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Biomedical subjects

S C Schimpff

Publications and source records attributed to S C Schimpff.

At least 73 records · Page 4Linked to original sources
PubMed1983

Imipenem therapy of Pseudomonas aeruginosa bacteraemia in neutropenic rats.

Rats were made neutropenic by intraperitoneal (ip) injection of cyclophosphamide. Those neutropenic (mean white blood cell count of 470/mm3) rats were challenged intraperitoneally with Pseudomonas aeruginosa to assess the efficacy of single agent therapy with either imipenem, latamoxef (moxalactam) or amikacin, or combination therapy with imipenem-amikacin or latamoxef (moxalactam)--amikacin. Pharmacokinetic studies were performed in rats to assure that therapy was equivalent during therapeutic trials. Three levels of bacterial challenge (4 LD50, 13 LD50 and 250 LD50) were examined. At all challenge levels, single agent therapy with latamoxef (moxalactam) failed to significantly protect rats from fatal bacteraemia. Single-agent therapy with amikacin did significantly protect rats from fatal bacteraemia at the lower challenge levels, but not at the 250 LD50 challenge. Single agent therapy with imipenem significantly protected rats at all challenge. Single agent therapy with imipenem significantly protected rats at all challenge levels. In-vitro studies established a synergistic effect when combination antibiotics were used. This correlated with in-vivo findings that combination therapy resulted in improved rat survival and recovery of fewer Ps. aeruginosa isolates. The latamoxef (moxalactam)-amikacin combination was more effective than either agent alone, but was not more effective than imipenem alone. The imipenem-amikacin combination was the most effective therapeutic regimen tested. These results suggest that imipenem alone, and particularly when combined with an aminoglycoside, is effective in treating serious Ps. aeruginosa infections in neutropenic rats. Clinical studies in infected immunocompromised patients may be warranted.

Agranulocytosis↗
PubMed1983

Trimethoprim/sulfamethoxazole versus placebo: a double-blind comparison of infection prophylaxis in patients with small cell carcinoma of the lung.

The suppression of pathogenic aerobes and the preservation of anaerobes provides a degree of infection prevention during granulocytopenia. Trimethoprim/sulfamethoxazole (TMP/SMZ) suppresses Enterobacteriaceae and probably maintains colonization resistance through sparing of anaerobes. TMP/SMZ (320/1600 mg/day) treatment was compared to placebo in a double-blind, randomized trial in patients with newly diagnosed small cell carcinoma of the lung during the initial courses of chemotherapy with cyclophosphamide, doxorubicin, and etoposide. Infections were evaluated as microbiologically documented, with or without bacteremia, and clinically documented and were correlated to granulocytopenia. Of the 61 patients evaluated, 32 were given TMP/SMZ and 29 were given placebo; both groups had similar characteristics with regard to disease extent, performance status, age, sex, chemotherapy, and days of granulocytopenia. Incidence of infection at less than 100 granulocytes/microliters was significantly reduced in the TMP/SMZ group (2 infections/100 days) compared to placebo (11 infections/100 days, p = 0.005). Also reduced were the number of bacteremias and the mean proportion of study time on broad-spectrum antibiotics (p less than 0.01). Compared to placebo, TMP/SMZ provided infection prophylaxis without an increase in marrow suppression among patients with small cell carcinoma of the lung receiving intensive chemotherapy.

Adult↗
PubMed1983

Antibiotic combinations for the empiric treatment of the febrile neutropenic patient.

Empiric antimicrobial therapy in the granulocytopenic patient has traditionally consisted of a combination of an aminoglycoside plus a cephalosporin or aminoglycoside plus an antipseudomonal penicillin. These combinations have been proven reasonably effective and only moderately toxic. In some centers trimethoprim-sulfamethoxazole combined with an aminoglycoside or antipseudomonal penicillin has been used, again with good efficacy and minimal toxicity. The newer extended spectrum penicillins and cephalosporins has made possible two-drug combinations with aminoglycosides that provide double coverage of nearly all of the common bacterial pathogens while concurrently providing synergy against most of these same organisms. Further, it is now possible to have a double beta-lactam combination of a penicillin and cephalosporin which has the advantages of broad spectrum by both antimicrobials and, at times, synergistic activity but without the ototoxicity and nephrotoxicity of aminoglycosides. The double beta-lactam combination would be especially useful in the neutropenic patient with established renal insufficiency or a history of previous courses of aminoglycoside therapy. Care should be taken in choosing such a regimen, however, because some combinations demonstrate antagonism. There is increasing data to indicate that patients with profound (less than 100 microliters), persistent (greater than 14 days) granulocytopenia and concurrent gram-negative bacteremia respond best if treated with two active, bactericidal antibiotics, preferably synergistic in action. The potential for synergistic activity of the drugs selected should be, therefore, carefully considered. The duration of therapy should be adjusted according to the severity of infection, the response of the infection to antimicrobial therapy, and rate of recovery of the patient's granulocyte count.

