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Biomedical subjects

D Cotton

Publications and source records attributed to D Cotton.

49 records · Page 3Linked to original sources

A randomized trial of open lung biopsy versus empiric antimicrobial therapy in cancer patients with diffuse pulmonary infiltrates.

Twenty-four cancer patients with diffuse interstitial pneumonitis (DIP) were randomized to undergo an open lung biopsy (OLB) within 8 hours of presentation (12 patients) or to receive empiric antimicrobial therapy (ET) with trimethoprim-sulfamethoxazole (TMP-SMX) erythromycin for a minimum of 4 days (12 patients). Patients whose condition deteriorated underwent an OLB on day 4. Eight of 12 patients (67%) having OLB survived versus 10 of 12 (83%) receiving ET (P = .64). Morbidity occurred in nine of 12 (75%) having OLB versus eight of 12 (67%) receiving ET (P = 1.0). Concurrently, there were 14 additional cancer patients with DIP who were not randomized (nine refused, three had a coagulopathy contraindicating surgery, two were excluded by primary care physicians) and who were comparable demographically to the randomized group. Two received OLB and 12 ET. Combining the randomized and nonrandomized groups, eight of 14 (57%) having an initial OLB survived versus 18 of 24 (75%) of ET-treated patients (P2 = .19). Results of the OLB were seven Pneumocystis carinii pneumonia (PCP), five nonspecific pneumonitis (NSP), one cytomegalovirus, and one lymphoma. Results of OLB led to discontinuation of antibiotics in three patients. Of the 24 ET patients, eight failed to improve by day 4 and had an OLB. Results were two NSP, two PCP, two cancer, one blastomycosis, and one Candida pneumonia. Complications were seen in 10 of 14 (72%) initial OLB patients versus 14 of 24 (58%) patients on the ET arm (P = .65). When the complication rate between patients receiving only empiric antibiotics was compared with all patients having an OLB (initially or on day 4), the difference was greater in patients undergoing OLB (37% v 72%, respectively) (P2 = .14). ET with TMP-SMX plus erythromycin and broad spectrum antibiotics in granulocytopenic patients appeared to be as successful and potentially less toxic than an OLB in this study. Although the number of patients in this study was small, these data suggest that a trial of empiric antibiotic management may be reasonable in cancer patients presenting with DIP, especially if they are nonneutropenic.

Adult↗

A randomized trial comparing ceftazidime alone with combination antibiotic therapy in cancer patients with fever and neutropenia.

To assess the efficacy of single-agent therapy relative to standard combination antibiotic therapy for the initial management of fever and neutropenia in cancer patients, we conducted a randomized trial comparing ceftazidime alone with a combination of cephalothin, gentamicin, and carbenicillin. Of 550 evaluable episodes of fever and neutropenia, 282 were treated with ceftazidime alone and 268 with the combination. All episodes were evaluated for responses at 72 hours after the start of treatment and at resolution of the neutropenia. Of the patients with unexplained fever who were given ceftazidime alone, 99 percent were alive at 72 hours and 98 percent were alive when the neutropenia resolved, as compared with 100 percent and 98 percent, respectively, of those given combination therapy. Of the patients with documented infection who were given ceftazidime alone, 98 percent were alive at 72 hours and 89 percent when the neutropenia resolved, as compared with 98 percent and 91 percent, respectively, of those given combination therapy. The majority of episodes of documented infection in both treatment groups necessitated additional antimicrobial treatment or other modifications of the initial regimen, as compared with only 22 percent of the episodes of unexplained fever. We conclude that initial single-agent therapy with certain beta-lactam antibiotics is a safe alternative to standard combination antibiotic therapy, although patients with documented infection or protracted neutropenia are likely to require additional or modified treatment.

Adolescent↗

New beta-lactam antibiotics in granulocytopenic patients. New options and new questions.

