Harold C. Neu

Primary cutaneous aspergillosis in six leukemic children

We report a cluster of primary cutaneous aspergillosis in six children with hematologic malignancy. When first seen, they had hemorrhagic bullae caused by Aspergillus flavus, Aspergillus fumigatus, and Aspergillus niger at the sites of insertion of intravenous cannulas or where arm boards had been taped to the extremities. Rapid diagnosis of cutaneous aspergillosis was made by direct examination of the blister roof with potassium hydroxide before it progressed to a necrotic ulcer. Intravenous amphotericin was instituted promptly in five of six patients, and none died of disseminated aspergillosis. Epidemiologic investigation tracked the source of aspergillus to a storeroom with a false ceiling that had recently been repaired for a water leak.

Acute Interstitial Nephritis due to Amoxicillin Therapy

Acute interstitial nephritis (AIN) has been reported in association with therapy with a number of drugs. We report a patient who developed drug-related AIN while receiving intravenous amoxicillin therapy. The patient developed rash, secondary temperature elevation, and eosinophilia in association with nonoliguric renal failure. Renal biopsy showed evidence for AIN and the renal failure was responsive to corticosteroid therapy. AIN may occur in patients receiving any drug of the penicillin class. This reversible form of acute renal failure must not be overlooked in patients with other forms of renal disease.

β-Lactamases, β-lactamase inhibitors, and skin and skin-structure infections

β -Lactamases have been known since the early 1940s when they were recognized as a major mechanism of resistance in Staphylococcus aureus . The synthesis of semisynthetic penicillins provided agents that overcame the resistance of staphylococci, but as gram-negative bacteria became increasingly important as the cause of infections, plasmid-mediated β -lactamases were recognized in the Entervbacteriaceae, Haemophilus , and chromosomally mediated β -lactamases in Klebsiella , and Bacteroides were found to be the mechanism of resistance of these species to ampicillin and related penicillins. Two approaches to the problem have been developed. One is to make stable compounds. This has been possible in the cephalosporin family. The other method has been to find inhibitors of β -lactamases. Qavulanate is a β -lactamase inhibitor that, in combination with amoxicillin, allows the combination to inhibit many of the organisms that are resistant to amoxicillin. Similarly, clavulanate has been combined with ticarcillin to provide a parenteral agent to inhibit β -lactamase-producing bacteria and retain activity against Pseudomonas . Sulbactam has been combined with ampicillin. The combination of suicide inhibitors with other β -lactams has provided agents that inhibit many of the bacteria present in mixed cutaneous infections. Clinical studies have established the efficacy of the clavulanate-amoxicillin and clavulanate-ticarcillin combinations in skin and skin-structure infections. These agents offer an alternative to other drugs when treating cutaneous infections.

Antimicrobial agents: The old and the new

Although there are many new antimicrobial agents, many of the old antibiotics are still useful in the treatment of infections, particularly those in the community. Antimicrobial resistance patterns and special pharmacologic properties should influence the selection of newer antimicrobial agents. Change from parenteral therapy to oral therapy should increase to avoid the complications of intravenous therapy and to reduce hospital costs. Older antibiotics that are less costly should be used when the etiology and susceptibility of infecting pathogens are known. There will continue to be new antibiotics produced. Understanding the microbiologic and pharmacologic advantages of the new agents compared with older agents is essential if the new agents are to be used properly and not destroyed by inappropriate use.