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NOTES Cefotiam Therapy of Lower Respiratory Tract Infections MICHAEL A

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NOTES Cefotiam Therapy of Lower Respiratory Tract Infections MICHAEL A ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Oct. 1985, p. 576-577 Vol. 28, No. 4 0066-4804/85/100576-02$02.00/0 Copyright C) 1985, American Society for Microbiology NOTES Cefotiam Therapy of Lower Respiratory Tract Infections MICHAEL A. POLIS AND CARMELITA U. TUAZON* Department of Medicine, Division ofInfectious Diseases, George Washington University Medical Center, Washington, D.C. 20037 Received 26 December 1984/Accepted 7 July 1985 Cefotiam, a new cephalosporin, was evaluated in the treatment of lower respiratory tract infections in 29 patients. The bacteria isolated from the sputum of these patients included Streptococcus pneumoniae (31%), Kkbsiella pneumoniae (31%), and Haemophilus influenzae (28%). Satisfactory response was observed in 90% of the patients. There were three treatment failures, two superinfections, and four colonizations with gram-negative organisms resistant to the drug. Superficial phlebitis was noted in two patients. The results of this study suggest that cefotiam is an effective and well-tolerated antibiotic for the treatment of lower respiratory tract infections due to susceptible organisms. Cefotiam, a new semisynthetic cephalosporin, has a broad per high-power field as determined with Gram stain) were spectrum of activity against most gram-positive organisms as obtained from all patients for Gram stain and culture (3). well as gram-negative aerobic bacilli such as Klebsiella, Chest roentgenograms and blood cultures were performed Proteus, Haemophilus, Enterobacter, and Citrobacter spe- before therapy and were repeated as deemed appropriate. cies (5, 7, 9). The antibiotic is also active against I- Cure was defined as complete eradication of the signs and lactamase-producing strains of Staphylococcus aureus and symptoms of acute lower respiratory tract infection with Haemophilus influenzae (9). Cefotiam has been shown to bacteriologic clearance. Improvement was defined as allevi- attain high levels in the lung tissue of animals (8). Because of ation of the signs and symptoms with or without bacterio- its antimicrobial spectrum, we evaluated the efficacy and logic clearance. All bacterial isolates from patients were safety of the drug in the treatment of lower respiratory tract tested for susceptibility to cefotiam with a 30-,ug disk, using infections. the standard disk diffusion technique (1). Hospitalized patients 18 years of age or older requiring Chest roentgenograms were obtained on 35 patients upon parenteral antibiotics were entered into the study. Consent admission. Of the 29 evaluable patients, all had infiltrates on was obtained from all patients. Selection criteria for these chest roentgenograms except for 1 patient with severe bron- studies included patients (i) with a presumptive diagnosis of chitis. A total of 20 patients had lobar pneumonia, 5 patients acute pulmonary infection based on the presence of fever, had bronchopneumonia, and 1 patient each had lobar pneu- cough, dyspnea, and infiltrate on chest roentgenogram, and monia with empyema, lobar pneumonia with a lung abscess, (ii) with moderate to abundant gram-positive cocci, gram- and an infiltrate compatible with aspiration pneumonia. A negative bacilli, or gram-negative coccobacilli and polymor- total of six patients were not evaluable; two patients of the phonuclear leukocytes on Gram stain examination of the nonevaluable group had Pseudomonas aeruginosa isolated sputum. Exclusion criteria included patients (i) with an from their sputum cultures and required broader antibiotic allergy to cephalosporins, penicillins, or local anesthetics of therapy, one patient had severe chronic obstructive lung the amide type, (ii) with hepatic dysfunction with a serum disease with H. influenzae pneumonia and died on day 3 of bilirubin or serum glutamic oxalacetic transaminase greater therapy, one patient had congestive heart failure with S. than twice normal, (iii) with renal impairment with a serum aureus pneumonia and died on day 3 of therapy, one patient creatinine greater than twice normal, (iv) who received developed meningitis and required a change in therapy after antimicrobial therapy within the previous 48 h, (v) with the one dose of cefotiam, and one patient had pulmonary edema need for concomitant antimicrobial therapy, (vi) who were rather than pneumonia and received one dose of cefotiam. pregnant, (vii) with impaired immunologic function receiving A total of 29 patients, 21 men and 8 women (age range, 23 immunosuppressive therapy, and (viii) who were seriously ill to 92 years; mean age, 60), with lower respiratory tract and were likely to die within 72 h. infections were evaluated. Eighteen patients had more than The dosage