From the Infectious Diseases Society of America. Guidelines for the use of antimicrobial agents in neutropenic patients with unexplained fever.
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Agranulocytosis↗
Biomedical subjects
S C Schimpff
Publications and source records attributed to S C Schimpff.
Prevention of and therapy for infection in cancer patients.
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Agranulocytosis↗
Oral complications of cancer therapies. Surveillance cultures.
Surveillance cultures can be defined as an attempt to take microbiologic inventory, usually for bacteria and fungi, occasionally for viruses, at predetermined times during a patient's clinical course. They are useful in understanding the epidemiology of infection, evaluating techniques of infection prevention, assaying the effectiveness of preventive techniques, and guiding therapeutic decisions when empiric antimicrobial therapy is indicated. As such, they are most frequently used for patients at high risk of infection, such as those with acute leukemia receiving remission induction chemotherapy or bone marrow transplantation therapy. The sites sampled most frequently for surveillance cultures are the nose, oral cavity (pharynx or gingiva), and either the perianum or a stool specimen. Since hospital microbiology laboratories are not designed for the requirements of surveillance culturing, it is essential that such cultures only be obtained following appropriate communication and agreement with the laboratory directors.
Bacteria↗
Dilemmas and choices in infection management of the cancer patient.
Dilemmas related to fever and infection in the granulocytopenic cancer patient demand management choices frequently in the face of inadequate data to assure confidence in the decision taken. Key elements to decision-making include: recognition of the types of infections which tend to occur in these patients within one's own institution and the usual antimicrobial susceptibility patterns of the common pathogens within one's own institution. Second, one must differentiate the moderately granulocytopenic patient from one likely to have profound, persistent granulocytopenia and, hence, a high risk of mortality from gram-negative rod bacteremia. This information will assist in the selection of an initial empiric regimen. The same information in conjunction with the results of surveillance cultures and especially the results of repeat daily history and physical examination will assist in decisions related to discontinuation of the initial antibiotics, alterations in the original regimen, and decisions related to possible superinfections.
Agranulocytosis↗
Venous access devices utilized in association with intensive cancer chemotherapy.
Consistent and reliable venous access is a major component of the management of patients with cancer undergoing chemotherapy. Venous access devices such as the long-term right atrial catheter and the subcutaneous port have become a major aspect of the supportive care of such individuals, with resultant advantages which have improved their quality of life. Yet, the occurrence of infectious and non-infectious complications restricts the usefulness of these devices and warrants a standardized approach to device placement, patient education and the management of such complications. Infectious complications, including exit site and tunnel infections, as well as bacteremias requiring catheter removal occur at a rate of approximately two episodes for every 1000 catheter days, while non-infectious complications occur more frequently. Uniform patient education and catheter care, as well as placement by a single consistent surgeon will decrease the frequency of complications, improve the longevity and function of these venous access devices, while minimizing the associated morbidity.
Antineoplastic Agents↗
Aspergillus sinusitis in neutropenic patients with cancer: a review.
Aspergillosis typically occurs in patients with reduced host defenses; such patients include renal and marrow recipients as well as patients with chemotherapy-induced myelosuppression. Pulmonary structures are most frequently involved; non-pulmonary involvement (including sinus) has not been frequently reported. In the present study, paranasal sinusitis occurred in 52 myelosuppressed cancer patients treated over 5 years at the UMCC with chemotherapy. Twenty-one patients had Aspergillus sinusitis; Aspergillus spp., including flavus and niger, were directly recovered from sinus in 19 of the 21 infections. Two other patients were considered clinically, although not microbiologically, documented. Multiple predisposing factors for Aspergillus sinusitis during the 60 days prior to infection diagnosis appear to exist; these include: 1) granulocyte count less than 500 mm3 (mean duration, 42 days versus 14 days for sinusitis of other etiology; P less than 0.001); 2) prolonged hospitalization (mean duration, 22 days versus 14 days for patients with non-fungal sinusitis; P less than 0.001); and 3) prolonged antibiotic therapy (mean duration, 22 days versus 9 days; P less than 0.001). The Aspergillus sinusitis resolved in 18 of 21 patients following treatment with amphotericin B; however, 11 of 18 patients had infection recurrence that always developed when tumor recurred and chemotherapy was reinstituted.