Agranulocytosis↗
PubMed1983

Dual lumen catheters for angioaccess in patients with leukemia.

Dual lumen long-term indwelling right atrial catheters have been used to improve venous access in adult patients with leukemia. Twenty-eight such catheters have functioned for 1,895 days in 28 patients over the past eight months at the University of Maryland Hospital. Although insertion of the dual lumen catheter was more technically demanding than insertion of a single lumen catheter, the greater versatility in drug management (e.g., administration of two continuous infusions simultaneously or one continuous infusion leaving one line for platelets, blood, antibiotics or venous sampling) provided by the extra venous portal of entry more than compensated for any increased operative time (average, 58 vs 39 min/insertion). Eight episodes of bacteremia (0.37/100 patient days) occurred in these patients, but only one of these was associated with an exit site infection: the remainder were secondary to infections remote from the catheter. No catheter was removed as a result of these episodes, nor was any removed for ante mortem mechanical failure. The dual lumen catheter is a safe reliable device for providing angioaccess in patients with leukemia and offers substantially greater flexibility than the single lumen catheter.

Adult↗
PubMed1982

Long-term amikacin use. Effects on aminoglycoside susceptibility patterns of gram-negative bacilli.

Amikacin sulfate was first used sparingly at our cancer center in 1976; since 1979, it has been the only aminoglycoside used for systemic cancer therapy for patients with granulocytopenia. As the development of resistance has been correlated with antibiotic use over time, we wished to determine if prolonged use of amikacin in our patients had led to increased amikacin resistance. A total of 1,129 strains were recovered from 315 patients during a 13-month period. Each species isolated per patient was considered once. Seven percent of the patients had amikacin-resistant strains (2.7% of isolates), and 10% of patients had gentamicin-resistant strains (4% of isolates). Amikacin resistance was significantly less than in an earlier study. Unrestricted use of amikacin has not led to a concomitant increase in amikacin resistance in gram-negative bacilli.

Amikacin↗
PubMed1982

Empiric antibiotic therapy for suspected infection in granulocytopenic cancer patients: a comparison between the combination of moxalactam plus amikacin and ticarcillin plus amikacin.

Moxalactam is a new cephalosporin with a broad spectrum of activity which includes Pseudomonas aeruginosa in addition to Klebsiella species Escherichia coli, and Staphylococcus aureus. Moxalactam was combined with amikacin (M + A) compared to ticarcillin plus amikacin (T + A) in a prospective, randomized double-blind trial of empiric therapy for febrile episodes among granulocytopenic cancer patients. One hundred and ninety-one epidoses were evaluated; T + A, 93 episodes and M + A, 98 episodes. Median granulocyte count of initiation of therapy was less than 100/microliters. Overall response rates were good. In the T + A group, 21 of 29 (72 percent) microbiologically documented infections, including seven of 14 (50 percent) bacteremias, and 24 of 27 (89 percent) clinically documented infections improved. In the M + A group, 20 of 28 (71 percent) microbiologically documented infections, including 11 of 18 (61 percent) bacteremias, and 25 of 25 (96 percent) clinically documented infections resolved. Adverse effects were minimal and equivalent in both groups. Hypokalemia (decrease in serum potassium of greater than 11 mEq/liter from baseline) occurred in 14 of the 93 episodes in the T + A group and in 10 of the 98 episodes in the M + A group with decline in mean serum potassium level of 0.5 and 0.4 mEq/liter respectively. Nephrotoxicity (increase in serum creatinine greater than 0.04 mg/dl) occurred in only one patient in the T + A group and in two patients in the M + A group. Moxalactam plus amikacin has a broader in vitro spectrum, is as effective, and is no more toxic than ticarcillin plus amikacin as empiric therapy for febrile granulocytopenic cancer patients.

