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Biomedical subjects

S C Schimpff

Publications and source records attributed to S C Schimpff.

At least 55 records · Page 3Linked to original sources
PubMed1985

Potential of imipenem as single-agent empiric antibiotic therapy of febrile neutropenic patients with cancer.

Infection remains a major cause of morbidity and mortality for the patient with cancer who experiences episodes of severe granulocytopenia. The search continues for new antimicrobial agents with improved efficacy and lower incidence of toxicity. Imipenem is a new carbapenem antibiotic which possesses a broad antibacterial spectrum with excellent activity against Pseudomonas aeruginosa and the other commonly recovered enteric gram-negative bacilli that infect the granulocytopenic patient with cancer. The combination of imipenem plus an aminoglycoside has shown in vitro synergy against P. aeruginosa and Staphylococcus aureus whereas the combination of imipenem plus piperacillin or the extended spectrum cephalosporins have frequently shown antagonism when tested against P. aeruginosa and Serratia marcescens. The use of a P. aeruginosa-infected neutropenic rat model has provided an in vivo system to evaluate the activity of new antibiotics or antibiotic combinations. Monotherapy with imipenem is as effective in this model as any of the currently available synergistic antibiotic combinations. This degree of activity has not been found with other broad-spectrum antibiotics when used alone. Imipenem provides serum bactericidal activity well above a 1:8 dilution for the four most commonly isolated pathogens: P. aeruginosa, Escherichia coli, Klebsiella species, and S. aureus. In addition, imipenem's post-antibiotic effect against P. aeruginosa may be pertinent. Imipenem is a unique antibiotic, with properties that make it well suited for study as monotherapy for fever and suspected infection in granulocytopenic patients with cancer. A prospective randomized, double-blind study comparing imipenem with a control regimen of piperacillin plus amikacin as empiric antibiotic therapy of febrile granulocytopenic patients with cancer is currently underway at the University of Maryland Cancer Center.

Agranulocytosis↗
PubMed1985

Safety and tolerability of multiple doses of imipenem/cilastatin.

The safety and tolerability of 1 gm imipenem and cilastatin given together every 6 hours for 10 days was evaluated in a randomized, double-blind, placebo-controlled trial in normal subjects. Nausea was more common in the drug-treated group (five of six subjects) than in the control group (two of six subjects). No consistent changes in hepatic function indices were noted. Although beta 2-microglobulin excretion showed a significant trend of rising over time in the drug group, there were no differences between groups with regard to 24-hour urinary excretion of either N-acetyl-beta-glucosaminidase or beta 2-microglobulin. Urinalysis did not reveal any casts and serial creatinine clearance determinations showed no change in renal function in either the drug- or placebo-treated groups. Pure tone audiograms were performed before and after dosing in 11 of 12 subjects; no changes were noted. We conclude that the combination of imipenem and cilastatin was well tolerated and safe.

Acetylglucosaminidase↗
PubMed1985

Comparative pharmacokinetics and serum bactericidal activity of mezlocillin, ticarcillin and piperacillin, with and without gentamicin.

We compared the serum levels, pharmacokinetics and serum bactericidal activity after intravenous infusions of 5 g of each of three anti-pseudomonal penicillins--ticarcillin, mezlocillin and piperacillin alone and in combination with 80 mg gentamicin in normal volunteers. Gentamicin levels were significantly lower when administered with ticarcillin than when administered with mezlocillin or piperacillin. Serum levels of ticarcillin and piperacillin immediately after the infusion were similar (approximately 450 mg/l) and were higher than mezlocillin at 350 mg/l, but by 6 h, levels of all three penicillins were less than 10 mg/l. Overall, the geometric mean bactericidal titres produced in the serum against organisms which commonly infect cancer patients with granulocytopenia were highest with the piperacillin-gentamicin combination. However, except for the mezlocillin-gentamicin combination against Pseudomonas aeruginosa, serum bactericidal titres of all three penicillin-gentamicin regimes were greater than 1:8 at zero and 2 h after the infusion against the organisms tested. It is unlikely that these differences in the three penicillin-gentamicin combinations will be apparent in the outcome of clinical trials for empiric therapy of fever in the cancer patient with granulocytopenia.