Agranulocytosis↗
Empiric antimicrobial therapy for febrile granulocytopenic cancer patients: lessons from four EORTC trials.
The results of the four EORTC trials conducted over the past 15 years suggest: (1) early empiric therapy with broad spectrum antibiotics directed against gram-negative bacterial bacteremia (GNBB) is a reasonable approach in febrile granulocytopenic patients (GCP); (2) the level and dynamics of the granulocyte count are extremely important in determining the outcome of bacteremia; severely and/or persistently neutropenic patients are the true tests of antibiotic efficacy and they benefit from antimicrobial synergism; (3) mortality from GNBB in GCP is not related directly to a given empiric antimicrobial regimen which may 'buy time' and allow appropriate therapeutic alterations; (4) only microbiologically documented infections and especially bacteremias are useful to compare responses to antimicrobial regimens; (5) the response rate of GNBB is clearly influenced by the susceptibility of the causative pathogen to the beta-lactam component of the empiric regimen and emergence of resistance to some antibiotics (cephalothin, carbenicillin, ticarcillin, azlocillin) has rendered some combinations less effective. The combination of an anti-Pseudomonas beta-lactam plus an aminoglycoside is recommended as the 'standard' for empiric therapy in febrile GCP; (6) gram-positive pathogens have become a common cause of bacteremia in GCP and although the response rate to empiric regimens may be marginal, the associated mortality is low. A general conclusion from these trials is that studies of the management of infection in GCP should include sufficient numbers of eligible patients to allow for evaluation of bacteremic patients at highest risk of death. The need for large collaborative studies stems directly from these considerations.
Agranulocytosis↗
Epithelioid granulomas revisited: long-term follow-up in Hodgkin's disease.
A previous retrospective study of epithelioid granulomas discovered in the liver or spleen at staging laparotomy for Hodgkin's disease showed that the granulomas were not indicative of malignant involvement of these organs. Rather, they correlated with improved relapse-free survival in affected patients compared to those without granulomas. These findings were based on 2 year median follow-up. To confirm and expand these findings after additional follow-up, we analyzed the clinical data for 89 of the original cohort of 91 patients who underwent staging laparotomy at our institution between July, 1968 through December, 1972. Neither time to first relapse nor overall survival duration is now significantly different between the granuloma and nongranuloma groups. Of the nongranuloma patients 23/67 (34%) have relapsed versus 3/16 (19%) patients with granulomas (Fisher's exact test p = 0.184). The relapse-free survival advantage for patients with granulomas seen in the earlier report is no longer apparent after more prolonged follow-up.
Adult↗
Microbiology of acute periodontal infection in myelosuppressed cancer patients.
This study characterized the subgingival microbial flora associated with 27 acute exacerbations of preexistent periodontal disease in 24 patients with chemotherapy-induced myelosuppression. All but two acute periodontal infections developed at low granulocyte levels (less than 1,000/microL). Suspected pathogens were detected in high concentrations in subgingival plaque specimens in 17 episodes of acute periodontal infection; a single pathogen was recovered in ten acute infections, and more than one pathogen was recovered in seven acute infections. Staphylococcus epidermidis, Candida albicans, S aureus, and Pseudomonas aeruginosa predominated, with combinations of these detected in some patients. Concomitant bacteremias developed in two of these patients. The subgingival microflora associated with ten acute periodontal infections was characterized by predominantly indigenous microorganisms, which in nine episodes were in abnormal proportions compared with microbial profiles in noncancer patients with similar degrees of periodontal disease. These data demonstrate that pathogens normally associated with infections in myelosuppressed cancer patients, as well as indigenous oral flora, are associated with acute periodontal infections during granulocytopenia. This finding is important, since this body site has not commonly been recognized as a source for acute infection in these patients.
Acute Disease↗
Aspergillus sinusitis in cancer patients.