Infectious complications are a frequent cause of morbidity and, at many centers, the major cause of death in patients with cancer. The increased risk and severity of infectious sequelae result from profound alterations in normal host defenses that occur secondary to the underlying malignancy and the treatment thereof. During the last decade, early empiric antibiotic therapy has become standard practice in the initial management of febrile granulocytopenic patients and has contributed significantly to the improved outcome among patients undergoing cancer therapy. Although early death due to unsuspected or inadequately treated bacterial infection has been largely overcome, new problems--also with life-threatening implications--have emerged. As the use of cancer chemotherapy continues to increase, new populations of patients are being placed at increased risk of infection. Defining the host and environmental factors that contribute to this risk assumes central importance for delineating those patients who require the most intense surveillance. Changing medical practices (e.g., increased use of indwelling catheters) have contributed to the emergence of new pathogens. Recent drug developments (e.g., the third-generation cephalosporins and extended-spectrum penicillins) offer new treatment options, as well as generate controversy and confusion. For example, authorities disagree on the optimal duration and modifications in treatment that are required by cancer patients who remain granulocytopenic and who thus are at continued risk of multiple infectious episodes or superinfections. A question of current interest is whether combination therapy with synergistic agents is important in light of the development of the third-generation cephalosporins and extended-spectrum penicillins. Several of these new antibiotics have an exceedingly broad spectrum of activity that includes Pseudomonas aeruginosa, as well as Enterobacteriaceae, Serratia, Citrobacter, indole-positive Proteus, and anaerobes (including Bacteroides fragilis). However, the third-generation cephalosporins are not as active against staphylococci and streptococci as are the first-generation cephalosporins, and none is effective against enterococci. Nonetheless, these agents achieve serum levels that can be 10 to 100 times greater than the minimal inhibitory and bactericidal concentrations of gram-negative bacteria, raising the possibility that these drugs might be effective as single agents. The advantages of the third-generation cephalosporins are their minimal toxicity and long serum half-lives.(ABSTRACT TRUNCATED AT 400 WORDS)

Agranulocytosis↗

Peripartum colloid osmotic pressure changes: effects of controlled fluid management.

A prospective, fluid-controlled study of serially measured colloid osmotic pressure changes in the peripartum period was undertaken. Seventeen patients with uncomplicated pregnancies undergoing elective cesarean section at term were administered a predelivery bolus of 15 ml/kg of lactated Ringer's solution prior to operation. Maintenance crystalloid fluids were infused at 125 to 150 ml/hr both intraoperatively and post partum without the addition of blood or other colloid solutions. Serial colloid osmotic pressure measurements were obtained before hydration, after hydration, after delivery, and at 6 and 24 hours post partum. The results demonstrated a 15.9% decline in colloid osmotic pressure immediately following the hydration bolus (20.7 +/- 1.5 to 17.4 +/- 1.8 mm Hg) (p less than 0.01). A further decline in colloid osmotic pressure to 16.6 +/- 1.7 mm Hg occurred after delivery and represented an overall 22% decrease from the baseline value (p less than 0.05). The lowest mean colloid osmotic pressure value occurred at 6 hours post partum (16.1 +/- 1.1 mm Hg). These data support previous observations that colloid osmotic pressure is uniformly lowered in the immediate postpartum period with peak reductions identified at 6 hours following delivery. In addition, intravenous crystalloid administration during the peripartum interval can substantially influence this decline in colloid osmotic pressure. Although no clinical evidence of cardiopulmonary compromise was observed in this set of normal gravid women, these data may be useful in the management of the parturient patient with established risk factors for pulmonary edema where alterations in the pulmonary capillary wedge pressure-colloid osmotic pressure gradient have been shown to correlate with the development of this complication.

Cesarean Section↗

Prospective randomized study of open lung biopsy versus empirical antibiotic therapy for acute pneumonitis in nonneutropenic cancer patients.