Adult↗
PubMed1985

Autopsy findings after prolonged catheterization of the right atrium for chemotherapy in acute leukemia.

Autopsies performed upon 59 patients treated for acute leukemia through venous access provided by long term right atrial catheters demonstrated a significant incidence of thrombus formation in the vena cava or right atrium. Similar thrombi were not present in 49 patients who were treated for the same disease without long term catheters. The clinical significance of these lesions, which were not usually seen with less than 150 days of catheter use, is unclear. No increase in the likelihood of other pathologic lesions, specifically of pulmonary emboli, was seen to accompany thrombus formation nor did they seem in any way contributory to the demise of the patient. No good screening test is yet available to detect these lesions ante mortem.

Adolescent↗
PubMed1984

The plasma pharmacokinetics of high dose (1 g) imipenem coadministered with 1 g cilastatin in six normal volunteers.

The plasma pharmacokinetics of imipenem, a beta-lactam antibiotic of the new class of carbapenems, was evaluated by administering 1 g imipenem plus 1 g of the dehydropeptidase inhibitor cilastatin to six healthy male volunteers over 30 min. Subsequently intensive plasma sampling was done for 5.5 h. The volume of distribution of the central compartment was 0.16 +/- 0.04 1/kg; the volume of distribution (area) was 0.28 +/- 0.07 1/kg; the volume of distribution (steady state) was 0.23 +/- 0.03 1/kg. The mean plasma clearance was 10.1 +/- 1.0 1/h/1.73 m2. Model-independent analysis showed excellent agreement with these values. The terminal excretion half-life was short (1.3 +/- 0.4 h). For approximately 6 h after administration, the observed plasma levels were above those required to inhibit most nosocomial pathogens in vitro.

Adolescent↗
PubMed1984

Can antibacterial therapy be discontinued in persistently febrile granulocytopenic cancer patients?

It has been suggested that empiric broad-spectrum antibiotics, instituted for fever in the presence of granulocytopenia, should continue to be administered, even when infection is not demonstrable, to those patients who remain persistently febrile and granulocytopenic. Therefore, the consequences of discontinuing antibiotics when the presence of infection is doubted in this setting were evaluated. In 16 (3.7 percent) of 429 episodes of fever and granulocytopenia for which empiric antibiotic therapy was instituted, after approximately four days, persistence of both fever and granulocytopenia was found, and yet infection was prospectively classified at that time as "doubtful." The initial empiric antibiotic regimen was therefore discontinued after a mean of 4.8 (median 5.0) days. Discontinuation of antibiotics proved appropriate for half of the patients; eight patients received no systemic therapeutic antibiotics with no evidence of infection during a period of at least two weeks. The other eight patients had antibacterial antibiotics reinstituted within a mean of 2.4 days; six infections were subsequently demonstrable. Six of these eight patients also required or were believed to require antifungal therapy with intravenous amphotericin B for presumed fungal infections. Patients with relapsed leukemia or lymphoma and those with a likelihood of continued profound granulocytopenia (counts below 100/microliters) or both were the ones who tended to require reinstitution of antibiotics. Discontinuation of antibiotics when infection was considered doubtful despite persistence of both fever and granulocytopenia was, therefore, successful in eight of 16 patients. Reinstitution of antibiotics was required in the eight remaining patients. No definite rule appears to be applicable to all patients.

Agranulocytosis↗
PubMed1984

Persistent isolation of an unusual Pseudomonas species from a phenolic disinfectant system.

A well-characterized unusual Pseudomonas species contaminated the piped disinfectant system of a newly-opened laminar air flow intensive care facility. This organism was frequently isolated (10(4)-10(6) cfu/ml) from phenolic diluted 1:256 in the system, and could also be recovered (0.01-0.2 cfu/ml) from undiluted phenolic. During the 20-month period when this unusual Pseudomonas was present, none of the severely compromised, granulocytopenic oncology patients treated in the intensive care facility were either colonized or infected with this Pseudomonas sp. Eradication of the organism from the system proved difficult and was accomplished by removing a contaminated reservoir of diluted phenolic disinfectant followed by transient cleansing of the system with very high concentrations (84,000 ppm) of chlorine. This experience demonstrates that phenolics should be added to the list of disinfectants which can harbor Pseudomonas spp. in the clinical setting.

