Antibiotic Combinations

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INFECTIONS AND ANTIBIOTICS

ointment as a time-limited local treatment of recurrent herpes simplex of the lips and genitals. Since the rate of recurrence after interferon-{) is reduced this may result in less reinfection of neurons by the ascending route because of a decrease in virus load or other mechanism. 1 table, 34 references Francisco T. Aledia, M.D. Columbus, Ohio

Single-Dose v. Short-Term Antibiotic Therapy for Prevention of Wound Infection in General Surgery. A Prospective, Randomized Double-Blind Trial H. J. M. 00STVOGEL, T. J. M. V. VAN VROONHOVEN, C. VAN DER WERKEN AND A. W. LENDERINK, Depart-

ments of Surgery and Clinical Pharmacology, St. Elizabeth Hospital, Tilburg, The Netherlands Acta Chir. Scand., 153: 571-575 (Oct.) 1987

Clindamycin

A. S. KLAINER, Department of Internal Medicine, Morristown Memorial Hospital, Morristown, New Jersey, and Department of Clinical Medicine, College of Physicians and Surgeons, Columbia University, New York, New York Med. Clin. N. Amer., 71: 1169-1175 (Nov.) 1987 Clindamycin is a derivative of the amino acid trans-L-4-npropylhygrinic acid, attached to a sulfa-containing derivative of an octose, and the 7-deoxy, 7-chloro derivative of lincomycin. It binds exclusively to the 50 s subunit of bacterial ribosomes and suppresses intracellular protein synthesis. Clindamycin is inactivated by metabolism to N-demethyl-clindamycin and clindamycin sulfoxide, which are excreted in the urine and bile. It is absorbed almost completely after oral administration with a peak concentration within 1 hour after ingestion. When given intravenously the peak levels are reached in 20 to 45 minutes. About 10 per cent of the clindamycin is excreted unaltered in the urine and small quantities are excreted in the feces. The antibacterial activity of clindamycin persists in the feces for 5 or more days after discontinuation of parenteral therapy, so that the growth of sensitive microorganisms in the colon remains suppressed for up to 2 weeks, which may explain the delayed onset of clindamycin-associated colitis. Since clindamycin can accumulate in patients with impaired renal function and severe hepatic dysfunction the dose should be adjusted. Clindamycin is effective against Streptococcus pneumoniae, Strept. pyogenes, Strept. viridans, many strains of Staphylococcus aureus and many anaerobic bacteria, including Bacteroides fragilis. It should be emphasized that pseudomembranous colitis associated with the use of clindamycin is far less frequent than previously believed. Cephalosporins, tetracycline and ampicillin cause antibiotic-associated colitis with a higher frequency. If diarrhea or colitis occurs with clindamycin it should be discontinued immediately. If diarrhea persists 125 to 500 mg. vancomycin orally every 6 hours for 7 to 10 days are effective in reducing the diarrhea and fatality. Oral metronidazole and bacitracin also may be effective. Agents that inhibit peristalsis, such as diphenoxylate hydrochloride plus atropine, may cause worsening of the colitis because they extend the time that toxin is in contact with the mucosal surface of the gastrointestinal tract. Clindamycin has been used with great success in cases of streptococcal pharyngitis, anaerobic infections, pelvic inflammatory disease, acne and osteomyelitis. The author concludes that clindamycin is an excellent, well tolerated, effective antimicrobial agent against specific anaerobic infections, and infection caused by Staph. aureus and anaerobes. 28 references Francisco T. Aledia, M.D. Columbus, Ohio

A prospective, randomized double-blind trial was conducted in 564 patients undergoing a clean-contaminated, contaminated or clean (vascular) operation to compare the effectiveness of single-dose therapy with short-term prophylaxis in the prevention of postoperative wound infection. There were 277 patients in the short-term antibiotic group (1 dose preoperatively and 2 doses postoperatively) and 287 in the single-dose group (preoperative). The antibiotics used were penicillin, tobramycin and metronidazole in various combinations. Wound infections occurred in 5 of the 277 patients (1.8 per cent) in the shortterm antibiotic group and 9 of the 287 (3.1 per cent) in the single-dose group. The difference was not statistically significant. This study indicates that single-dose antibiotic prophylaxis is sufficient to minimize wound infection after cleancontaminated and contaminated operations, as well as after a vascular procedure. 5 tables, 16 references Francisco T. Aledia, M.D. Columbus, Ohio

Antibiotic Combinations J. D. ALLAN, JR., Harvard Medical School and Infectious Diseases Section, New England Deaconess Hospital, Boston, Massachusetts Med. Clin. N. Amer., 71: 1079-1091 (Nov.) 1987 It is common practice among physicians who treat known or suspected infections to use a combination of antimicrobial agents. The rationales are to provide broad-spectrum coverage in certain seriously ill patients when the causative agent is unknown, treat polymicrobial infections when the spectrum of a single agent is not sufficient to provide activity against all involved organisms, enhance the inhibition or killing of a given bacterial pathogen over that achievable by a single agent, decrease the potential for resistance developing to a single agent while on therapy and, less commonly, allow a decrease in the dose of a toxic agent. It is important to remember that a drug combination may increase the incidence of side effects and the cost of treatment, and it may potentially result in decreased clinical efficacy owing to interference of the activity of one agent by the second agent. It is possible for an antibiotic combination to exhibit less activity than either agent used alone, and lead to colonization and superinfection with resistant organisms, and to an increased risk of toxic side effects. Although reports have indicated that the use of an antibiotic combination has been superior to single-agent therapy in a number of clinical situations, the incidence of these findings is less frequent than most physicians realize. With the recent advancement in more potent antibiotics against a broad-spectrum bacteria it is possible that some of these new drugs may be sufficient to replace the antibiotic combination. If combination therapy is to be used it should be changed to the safest,

ONCOLOGY AND CHEMOTHERAPY

simplest and least expensive agent as soon as the identity and susceptibility of the infecting organism are known. 2 tables, 20 references Francisco T. Aledia, M.D. Columbus, Ohio

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cocci and streptococeal endocarditis. These drugs are not bactericidal and they should be combined with an aminoglycoside. The author makes some interesting and thoughtful predictions of the future of antimicrobials. 3 tables, 13 references John A. Arcadi, M.D. Whittier, California

Antimicrobial Agents: A Widening Choice

R.