Diffuse pulmonary infiltrates and acute respiratory compromise frequently occur in patients with cancer who are undergoing chemotherapy, and treatment remains controversial. We initiated a prospective randomized trial in 22 nonneutropenic patients to compare the efficacy of immediate open lung biopsy with that of empirical trimethoprim-sulfamethoxazole and erythromycin therapy with delayed open lung biopsy if no clinical improvement occurred after 4 days of therapy. Diagnoses included non-Hodgkin's lymphoma (15 patients), T-cell lymphoma (2), acute lymphoblastic leukemia (3), Hodgkin's disease (1), and breast cancer (1). The median age was 40 years, and fever (18) and tachypnea (13) were the most frequent signs. Median room air arterial oxygen tension in 18 hypoxic patients was 53 mm Hg; 19 patients had diffuse pulmonary infiltrates. Eight of the 10 patients randomized to empirical antibiotic therapy showed improvement after 4 days. The 2 patients whose condition did not improve and who underwent delayed open lung biopsy had Pneumocystis carinii pneumonia. One of them did show improvement, and the other died of respiratory failure. Time to clinical resolution in the 9 surviving patients was 14 days; 4 required prolonged ventilation (longer than 24 hours). Findings for the 12 patients randomized to immediate open lung biopsy were P. carinii pneumonia in 7 and nonspecific pneumonitis in 5; there were 3 deaths related to open lung biopsy. Time to resolution in the surviving patients was 13 days for those with P. carinii pneumonia and 5 days for those with nonspecific pneumonitis; 7 required prolonged ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Comparative pharmacokinetics of cefoxitin in postpartum normotensive and pregnancy-induced hypertensive patients.

Limited pharmacokinetic data exist on cefoxitin, a semisynthetic cephamycin antibiotic, in the obstetric patient. Thirteen normotensive and five subjects with severe pregnancy-induced hypertension were identified within the first two postpartum days after cesarean section. After a 2 gm intravenous infusion, serial samples of blood were obtained and analyzed for cefoxitin by high-pressure liquid chromatography. Peak cefoxitin concentrations after infusion were 53.3 +/- 18.6 and 50.8 +/- 25.2 micrograms/ml for the normotensive and pregnancy-induced hypertensive groups, respectively. The only significant difference in pharmacokinetic parameters between these groups was a higher serum trough concentration of cefoxitin in the patients with pregnancy-induced hypertension as compared to the normotensive group. Because of diminished trough levels in our study patients, attention may need to be given to the adjustment of dosages in postpartum women with serious infections.

Adult↗

Approaching the controversies in antibacterial management of cancer patients.

The principles for management of infectious complications in cancer patients are continuing to evolve. The critical element includes the prompt institution of broad-spectrum antibiotic(s) empirically when granulocytopenic patients become febrile and continuation and modification of the regimen in patients with persistent fever and granulocytopenia. The view is presented that antibiotics provide systemic prophylaxis as well as therapy in persistently granulocytopenic patients and that they should be continued until all signs of infection have cleared or the granulocyte count has recovered. Such aggressive therapy, supplemented by continued evaluation and monitoring of the patient, can significantly reduce infection-relation morbidity and mortality.

Agranulocytosis↗

Anorectal infections in patients with malignant diseases.

Fifty-seven episodes of anorectal infection in 44 patients with malignant diseases primarily leukemia or lymphoma, have been retrospectively reviewed. Seventeen patients died in hospital, but only in seven cases was the anorectal infection a major contributing cause of death. The most important prognostic indicator of outcome was number of days of neutropenia during the infectious episode. Cultures obtained at the time of surgical drainage or by needle aspiration of the wound revealed multiple organisms in 26 of 29 instances, and anaerobic organisms were the commonest isolates. Anorectal infection was controlled in 28 (55%) of 51 treatment courses when antibiotics were the only treatment given. However, if the antibiotic regimen included both an aminoglycoside and an antibiotic with anaerobic coverage, control of infection was observed in 15 (88%) of 17 cases. There were 26 surgical procedures performed, with acceptable morbidity. Infection was controlled in 19 (73%) of 26 cases treated with surgery and antibiotics. The results support managing most of these infections initially with medical treatment, using an antibiotic regimen that includes an aminoglycoside and a specific drug against anaerobes. Surgery is recommended if there is obvious fluctuance, a significant amount of necrotic tissue evident, or progression of the infection locally or continued sepsis after an adequate antibiotic trial.

Adolescent↗