Paranasal sinusitis occurred in 52 immunosuppressed cancer patients treated over 5 years at the University of Maryland Cancer Center. Twenty-one patients had aspergillus sinusitis; Aspergillus sp, including flavus and niger were directly recovered from sinus in 19 of the 21 infections. Two other patients with sinus involvement and positive nose cultures for Aspergillus flavus or fumigatus and microbiologically documented pulmonary aspergillosis were considered clinically, although not microbiologically, documented. Predisposing factors for aspergillus sinusitis during the 60 days prior to infection diagnosis were granulocyte count less than 500 microliter (mean duration, 42 days versus 14 days for sinusitis of other etiology; P less than 0.001), prolonged hospitalization (mean duration, 22 days versus 14 days for patients with nonfungal sinusitis; P less than 0.001), and prolonged antibiotic therapy (mean duration, 22 days versus 9 days; P less than 0.001). Treatment with amphotericin B was initially successful for 18 of 21 patients; however, 11 of 18 patients had infection recurrence that always developed at time of tumor exacerbation and reinstitution or intensification of chemotherapy. These findings suggest that aspergillus sinusitis in cancer patients is seen in association with prolonged neutropenia and antibiotic therapy, is amenable to therapy, but tends to recur with relapse of malignancy.
Adult↗
A double beta-lactam combination versus an aminoglycoside-containing regimen as empiric antibiotic therapy for febrile granulocytopenic cancer patients.
The double beta-lactam combination of moxalactam plus piperacillin was compared with the aminoglycoside-containing regimen of moxalactam plus amikacin in a prospective, randomized trial of empiric therapy for 302 febrile episodes in granulocytopenic cancer patients. The moxalactam/piperacillin regimen was found to be as effective as the moxalactam/amikacin regimen (70 percent overall responses); responses with moxalactam/piperacillin and moxalactam/amikacin were similar for microbiologically documented infections (24 of 37, 65 percent, versus 20 of 35, 57 percent), for the subgroup with bacteremias (19 of 32 versus 14 of 28), and for clinically documented infections (41 of 58, 71 percent, versus 40 of 48, 83 percent). Responses were similar also for bacteremia in patients with persistent, profound (less than 100/microliter) granulocytopenia. Among profoundly (less than 100/microliter) granulocytopenic patients with gram-negative bacteremia, an increase in the granulocyte count to more than 100/microliter during therapy and a peak bactericidal activity of 1:16 or more (the latter noted in seven of nine moxalactam/piperacillin trials and six of nine moxalactam/amikacin trials) correlated with a favorable clinical response in 85 percent (p less than or equal to 0.00003) and 92 percent (p less than or equal to 0.044), respectively. Although serious side effects were minimal with either regimen, the double beta-lactam combination was associated with significantly less frequent nephrotoxicity (two of 145 versus 12 of 130; p less than or equal to 0.003) and ototoxicity (none of 34 versus seven of 34; p less than or equal to 0.006). The double beta-lactam combination of moxalactam plus piperacillin was found to be as effective as moxalactam plus amikacin but to have significantly less nephro- and ototoxicity.
Adolescent↗
Empiric antibiotic therapy for granulocytopenic cancer patients.
Many cancer patients become granulocytopenic as a result of therapy and, as such, are likely to have fever during neutropenic episodes. Approximately 20 percent of these episodes have an associated gram-negative rod bacteremia; these infections occur among the most profoundly granulocytopenic patients and are associated with the highest mortality. Most infections are caused by one of three organisms: Escherichia coli, Pseudomonas aeruginosa, or Klebsiella pneumoniae. The standard approach to therapy has been the empiric utilization of an antibiotic combination, most often an aminoglycoside with either an anti-Pseudomonas penicillin or a cephalosporin. In patients for whom concern about aminoglycoside-associated nephro- or ototoxicity is high, a double beta-lactam combination has been considered. Also, with the introduction of increasingly active, exceptionally broad-spectrum antimicrobials, empiric therapy with single agents has been considered. Beta-lactam/aminoglycoside combinations more often than not are synergistic, although antagonism can be detected on occasion. Some double beta-lactam combinations demonstrate antagonism, whereas in other cases, synergism, or at least partial synergism, can be observed. Antibiotic combinations can be evaluated through in vitro models, such as the capillary model system, or through animal models designed to mimic the neutropenic state with gram-negative bacteremia, to determine potential agents or combinations of agents for this patient population. These preclinical approaches have suggested that some agents may prove effective as monotherapy and, indeed, have been comparable in activity to some of the standard antibiotic combinations. However, clinical trials have had insufficient numbers of particularly high-risk patients with profound, persistent granulocytopenia and gram-negative rod bacteremia to be able to assess their usefulness in such patients. In general, it still appears to be advantageous to use combinations such as those used in the most recent European Organization for Research on Treatment of Cancer antimicrobial trial, which compared azlocillin/amikacin with ceftazidime/amikacin. In order to reduce aminoglycoside toxicity, patients were randomly assigned to receive amikacin either for a short period or for the entire length of therapy. The study should help to determine whether it is possible to maintain the advantages of two-drug combinations while reducing the disadvantages of prolonged aminoglycoside therapy.
