A comparison of imipenem to ceftazidime with or without amikacin as empiric therapy in febrile neutropenic patients.

BACKGROUND: Neutropenic patients with cancer are traditionally treated with empiric antibiotic combinations when they become febrile. The availability of broad-spectrum antibiotics such as ceftazidime and imipenem has made it possible to initiate therapy with a single agent (monotherapy). The objectives of this trial were to compare ceftazidime and imipenem as single agents for the therapy of febrile episodes in neutropenic patients and to ascertain whether the addition of an aminoglycoside (amikacin) to either of these agents would provide an advantage. METHODS: A prospective clinical trial was conducted in which eligible neutropenic patients with cancer were randomized to one of four treatment arms: ceftazidime alone; imipenem alone; ceftazidime plus amikacin; and imipenem plus amikacin. Efficacy analysis was done for 750 assessable episodes. A multivariate logistic-regression analysis was also performed to examine the unique contribution of various prognostic factors. RESULTS: The overall response rates were 76% with imipenem plus amikacin, 72% with imipenem, 71% with ceftazidime plus amikacin, and 59% with ceftazidime alone. Single-organism gram-positive infections occurred in 101 of 750 episodes. Without a change in antibiotics, the response rates were 50% with imipenem, 40% with imipenem plus amikacin, 39% with ceftazidime plus amikacin, and 38% with ceftazidime. Most responded to vancomycin or other antibiotics, and the mortality associated with gram-positive infections was only 5%. Regardless of the antibiotic regimen, the majority of uncomplicated gram-negative infections responded to therapy and the majority of complicated gram-negative infections failed to respond. Multivariate logistic-regression analysis showed that recovery of the neutrophil count was the most favorable prognostic factor in a patient's response to infection, whereas the presence of gram-positive infection, acute leukemia, pulmonary or enteric infection, and therapy with ceftazidime were unfavorable factors. CONCLUSIONS: Single-agent therapy with imipenem is as effective as more conventional combination antibiotic therapy for the empirical treatment of febrile episodes in neutropenic patients with cancer.

Serratia bacteremia: review of 118 cases.

A review was conducted of 118 episodes of serratia bacteremia in cancer patients during a 16-year period. The infection occurred most commonly in patients with acute leukemia. Most patients acquired the infection in the hospital, and 61% had received antibiotic therapy during the preceding 10 days. Fever occurred in 90% of cases and shock in 18%. Thirty-eight percent of patients had concomitant pneumonia. Patients with shock, pneumonia, or hemorrhage had a substantially poorer prognosis. The response rate was 75% for patients who received appropriate antibiotics, 22% for those who received inappropriate antibiotics, and 29% for those who received no antibiotics. Patients who continued to have positive blood culture results while receiving appropriate antibiotic therapy had a poor diagnosis. Patients who received only an aminoglycoside had the poorest response rate among those who received appropriate therapy.

Spectrum and outcome of microbiologically documented listeria monocytogenes infections in cancer patients.

At the M.D. Anderson Cancer Center (Houston), Listeria monocytogenes was cultured from 14 patients between 1980 and 1987. The case records of 11 of these patients were reviewed. Underlying malignancies included acute leukemia (three), lymphoma (two), myeloma (one), adenocarcinoma of colon (two), carcinoma of breast (one), carcinoma of lung (one), and Kaposi's sarcoma associated with the acquired immune deficiency syndrome (one). Listeria monocytogenes was cultured from blood (eight patients), cerebrospinal fluid (CSF) (two patients), and from both blood and CSF in one patient. All patients were receiving immunosuppressive therapy including corticosteroids in seven. An absolute neutrophil count of less than 1000/mm3 was noted in five. Bacteremia was the predominant type of infection and ten patients responded to antimicrobial therapy.

Haemophilus species bacteremia in patients with cancer. A 13-year experience.

We reviewed the clinical and laboratory presentation of Haemophilus species bacteremia at our institution, with special attention to predisposing and prognostic factors. Of 36 cases, 18 presented with pneumonia, 1 with cellulitis, and another with sinusitis. No cases of meningitis or endocarditis were detected. Most episodes were caused by Haemophilus influenzae, and the overall response rate to treatment was 72%. Factors including chronic obstructive pulmonary disease, alcoholism, prior splenectomy, and neutropenia did not play an important role in these patients' infections. Most of the isolates serotyped were found to be nontypable. The occurrence of ampicillin resistance was 6% throughout the study. Ampicillin, chloramphenicol, and second-generation cephalosporins were all effective therapeutic regimens. Bacteremia due to Haemophilus species remains an uncommon infection in patients with cancer, despite the predominance of traditional predisposing factors.

Nocardial infection in patients with neoplastic disease.

During the 13 years from 1974 through 1986, nocardial infection was diagnosed in 14 cancer patients treated at the M. D. Anderson Cancer Center (Houston). Underlying diseases included solid tumors in eight patients and hematologic malignancies in five; there was no underlying disease in one patient. The types of infection were bronchopneumonia, cavitary pneumonia, empyema, brain abscess, meningitis, and cutaneous abscesses. Eleven patients received antineoplastic therapy prior to the onset of their infection. Among the 11 patients in whom infection was diagnosed antemortem, nine who were treated with sulfadiazine or trimethoprim-sulfamethoxazole had a favorable response to therapy. Nocardiosis occurs infrequently in cancer patients but causes serious infection. Physicians must be alert to this possibility so that appropriate therapy can be given promptly and the chances of a favorable outcome thereby increased.

In vitro susceptibilities of Nocardia species to newer antimicrobial agents.

The in vitro activities of various quinolones, two newer cephalosporins, and imipenem against 23 strains of Nocardia asteroides, 4 strains of Nocardia brasiliensis, and 4 strains of Nocardia caviae were determined by an agar dilution method. PD-117558, a newer carboxyquinolone, and imipenem were the most active agents tested, inhibiting 90% of N. asteroides isolates at an MIC of 2 micrograms/ml. Of the 23 strains of N. asteroides, 15 were susceptible to cefpirome and 10 were susceptible to ciprofloxacin. The N. brasiliensis and N. caviae strains were very susceptible to PD-117558 (MIC, less than or equal to 1 microgram/ml), moderately susceptible to ciprofloxacin, and resistant to most of the other tested drugs.

Folate and pterin metabolism by cancer cells in culture.

Malignant cells grown in culture excrete into their growth medium a folate catabolite that can be seen as a blue-fluorescent region on paper chromatograms of such media. This folate catabolite has now been identified by paper chromatography, thin-layer chromatography, and combined gas chromatography-mass spectrometry as 6- hydroxymethylpterin and not as pterin-6-carboxaldehyde as previously reported. Moreover, when pterin-6-carboxaldehyde was added to the growth medium of logarithmically growing malignant cells, it was primarily reduced to 6-hydroxymethylpterin. In contrast pterin-6-carboxylate was the principal product formed from added pterin-6-carboxaldehyde by normal established cell lines in culture. These results have been interpreted as indicative of a possible mechanism of folate catabolism in malignant cells. Folic acid or another folate derivative is oxidatively cleaved at the C-9-N-10 bond to yield pterin-6-carboxaldehyde as one of the products. This derivative is subsequently reduced to 6-hydroxymethylpterin, which is excreted into the growth medium.