks to 6 months after therapy 2 had stable function but at 16 to 19 per cent less than baseline. Mean urinary concentration of N-acetyl glucosaminidase and alanine aminopeptidase increased faster and to higher levels with gentamicin than with tobramycin. However, on an individual patient basis they were not predictive of a decrease in renal clearance in either therapy group. The authors recommend that serum concentrations of creatinine be monitored every 2 to 3 days in patients with normal renal function and more frequently if significant elevations in serum concentrations of creatinine occur. In addition, advise that serum peak and trough antibiotic concentrations be checked at least 1 or 2 times a week in patients who are being treated with either gentamicin or tobramycin. W. W.K. 4 tables, 15 references
Effect of Potassium Depletion on Gentamicin Nephrotoxicity
K. R. BRINKER, R. E. BULGER, D. C. DOBYAN, T. R. STACEY, P. M. SOUTHERN, W. L. HENRICH AND R. E. CRONIN, Department of Medicine, Veterans Administration Medical Center and University of Texas Southwestern Medical School, Dallas, and Department of Pathology and Labora-
I,
Three patients ,vith different of n-no,-o+- symptomatology illustrate the different types of prostatitis. In nonbacterial prostatitis, which is the most common variety of prostatic inflammation, it is difficult to demonstrate the presence of bacterial, fungal parasitic infection. Some patients complain of prostatic pain (prostatodynia) and can be demonstrated to suffer from voiding abnormalities suggestive of bladder-sphincter dyssynergia. If the underlying cause of nonbacterial prostatitis is not known it is not surprising that its care is difficult. In such ca3es therapy is best directed toward symptomatic relief. In bacterial pn, ,tatitis the causative agents are similar in type and prevalence to those responsible for urinary tract infection (Escherichia coli, Proteus, Klebsiella, Enterobacter, Pseudomonas, Serratia and enterococcus). The routes of infection are urethral, reflux of infected urine into prostatic ducts, invasion by rectal bacteria and hematogenous infection. Gonococcal prostatitis occurs in men with a history of gonococcal urethritis. Microscopic examination of prostatic expressate that contains > 10 white blood cells per high power field, as well as lipid-laden macrophages, identify the site of inflammation as the prostate (macrophages are not found in urethral exudates). On ocassion, quantitative cultures of semen may be useful in diagnosing prostatitis when prostatic fluid is difficult to obtain by massage. Serologic studies in men with prostatitis have demonstrated an immune response against the causative bacterial agent. The performance of simultaneous quantitative cultures of the urethra, bladder urine and expressed prostatic secretions is the most useful method of establishing the diagnosis of bacterial prostatitis. Acute bacterial prostatitis produces characteristic signs and symptoms (chills, fever, low back and perinea! pain, general malaise and prostration). Arthralgia, myalgia and intense irritative voiding symptoms, as well as bladder outlet obstructions, are present. Rectally, the prostate is swollen, and its expressate demonstrates pus and yields confluent growth of pathogens on culture. The treatment consists of adequate suprapubic drainage of urine and appropriate antibiotics. Chronic bacterial prostatitis is a common cause of relapsing urinary tract infection in men. It is expressed by various degrees of irritative symptoms, with relapsing and intermittent bacteriuria. The organism persists in prostatic fluid despite therapy because most antibacterial agents diffuse poorly from plasma into prostatic ducts and acini. Chronic calculous prostatitis develops commonly in middleaged and elderly men. In certain men with prostatic stones and relapsing bacteriuria bacterial pathogens within the calculi have proved to be the source of the relapsing bacteriuria. As in patient 3 the removal of these infected calculi surgical means is the only chance for cure. The profound alteration in the composition of prostatic fluid in patients with chronic bacterial prostatitis indicates that a severe generalized secretory dysfunction is present. This secretory dysfunction almost certainly influences the passage of antimicrobial agents into prostatic fluids. The distinctly alkaline prostatic secretions in men with chronic prostatitis inhibit the passage of antimicrobial agents that are bases (such as trimethoprim-sulfamethoxazole) into the prostatic fluid but enhance the passage of other drugs (such as minocycline). Zinc concentrations are lower in men with chronic bacterial prostatitis. Some clinicians advocate the use of oral zinc preparations for treating chronic bacterial prostatitis. It is not known whether the level of zinc in prostatic secretions is increased by the oral
393
administration of the substance. At present, trimethoprim-sulfamethoxazole is the antimicrobic drug with the best documented record of success for the treatment of chronic bacterial prostatitis (cure rates range from 32 to 71 per cent). Other drugs are helpful (erythromycin and minocycline). Surgical treatment by transurethral resection may be curative on occasion. A session of questions and answers followed this presentation. C.E.M. 1 figure, 6 tables, 34 references
Renal Toxicity During Therapy With Gentamicin or Tobramycin
T. F. KEYS, S. B. KURTZ, J. D. JONES AND s. M. MULLER, Divisions of Infectious Diseases, Internal Medicine and Nephrology, Section of Clinical Chemistry, and Department of Laboratory Medicine, Mayo Clinic, Rochester, Minnesota Mayo Clin. Proc., 56: 556-559 (Sept.) 1981 Aminoglycoside toxicity has been recognized since the clinical usage of streptomycin nearly 40 years ago. Gentamicin, a broadspectrum aminoglycoside antibiotic introduced in the 1960s, has well documented renal toxicity. A leading claim for the use of tobramycin in place of gentamicin is that tobramycin is less nephrotoxic. Twenty-seven patients who had normal pre-therapy renal clearance by the 125iodine iothalamate test were assigned randomly either gentamicin or tobramycin for therapy of infections caused by susceptible bacteria. No patient was critically ill or had evidence of bacteremia. Mean age and duration of therapy were 51 years and 14 days, respectively, for 15 patients treated with gentamicin, and 45 years and 13 days for 12 patients treated with tobramycin. At the completion of therapy 6 gentamicin (40 per cent) and 7 tobramycin (58 per cent) patients had a decrease in renal clearance of at least 14 per cent less than baseline. The mean decrease was 26 per cent in the gentamicin group and 23 per cent in the tobramycin group. Simultaneous increases in serum creatinine concentrations (0.2 mg./dl.) occurred in only 4 of the 13 patients (31 per cent). Of 4 patients who had renal clearance studies repeated 3 weeks to 6 months after therapy 2 had stable function but at 16 to 19 per cent less than baseline. Mean urinary concentration of N-acetyl glucosaminidase and alanine aminopeptidase increased faster and to higher levels with gentamicin than with tobramycin. However, on an individual patient basis they were not predictive of a decrease in renal clearance in either therapy group. The authors recommend that serum concentrations of creatinine be monitored every 2 to 3 days in patients with normal renal function and more frequently if significant elevations in serum concentrations of creatinine occur. In addition, advise that serum peak and trough antibiotic concentrations be checked at least 1 or 2 times a week in patients who are being treated with either gentamicin or tobramycin. W. W.K. 4 tables, 15 references
Effect of Potassium Depletion on Gentamicin Nephrotoxicity
K. R. BRINKER, R. E. BULGER, D. C. DOBYAN, T. R. STACEY, P. M. SOUTHERN, W. L. HENRICH AND R. E. CRONIN, Department of Medicine, Veterans Administration Medical Center and University of Texas Southwestern Medical School, Dallas, and Department of Pathology and Labora-