Adolescent↗
PubMed1982

Comparison of standard versus pharmacokinetically adjusted amikacin dosing in granulocytopenic cancer patients.

The capabilities of two pharmacokinetic amikacin dosing methods were evaluated and compared with the standard amikacin dosage recommended by the manufacturer. Study patients participated in two consecutive prospective randomized double-blind trials of empiric antibiotic therapy for febrile episodes during granulocytopenia. Patients in study 1 received amikacin at a dosage of 15 mg/kg per day in four divided doses in combination with either ticarcillin or piperacillin. Patients in study 2 received either ticarcillin or moxalactam in combination with amikacin. Amikacin dosages in study 2 were adjusted to achieve a 1-h-postinfusion concentration of approximately 25 micrograms/ml and a trough concentration of approximately 8 micrograms/ml. Initial amikacin dosage requirements were established based on the lean body weight and estimated renal function of the patient. If amikacin serum concentrations were not within acceptable ranges, further dosage adjustments were made by using patient-specific pharmacokinetic parameters. The median 1-h-postinfusion concentration of amikacin in study 1 was 13.0 micrograms/ml, with a median trough concentration of 6.1 micrograms/ml. In study 2 the median 1-h-postinfusion concentration was 20.8 micrograms/ml, with a median trough of 6.4 micrograms/ml. Patients in study 2 required a mean dosage of 29.4 mg/kg per day. The incidence of amikacin-induced nephrotoxicity was not increased despite the substantial increase in dosage. Ototoxicity was not evaluated in study 1, but the incidence of ototoxicity in study 2 (17%) exceeded the incidence observed in a previous amikacin-plus-ticarcillin trial in which patients received 15 mg of amikacin per kg per day.

Agranulocytosis↗
PubMed1982

A comparative evaluation of two fiberoptic bronchoscopy catheters: the plugged telescoping catheter versus the single sheathed nonplugged catheter.

We prospectively evaluated the ability of the plugged telescoping catheter (PTC) brush and the single sheathed nonplugged catheter brush to provide sterile lower respiratory tract samples during fiberoptic bronchoscopy in 19 noninfected patients with cancer. Both brushes were evaluated, in random order, in each of the 19 patients. The PTC brush and the single sheath brush were sterile in 12 and 5 patients, respectively, and in 7 patients, the PTC brush alone was sterile (p = 0.016, two-sided). Patients were anesthetized by lidocaine administered through the bronchoscope (6 patients), via an aerosol (3 patients), or by transtracheal injection (10 patients). The advantage of the PTC brush was evident only when aerosol or transtracheal anesthesia were used; the PTC brush was sterile in 9 of 13 patients, whereas the single sheathed brush was sterile in only 2 of these 13 (p = 0.016, two-sided). The plugged telescoping catheter brush is therefore more suitable than the single sheathed brush catheter for delivering sterile brushes to the lower respiratory tract during fiberoptic bronchoscopy.

Aerosols↗
PubMed1982

Staphylococcus epidermidis: an increasing cause of infection in patients with granulocytopenia.

Staphylococcus epidermidis, a major component of the skin flora, is usually considered a contaminant when recovered from diagnostic cultures. Since 1974 infections caused by gram-negative bacilli and S. aureus occurring among patients with granulocytopenic cancer have remained constant; infections due to S. epidermidis occurring before 1977 at a rate of 2.0 per 1000 days of hospitalization of patients with acute leukemia, increased to 14.6 per 1000 days in 1979. All S. epidermidis infections before 1977 originated from skin sites; since 1977 the respiratory tract and alimentary canal have become the predominant sites of origin. Predisposing factors for infection were profound granulocytopenia (less than 100/microL), a diagnosis of acute leukemia, and an oral nonabsorbable antibiotic regimen lacking vancomycin. The increased incidence of infection was not related to a nosocomial source or the more frequent use of long-term indwelling catheters. Methicillin resistance among isolates was common (40%). Intravenous vancomycin therapy provided the best therapeutic results. Diagnostic cultures positive for S. epidermidis in the setting of infection and profound granulocytopenia warrant appropriate antibiotic therapy.

Adult↗
PubMed1982

Periodontal infection in patients with acute nonlymphocyte leukemia. Prevalence of acute exacerbations.