Air Microbiology↗
PubMed1984

Effect of Hickman catheters on the self-esteem of patients with leukemia.

Hickman right atrial catheters are useful in providing prolonged access for chemotherapy. Their presence does alter body image, however, and the maintenance of catheter patency during periods of outpatient care demands patient cooperation and participation. To determine whether the alterations in body image and life-style brought about by catheter insertion would have a negative effect upon the self-esteem of patients with acute leukemia, "purpose-in-life" testing was done prospectively in two groups of patients treated over a 30-day period with and without right atrial catheters. No significant alterations in self-esteem were noted during the study period in response to the use of Hickman catheters. The results suggest that Hickman catheters can be used as needed to improve venous access in patients with acute leukemia, without fear that this will adversely affect self-esteem.

Adult↗
PubMed1984

Bactericidal activity of ceftazidime in serum compared with that of ticarcillin combined with amikacin.

We compared the bactericidal activity of serum attained 1 and 6 h after the termination of infusions of either ceftazidime (2 g) or ticarcillin plus amikacin (5 g and 7.5 mg/kg, respectively) in 6 volunteers against a panel of the most common pathogens found in the blood of febrile granulocytopenic cancer patients. Ceftazidime consistently produced significantly higher serum bactericidal titers at both 1 and 6 h against all species of gram-negative bacilli. Its performance against Pseudomonas aeruginosa was especially impressive. The geometric mean titer against this organism was 1:41 at 1 h, contrasted with 1:12 for ticarcillin plus amikacin (P = 0.025). However, for Staphylococcus aureus, the geometric mean serum bactericidal titer of ceftazidime was 1:3.6 at 1 h and undetectable at 6 h. Ceftazidime shows promise as single-agent therapy for serious gram-negative bacillary infections. Whether this promise is fulfilled and whether the observed antistaphylococcal activity is adequate for empiric therapy in infected granulocytopenic patients need further investigation.

Adolescent↗
PubMed1984

Comparison of the pharmacokinetics of ceftazidime and moxalactam and their microbiological correlates in volunteers.

We compared ceftazidime with moxalactam, a commonly utilized, currently available drug. The microbiological activities of ceftazidime and moxalactam were studied. In addition, single-dose pharmacokinetics and serum bactericidal activity 1 and 6 h after a 2.0-g, 30-min infusion of each drug were determined in a crossover study in human volunteers. In vitro, both drugs had MICs for 90% of the isolates of less than 1.0 microgram/ml against the common members of the family Enterobacteriaceae and of 8.0 micrograms/ml against Staphylococcus aureus. Against Pseudomonas aeruginosa ceftazidime was more active than moxalactam, the respective MICs for 90% of the isolates being 8 and 128 micrograms/ml. Mean half-lives were 1.75 (+/- 0.21) h for ceftazidime and 2.5 (+/- 0.38) h for moxalactam. The serum bactericidal titers for both compounds against Escherichia coli and Klebsiella pneumoniae were high. Titers against S. aureus 6 h after infusion were negative. The mean (geometric) serum bactericidal titer of ceftazidime against 31 strains of P. aeruginosa (1:44) was higher than that of moxalactam (1:3.4).

Adolescent↗
PubMed1984

Multiple-dose pharmacokinetics of imipenem-cilastatin.

We characterized the pharmacokinetic profile of imipenem-cilastatin administered intravenously to six normal volunteers in a dose of 1,000 mg of each drug every 6 h for 40 doses. The plasma concentrations of imipenem and cilastatin 1 h after the end of a 30-min infusion were 18.7 (+/- 2.1) and 19.1 (+/- 4.6), 20.0 (+/- 3.2) and 17.8 (+/- 4.8), and 23.4 (+/- 2.3) and 19.1 (+/- 3.5) micrograms/ml in the 1st, 17th, and 37th dosing intervals, respectively. The central compartment volumes of distribution for imipenem and cilastatin were 0.16 (+/- 0.05) and 0.14 (+/- 0.03) liter/kg, respectively. Elimination half-lives were short: 0.93 (+/- 0.09) h for imipenem and 0.84 (+/- 0.11) h for cilastatin. Plasma clearances were 12.1 (+/- 0.06) liters/h per 1.73 m2 for imipenem and 12.4 (+/- 1.1) liters/h per 1.73 m2 for cilastatin. Renal clearance accounted for 54% of the plasma clearance of imipenem and 69% of the plasma clearance of cilastatin. The concentrations of imipenem in plasma and urine remained above the MICs of the vast majority of pathogens throughout the dosing interval.