Agranulocytosis↗
Antibiotic synergism and response in gram-negative bacteremia in granulocytopenic cancer patients.
To determine whether antimicrobial synergism affects the outcome of gram-negative bacteremia among profoundly (less than 100/microliter) neutropenic cancer patients, the clinical courses of 75 such patients who received empiric therapy with combination, broad-spectrum antibiotics were analyzed. Twenty-nine of 34 (85 percent) patients whose granulocyte count increased to more than 100/microliter during therapy improved, whereas only 12 of 41 (29 percent) patients with no increase in granulocyte count showed improvement (p = 0.0002). The critical group for further analysis was, therefore, those patients with persistent, profound granulocytopenia. Among these 41 patients, synergism was associated with a substantially better response rate: eight of 18 (44 percent) improved compared with none of 13 in whom synergism was not detected (p = 0.005); presence or absence of synergism could not be assessed for the pathogens isolated from the remaining 10 patients because the organisms were exquisitely susceptible to one of the two antibiotics used. Further evaluation of these persistently neutropenic patients indicated that synergism appeared critical even when the pathogen was susceptible to both antibiotics. Thus, seven of 11 (64 percent) showed response when the two drugs were synergistic in activity, compared with none of six when synergism was not present (p = 0.01). These data again demonstrate the importance of granulocyte recovery to patient response and further indicate that synergistic combinations of antibiotics are indicated for cancer patients with gram-negative bacteremia and persistent, profound granulocytopenia.
Agranulocytosis↗
Serum bactericidal test in volunteers--a review.
A review is given of work utilizing the serum bactericidal test for preclinical evaluation of agents considered for treatment of gram-negative sepsis among neutropenic cancer patients. Following a description of the methodology of the two major groups, the results of the various antibiotic trials are summarized. First the extended-spectrum cephalosporins (cefotaxime, cefoperazone, and moxalactam) were tested and found to be, at best, of limited value as single agents for Pseudomonas aeruginosa, a common pathogen of neutropenic cancer patients. When the extended-spectrum penicillins became available, the serum bactericidal levels in volunteers of mezlocillin and piperacillin were compared alone or in combination with an aminoglycoside to ticarcillin with or without aminoglycoside against the same organisms. Piperacillin proved to be most effective followed by mezlocillin and then ticarcillin; in each case the addition of the aminoglycoside improved serum bactericidal activity. Recent studies suggest that imipenem alone is as active as the combination of a broad-spectrum penicillin plus an aminoglycoside and is worthy of a carefully controlled clinical trial. These types of volunteer-based evaluations of the serum bactericidal activity of new compounds may help predict useful clinical approaches for the future.
Adult↗
Molecular epidemiology of group JK Corynebacterium on a cancer ward: lack of evidence for patient-to-patient transmission.