WISE, Department of Medical Microbiology, Dudley Road Hospital, Birmingham, United Kingdom

Lancet, 2: 1251-1254 (Nov. 28) 1987 A detailed evaluation of antimicrobials currently being used and others that will be available shortly is presented. The "penams" or penicillins have had few recent additions. However, combinations of amoxicillin or ticarcillin with the /3lactamase inhibitor clavulanic acid presently are available. Although effective against such organisms as Bacteroides fragilis, certain other bacteria can produce a {3-lactamase that is not or poorly inhibited by clavulanic acid and, thus, resistant to the penam combinations. By combining ticarcillin/clavulanic acid with an aminoglycoside an effective method to treat infections in the immunocompromised patient may be developed. Temocillin is a new agent with a narrow spectrum for nosocomial gram-negative sepsis. It still is under investigation. The antipseudomonal drugs piperacillin, mezlocillin and axlocillin are used widely but they are susceptible to bacterial lactamases. Azlocillin is the best penicillin to treat Pseudomonas aeruginosa infections. The "penems" are semi-synthetic compounds, of which imipenem is available in the United States. Other similar drugs are being studied as either injectable, such as imipenem, or an oral agent. Imipenem is given with a dihydropeptidase inhibitor, cilastatin, which interferes with the renal metabolism of imipenem and reduces its renal toxicity. This drug combination has a broad spectrum, including gram-positive organisms and the gram-negative bacilli, such as P. aeruginosa and Hemophilus influenzae. In the same group the drugs aztreonam and carumonam are under investigation. In the "cephems" or cephalosporins, cefamycins and oxacephems there are significant new additions, such as cefixime, cefuroxime axetil, ceftazidime and ceftriaxone. Cefixime is an oral agent with an effective range similar to early parenteral agents of similar structure. Cefuroxicime is the most widely used parenteral agent in this group in the United Kingdom and it is satisfactory for therapy and prophylaxis. Cefuroxime axetil is an oral agent not yet released that if tolerated should be most useful. Ceftazidine alone has a reliable and high degree of activity against P. aeruginosa. Ceftriaxone has an 8-hour halflife allowing once or twice daily administration. While aminoglycosides remain popular no new such drugs are on the market. Increasing resistance has been apparent in European studies with up to 30 per cent of the blood culture isolates in Italy being resistant to gentamicin. Because of continuing problems and questions of nephrotoxicity and ototoxicity the serum levels should be monitored when the aminoglycosides are used. Erythromycin is a macrolide antimicrobial agent for which similar agents are being sought with less side effects. Somewhat lower evidence of side effects is noted with the drug roxithromycin, an oxime derivative of erythromycin. Teicoplanin is a glycopeptide that appears to be more active than vancomycin. This group of drugs is used for methicillin-resistant staphylo-

ONCOLOGY AND CHEMOTHERAPY Renal Cell Carcinoma in Patients With Tuberous Sclerosis M. E. WEINBLATT, E. KAHN AND J. KOCHEN, Departments of Pediatrics and Pathology, Cornell University Medical College, New York, and Departments of Laboratories and Pediatrics, and Division of Pediatric Hematology/Oncology, North Shore University Hospital, Manhasset, New York

Pediatrics, 80: 898-903 (Dec.) 1987 An adolescent with anemia and weight loss at evaluation had bilateral renal cell carcinoma. Further investigation revealed underlying tuberous sclerosis that had escaped previous clinical detection. A review of the literature revealed 6 similar cases of remarkable similarity. In all cases tuberous sclerosis was in an incomplete form that had escaped recognition. In each case the tumor had a relatively benign nature, since none of the patients had metastatic disease during a median followup of 3½ years after surgical treatment alone. While neurocutaneous syndromes traditionally are associated with hamartomatous tumors at various anatomical areas, this case and the review of the literature confirm the association of renal cell carcinoma with tuberous sclerosis. 1 figure, 1 table, 38 references William J. Cromie, M.D. Albany, New York

Editorial comment. Renal cystic disease also is common in children with tuberous sclerosis. Renal failure may ensue. If such patients require dialysis and transplantation the native kidney should be removed. Lowell R. King, M.D. Durham, North Carolina

Female Urethral Cancer-An Overview V. SRINIVAS AND S. A. KAHN, Department of Urology, State University of New York at Stony Brook and Veterans Administration Medical Center, Northport, New York

Int. Urol. Nephrol., 19: 423-428, 1987 Female urethral cancer is a rare urological malignancy that accounts for 0.02 per cent of all malignancies in female patients and 1 per cent of all female genitourinary malignancies. The average patient age at diagnosis is 61 years, with a range of 29 to 90 years. The etiology is unclear. Trauma of sexual intercourse, childbearing or infection may be predisposing factors, since it is seen more commonly in postmenopausal, multiparous women. The most common presenting symptom is urethral bleeding or spotting but some patients may present with irritative or obstructive urinary symptoms and dyspareunia. Late manifestations of urethral cancer are pelvic pain, weight loss, periure-