Adult↗
PubMed1983

Prolonged venous access for chemotherapy by means of the Hickman catheter.

One hundred and six long-term right atrial (Hickman) catheters have been used to establish permanent venous access in 99 patients undergoing prolonged chemotherapy for leukemia and other malignancies at the University of Maryland/Baltimore Cancer Research Center over the 30-month period from November 1978 to May 1981. A uniform technique for insertion, using cannulation of the external or internal jugular vein and atraumatic dissection of the subcutaneous tunnel, has resulted in no episodes of hemorrhage or tunnel infection in the last 55 placements in these high-risk granulocytopenic, thrombocytopenic patients. Twelve catheters have now been in place for over one year, and two catheters have been in place for over two years without apparent ill effects. A low catheter related infection rate is attributed to meticulous adherence to catheter care guidelines, supervised by a single trained and interested nurse.

Adolescent↗
PubMed1983

Evaluation of levamisole as an adjuvant to chemotherapy for treatment of ANLL.

Levamisole is a synthetic, orally administered, relatively nontoxic compound with immunorestorative ability. Levamisole was tested in this study of 60 adults with acute nonlymphocytic leukemia (ANLL) to determine if augmentation of response rate or duration, or survival over that obtained with a standard chemotherapy regimen alone would result. The chemotherapy regimens for all patients consisted of daunorubicin and cytosine arabinoside for induction and consolidation, methotrexate with citrovorum factor reversal in a cytoreductive phase, and late intensification with thioguanine and cytosine arabinoside. The first 30 patients received chemotherapy alone; a second group of 30 patients were scheduled to receive levamisole in addition to chemotherapy. Levamisole, 45 mg/m2, was administered orally twice daily for three consecutive days each week beginning one week after the initiation of induction chemotherapy and continuing until relapse. No significant difference emerged between the two groups with respect to remission rate, time to achieve remission, postrelapse survival, or total survival. However, a trend towards improved postcomplete remission survival (P = 0.072) was noted in the levamisole group, and patients who received levamisole had a significantly greater reinduction rate after relapse (P = 0.019).

Adult↗
PubMed1983

Hepatitis in patients with acute nonlymphocytic leukemia.

Three consecutive groups (University of Maryland Cancer Center protocols 7110, 7405, and 7802) of patients with acute nonlymphocytic leukemia who achieved a complete hematologic remission with similar antileukemic therapy were reviewed for the development of hepatitis. Ninety-four (73 percent) experienced viral hepatitis; eight had type B hepatitis and 86 had non-A/non-B hepatitis. The hepatitis was mild in all patients. Hepatitis secondary to cytomegalovirus, herpes simplex virus, Epstein-Barr virus, or Toxoplasma gondii was not observed. Antibody to type A hepatitis was common, but acute infection could not be substantiated. All cases of type B hepatitis in which the surface antigen could be serotyped were found to have the less frequently observed ayw marker, suggesting a common donor as the source of infection. The median duration of complete remission was longer (p = 0.03) for patients in Group II (protocol 7405) who contracted hepatitis (247 days) compared with patients without hepatitis (125 days). Median overall survival was also longer (p = 0.01) for these patients in whom hepatitis developed (672 days versus 372 days, respectively). No prolongation of complete remission duration or survival could be demonstrated for patients from Group I (protocol 7110) or Group III (protocol 7802) who contracted hepatitis. In patients with hepatitis, the height of transaminase serum bilirubin levels or duration of abnormal results of liver function tests did not correlate with the duration of complete remission or survival. Hepatitis, a common infection in those patients with acute nonlymphocytic leukemia who undergo induction therapy, had an inconsistent effect on the duration of complete remission interval and overall survival.

Acute Disease↗
PubMed1983

Infection among 210 patients with surgically staged Hodgkin's disease.