of cefotiam varied from 0.5 g every 6 h to 2 g one underlying disease. Only two patients had no significant every 6 h, depending on the severity of the illness. The underlying disease. patient must have received at least 4 days of cefotiam The bacteria isolated from the 29 patients in the study are therapy to be considered evaluable. Pathogens isolated summarized in Table 1. Forty-four pathogenic bacteria were before therapy had to be susceptible to cefotiam. isolated from the 29 patients. More than one organism was Patients were followed and examined daily through the isolated from 19 patients. In five patients the diagnosis of end of therapy. Hematologic, hepatic, and renal function Streptococcus pneumoniae pneumonia was made on the tests were performed. Adequate sputum specimens (contain- of the cells basis of the characteristic morphology on Gram stains ing more than 25 leukocytes and less than 10 epithelial sputa, the infiltrates on chest roentgenograms, and clinical presentation. None of these patients was bacteremic. * Corresponding author. There was a satisfactory clinical response in 26 of 29 576 VOL. 28, 1985 NOTES 577 TABLE 1. Bacterial etiology of 29 cases of lower respiratory colonized with gram-negative organisms, three of them with tract infections and outcome of therapy with cefotiam P. aeruginosa. No. of Cefotiam is a new broad-spectrum cephalosporin with an that In Bacterial etiology(n.rsoepatients % Satisfactory in vitro spectrum similar to of cefamandole (5, 7, 9). (no. response contrast to cefamandole, which required more frequent bacteremic) administration, clinical and bacteriologic cures have been Streptococcus pneumoniae 14 (2)a 93b reported in a study of skin and soft-tissue infections in which Klebsiella pneumoniae 9 78b,c cefotiam was administered every 12 h (2). In animal studies, Haemophilus influenzae 8 (1) 88b cefotiam attains very high tissue concentrations in the kid- Citrobacter sp. 2 100 neys, liver, and lungs (8). The therapeutic efficacy of Pseudomonas aeruginosa 2d 100 cefotiam may be due to its high affinity for penicillin-binding Staphylococcus aureus 2 100 proteins (4). Escherichia coli 2 100 was a and Serratia sp. 2 100 In this study, cefotiam safe, well-tolerated, Enterobacter sp. 2 50c effective antibiotic for non-life-threatening lower respiratory Enterobacter agglomerans 1 oe tract infections, with a low incidence of adverse effects. A Pseudomonas sp. (not P. 1 oe disturbing problem was the relatively large number of aeruginosa) posttherapy superinfections (2) and colonizations (3) that Enterobacter cloacae 1 100 were caused by P. aeruginosa. This may pose a problem in Proteus mirabilis 1 100 the treatment of pneumonia in seriously ill patients in Pseudomonas maltophilia 1 100 situations such as an intensive-care-unit setting, where Beta-hemolytic streptococcus, 1 100 superinfection is common (6). Nevertheless, in lower respi- non-group A ratory tract infections due to susceptible organisms, when a Five cases were diagnosed by Gram stains, chest roentgenograms, and aminoglycosides must be avoided, cefotiam is an alternative clinical presentation. drug that can be administered safely to mildly to moderately b One failure had mixed S. pneumoniae-K. pneumoniae-H. influenzae a is indicated. Further pneumonia. ill patients when parenteral antibiotic c One failure had mixed K. pneumoniae-Enterobacter pneumonia. studies are warranted to determine whether cefotiam can be d Obtained from a single patient with chronic bronchitis. administered every 8 or 12 h in the therapy of lower ' One failure had mixed E. agglomerans-Pseudomonas (not P. aeruginosa) respiratory tract infections. pneumonia. LITERATURE CITED 1. Bauer, A. W., W. M. M. Kirby, J. C. Sherris, and M. Turus. patients (90%); 8 patients were cured, and 18 patients 1966. Antibiotic susceptibility testing by a standardized single improved with completion of cefotiam therapy as assessed disk method. Am. J. Clin. Pathol. 45:493-496. by clinical parameters and chest roentgenograms. The latter 2. Lentino, J. R., M. Stachowski, R. Strikas, and P. Parrillo. 1984. 18 patients received further oral therapy after parenteral Comparative efficacy of cefotiam versus cephalothin in the therapy of skin and soft tissue infections. Antimicrob. Agents therapy to complete a minimum of a 10-day course of Chemother. 25:778-780. antibiotics. The oral therapy was individualized to the spe- 3. Murray, P. R., and J. A. Washington. 1979. Microscopic and cific organism isolated from each patient and included oral bacteriologic analysis of expectorated sputum. Mayo Clin. Proc. penicillin, ampicillin, amoxicillin, cephalexin, or cefaclor. 50:339-344. The duration of cefotiam therapy ranged from 4 to 14 days, 4. Nozaki, Y., A. Imada, and M. Yoneda. 1979. SCE-963, a new with a mean of 7 days. potent cephalosporin with high affinity for penicillin-binding
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