From the initiation of chemotherapy until attainment of complete remission, 22 newly diagnosed, hospitalized patients with acute nonlymphocytic leukemia were studied for the prevalence of periodontal disease at admission and for acute exacerbations during myelosuppressive chemotherapy. Consistent with a normal population, all patients had asymptomatic periodontal disease at admission. In these 22 patients, 47 acute infections developed, including 13 of periodontal origin. All but three acute periodontal infections occurred during pronounced granulocytopenia (less than 100 granulocytes per microliter). Although signs and symptoms of inflammation were minimal, all 13 episodes were associated with pain and fever. Asymptomatic periodontal disease is readily overlooked but can be easily diagnosed by thorough clinical and roentgenographic examination. Its occurrence in patients with acute leukemia and its acute exacerbation during granulocytopenia indicate that this oral infection is associated with considerable morbidity during the treatment of acute nonlymphocytic leukemia.

Acute Disease↗
PubMed1981

Two methods for improved venous access in acute leukemia patients.

Arteriovenous fistulae and long-term indwelling right atrial (Hickman) catheters have been used as methods to improve venous access in patients with acute leukemia. The creation of 28 fistulae provided short duration of function (median, 12 days), with eight fistulae functioning less than 24 hours. Complications were negligible, and no increase in the incidence of bacteremia occurred. Fifty-one Hickman catheters have been placed, with a median placement granulocyte count of 335/microliters. The median duration of function has been 91 days or more, with 19 still functioning and 25 other catheters functioning at the time of the patient's death. Complications have been minimal, with substantial postoperative hemorrhage occurring primarily in patients with active disseminated intravascular coagulopathy at the time of catheter placement. Catheter-associated infections were uncommon. The overall incidence of bacteremia was not increased in patients with Hickman catheters, and 28 of the 30 bacteremias that occurred while catheters were in place (three catheter associated) resolved without catheter removal. The Hickman catheter is a safe, reliable device for improvement of venous access in adult patients with acute leukemia.

Acute Disease↗
PubMed1981

A comparison of trimethoprim-sulfamethoxazole plus nystatin with gentamicin plus nystatin in the prevention of infections in acute leukemia.

Fifty-three profoundly granulocytopenic patients with relapsed acute leukemia who were undergoing reinduction chemotherapy were prospectively randomized to receive either trimethoprim-sulfamethoxazole plus nystatin or gentamicin plus nystatin for prevention of infections. The acquisition of new organisms per patient during the total study period was similar in both groups. Thirty-five symptomatic infections (five of which were bacteremias) occurred in patients receiving trimethoprim-sulfamethoxazole plus nystatin, whereas 31 infections (eight bacteremias) occurred in patients receiving gentamicin plus nystatin. Four deaths related to infection occurred in patients taking trimethoprim-sulfamethoxazole, and eight occurred in patients taking gentamicin. We conclude that trimethoprim-sulfamethoxazole plus nystatin was approximately as effective as gentamicin plus nystatin for prophylaxis against infection in relapsed acute leukemia. Furthermore, side effects were fewer and compliance was better with trimethoprim-sulfamethoxazole plus nystatin.

Acute Disease↗
PubMed1981

Antibiotic combination-associated nephrotoxicity in granulocytopenic patients with cancer.

Antibiotic combination-associated nephrotoxicity was reviewed in 491 granulocytopenic patients with cancer and fever. Nephrotoxicity was defined as a rise in the serum creatinine level of more than 0.4 mg/dL. The different aminoglycosides, when combined with ticarcillin disodium, were found to have an equivalent nephrotoxic potential and, for the purpose of analysis, were combined and termed "aminoglycoside plus ticarcillin" (Ags + ticarcillin). Groups treated with gentamicin or amikacin plus cephalothin sodium were combined and termed "aminoglycoside plus cephalothin" (Ags + cephalothin). The rate of nephrotoxicity was statistically less for the Ags + ticarcillin group, eight (3.1%) of 262 patients, than for the Ags + cephalothin group, 23 (18.3%) of 126 patients. Age greater than 50 years was a potentiating factor for the occurrence of nephrotoxicity in the Ags + cephalothin group. We have concluded that for granulocytopenic patients with cancer and fever, the antibiotic combination of the Ags + cephalothin should not be used as empiric antibiotic therapy.

Adolescent↗