To determine the incidence and types of infections in Hodgkin's disease, particularly those related to the overwhelming pneumococcal sepsis syndrome, 210 consecutive patients with previously untreated Hodgkin's disease who underwent staging laparotomy with splenectomy from March 1968 to October 1979 were reviewed. For 178 patients (85 percent) alive at the end of the study, the mean follow-up time was 68.1 months. Eighty-two serious infections occurred among 59 (28 percent) of the patients; 47 (57 percent) serious infections were microbiologically documented and 35 (43 percent) were clinically documented. Forty-seven microbiologically documented serious infections occurred in 34 patients and consisted of 23 episodes of pneumonia, 10 cases of bacteremia, seven wound infections, two cases of disseminated herpes zoster, one subphrenic abscess, and four miscellaneous infections. Microbiologically documented serious infections occurring during initial treatment or remission had lower incidences of leukopenia (29 versus 58 percent) (p = 0.09) and death (11 versus 53 percent) (p = 0.005) than those occurring after relapse of Hodgkin's disease. Of the microbiologically documented serious infections, 76 percent were associated with a predisposing factor(s) (leukopenia, postoperative state, steroids, peripheral neuropathy, leukemia), of which 34 percent were fatal. Microbiologically documented serious infections unassociated with a predisposing factor were never fatal, including the only episode of pneumococcal sepsis in the series. In contrast to microbiologically documented serious infections, only 14 percent of clinically documented serious infections (versus 38 percent) were fatal. The overwhelming pneumococcal sepsis syndrome and other infections thought to be associated with the asplenic state are uncommon problems in patients with Hodgkin's disease after splenectomy.

Adolescent↗
PubMed1983

Prevention of infection among patients with cancer.

Recognition of the alterations of host defense allows a rational approach to preventing associated infections. One of the most effective strategies for preventing infection in the granulocytopenic patient is the combined use of oral non-absorbable antibiotics, laminar air-flow room reverse isolation with strict housekeeping techniques, low microbial diet, sterile water, and topical antiseptics and antibiotics. The prohibitive cost, however, warrants that this system be restricted to research settings. The suppression of aerobic Gram-negative bacilli and fungi and the preservation of colonization resistance with such combinations as trimethoprim-sulfamethoxazole and nystatin show promise in preventing infection in the granulocytopenic patient. Prevention of infection in neutropenic patients also requires attention to simpler but very effective measures such as immunizations, antimicrobial prophylaxis against intracellular and nonbacterial pathogens in high-risk patients, limiting invasive diagnostic and monitoring procedures, hand-washing by all personnel between visiting patients, oral hygiene, low microbial diets, axillary and perianal swabbing, and care with venipunctures and marrow aspirates. Finally, while the recommendations for prevention of infection are likely to continue to change with resulting improvement in patient care [92, 93], a tabulation summarizing current practices can be established based on our current knowledge (Table 1).

Agranulocytosis↗
PubMed1983

Selective antimicrobial modulation as prophylaxis against infection during granulocytopenia: trimethoprim-sulfamethoxazole vs. nalidixic acid.

Sixty-two profoundly granulocytopenic patients with acute leukemia undergoing induction chemotherapy were prospectively randomized to receive either trimethoprim-sulfamethoxazole plus nystatin or nalidixic acid plus nystatin for prevention of infection. Patients given trimethoprim-sulfamethoxazole plus nystatin during initial remission induction experienced an increased duration (22.6 vs. 13.6 days) of profound granulocytopenia (less than 100 granulocytes/mm3; P = 0.007). Acquisition of gram-negative bacilli was more frequent among patients treated with nalidixic acid plus nystatin while filamentous fungi were acquired more frequently by patients receiving trimethoprim-sulfamethoxazole plus nystatin (P = 0.05). The median duration of on-study time prior to documentation of first infection was longer for patients receiving trimethoprim-sulfamethoxazole plus nystatin (17 days) than for those receiving nalidixic acid plus nystatin (eight days) (P = 0.0002). Three infection-related deaths occurred among patients receiving nalidixic acid; seven occurred among patients receiving trimethoprim-sulfamethoxazole, five of which were secondary to pneumonia due to Aspergillus flavus. Both of these methods of selective antimicrobial modulation have apparent advantages, but each has disadvantages serious enough to limit their routine use.

Adolescent↗