Plasmid profiles of 27 clinical isolates of group JK Corynebacterium, mostly from one cancer ward, revealed that only two strains harbored a 20-kilobase plasmid. These plasmid-bearing isolates had the same antimicrobial resistance pattern as non-plasmid-containing isolates: All were resistant to penicillin G, methicillin, cephalothin, clindamycin, and gentamicin. Restriction endonuclease analysis of chromosomal DNA was done on 18 clinical isolates of group JK Corynebacterium. Identical restriction patterns were seen when multiple isolates were from the same patient over several months of apparent colonization; in contrast, restriction patterns of isolates from patients from two clusters were all heterogeneous and suggested that patient-to-patient transmission of group JK Corynebacterium did not occur. Restriction endonuclease analysis of chromosomal DNA, but not plasmid profiling, appears to be a very sensitive typing tool for group JK Corynebacterium.
Corynebacterium↗
Special studies of the Hickman catheter of a patient with recurrent bacteremia and candidemia.
A patient with acute non-lymphocytic leukemia developed Staphylococcus epidermidis bacteremia and candidemia after maintenance chemotherapy and was treated satisfactorily. He returned 3 months later with abdominal pain due to an abdominal aortic aneurysm. At laparotomy, the aneurysm was found to be infected with Candida albicans. Following surgery, repeated positive blood cultures for C. albicans led to removal of his Hickman catheter. Culture of the catheter tip yielded C. albicans and S. epidermidis. Study of the catheter by scanning and transmission electron microscopy demonstrated yeast-like cells and gram-positive cocci in a biofilm. These studies suggest that the Hickman catheter was the source of the persistent candidemia and that it may have been the origin of the infection of the aneurysm.
Antineoplastic Agents↗
Prospective randomized comparison of three antibiotic regimens for empirical therapy of suspected bacteremic infection in febrile granulocytopenic patients.
The standard regimen used by members of the European Organization for Research on Treatment of Cancer Antimicrobial Therapy Cooperative Group for empiric therapy of febrile neutropenic cancer patients has been treatment with ticarcillin plus amikacin. A three-arm prospective randomized controlled trial was performed to determine whether the extended-spectrum antipseudomonal penicillin azlocillin or the extended-spectrum cephalosporin cefotaxime had more or less efficacy than the beta-lactam in the ticarcillin-plus-amikacin regimen. A total of 742 patients from 22 institutions were evaluated. Single gram-negative rod bacteremias accounted for 83 episodes, and it was among these patients that the prognosis was least satisfactory, leading to a more intensive evaluation of this patient group. In these patients the azlocillin-plus-amikacin regimen resulted in a 66% response rate, compared with a 37% response rate for patients who received cefotaxime plus amikacin (P = 0.080) and a 47% response rate for patients who received ticarcillin plus amikacin (P = 0.207). The patients with gram-negative rod bacteremias and persistently profound granulocytopenia had substantially poorer response rates (37%) than the patients with rising granulocyte counts (73%; P = 0.004). A logistic regression analysis indicated that the following factors also affected infection resolution: beta-lactam utilization in the regimen (azlocillin was better than ticarcillin or cefotaxime), resolution of profound granulocytopenia (less than 100 cells per microliter) during therapy, and susceptibility to the beta-lactam antibiotic.
Adolescent↗
Adherent microorganisms on lumenal surfaces of long-term intravenous catheters. Importance of Staphylococcus epidermidis in patients with cancer.
Using electron microscopy, we prospectively evaluated how frequently adherent microorganisms colonized silicone rubber intravenous (Hickman) catheters removed from patients with cancer. Thirteen (87%) of 15 catheters had gram-positive cocci in glycocalyx adherent to the surface of the catheter lumen. Fungal elements or gram-negative bacilli were mixed with the gram-positive cocci in the glycocalyx on the lumens of three catheters. A consistent morphologic form was adherent to, and the same species was recovered from, the corresponding catheter for six of 27 organisms causing septicemia during catheterization: four of five Staphylococcus epidermidis bacteremias and the only Staphylococcus aureus bacteremia, and one of five candidemias. Three of these six septicemias were successfully treated without removal of the catheter. Although adherent organisms, particularly S epidermidis, were likely to be present on the surface of the lumen of long-term, indwelling, silicone intravenous catheters, septicemias potentially related to these organisms occurred infrequently (fewer than two per 1000 days of catheter use), and the suspect septicemias could sometimes be treated without removal of the catheter.
Adult↗