From the Infectious Diseases Society of America: Guidelines for the Use of Antimicrobial Agents in Neutropenic Patients with Unexplained Fever

Hughes, Walter T.; Armstrong, Donald; Bodey, Gerald P.; Feld, Ronald; Mandell, Gerald L.; Meyers, Joel D.; Pizzo, Phillip A.; Schimpff, Stephen C.; Shenep, Jerry L.; Wade, James C.

doi:10.1093/infdis/161.3.381

Cited by 394 publications

(101 citation statements)

References 96 publications

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“…The results of our study are in accord with the clinical truism that successful antimicrobial therapy varies with the severity of the bacterial infection. This clinical experience is most evident in granulocytopenic patients (Love, Schimpff & Schiffer, 1980;Hughes et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

“…Some of these factors, such as the infecting microorganisms, the site of infection and the intrinsic activity of an antimicrobial agent and its pharmacokinetic behaviour, have been well recognized and investigated in experimental models of infection (Drusano, 1991). On the other hand, the age of the infection (the pre-treatment interval) and the density of the infecting organisms have hardly been investigated, although their impact on overall success of an antimicrobial treatment can be assumed from clinical observation in such diseases as Gram-negative septicaemia in the granulocytopenic host (Hughes et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

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The impact of the pre-treatment interval on antimicrobial efficacy in a biological model

Gerber

Greter

Segessenmann

et al. 1993

Journal of Antimicrobial Chemotherapy

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The impact of pre-treatment intervals on the antipseudomonal efficacy of gentamicin, ticarcillin and ceftazidime was studied in an experimental thigh infection model in normal and granulocytopenic mice. Human-equivalent doses were used for simulating human pharmacokinetic profiles of the two study 0-lactam drugs. A lethal inoculum of a virulent strain of Pseudomonas aeruginosa was injected into the thigh muscle. Treatment was started at various post-infection intervals. Antimicrobial efficacy was assessed by determinations of surviving organisms at the site of infection, and plasma drug concentrations were determined in the same mice. The age of infection had a substantial impact on antipseudomonal efficacy of the three study drugs even though high, brief supra-MIC concentrations of gentamicin and persistent supra-MIC concentrations of the /Mactam drugs were obtained. A pre-treatment interval of six or more hours abolished the bactericidal effect of all three study drugs despite accumulation of the drugs to multiple-MBC plasma concentrations. We believe that the impact of pre-treatment intervals on antimicrobial efficacy is of paramount importance for the interpretation of antimicrobial activity studies in experimental models of infection, although the mechanisms remain to be elucidated.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The impact of the pre-treatment interval on antimicrobial efficacy in a biological model

Gerber

Greter

Segessenmann

et al. 1993

Journal of Antimicrobial Chemotherapy

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“…Patients with severe neutropenia (Ͻ100 granulocytes/ mm 3 ) are at greatest risk (9,10), and the mortality rate for patients developing pneumonia in this setting can be as high as 67% (4). With the advent of stem cell transplantation and the use of colonystimulating factors, the duration of neutropenia post-BMT has been significantly shortened (11)(12)(13)(14)(15). Despite this, immunodeficiency can persist, and patients remain at increased risk for pulmonary infections.…”

Section: Defective Phagocytosis and Clearance Of Pseudomonas Aeruginomentioning

confidence: 99%

Defective Phagocytosis and Clearance of Pseudomonas aeruginosa in the Lung Following Bone Marrow Transplantation

Ojielo

Cooke²,

Mancuso

et al. 2003

The Journal of Immunology

128

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Bone marrow transplantation (BMT) is an important therapeutic option for a variety of malignant and nonmalignant disorders. Unfortunately, BMT recipients are at increased risk of infection, and in particular, pulmonary complications occur frequently. Although the risk of infection is greatest during the neutropenic period immediately following transplant, patients are still vulnerable to pulmonary infections even after neutrophil engraftment. We evaluated the risk of infection in this postengraftment period by using a well-established mouse BMT model. Seven days after syngeneic BMT, B6D2F1 mice are no longer neutropenic, and by 3 wk, they demonstrate complete reconstitution of the peripheral blood. However, these mice remain more susceptible throughout 8 wk to infection after intratracheal administration of Pseudomonas aeruginosa; increased mortality in the P. aeruginosa-infected BMT mice correlates with increased bacterial burden in the lungs as well as increased systemic dissemination. This heightened susceptibility to infection was not secondary to a defect in inflammatory cell recruitment to the lung. The inability to clear P. aeruginosa in the lung correlated with reduced phagocytosis of the bacteria by alveolar macrophages (AMs), but not neutrophils, decreased production of TNF-α by AMs, and decreased levels of TNF-α and IFN-γ in the bronchoalveolar lavage fluid following infection. Expression of the β2 integrins CD11a and CD11c was reduced on AMs from BMT mice compared with wild-type mice. Thus, despite restoration of peripheral blood count, phagocytic defects in the AMs of BMT mice persist and may contribute to the increased risk of infection seen in the postengraftment period.

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“…Disruption of the mucosal barrier opens the door to consecutive, often life-threatening infectious complications during neutropenia. [9][10][11][12] From the patient's point of view, oral mucositis is one of the major distressing complications of cancer therapy. In addition, severe oral mucositis and subsequent complications may lead to a delay in cancer therapy and dosereduction of antineoplastic agents, which might result in an unfavourable outcome of the cancer treatment.…”

mentioning

confidence: 99%

Prophylaxis and treatment of chemo- and radiotherapy-induced oral mucositis – are there new strategies?

Karthaus

Rosenthal

Ganser

1999

Bone Marrow Transplant

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Summary:Oral mucositis is a major dose-limiting toxic effect of intensive cancer chemotherapy. Oral complications may lead to dose reduction or delay in further cancer treatment. Mucositis can be caused directly by cytotoxic effects and indirectly by sustained neutropenia after cytostatic therapy. An impaired mucosal barrier predisposes to life-threatening septic complications during aplasia. The prevalence of an oral focus in febrile neutropenia has been reported in up to 30% of cases and also reduces quality of life. The basic strategies aim at pain relief and prevention of bacterial and fungal infectious complications. However, no effective causal prophylaxis or treatment of oral mucositis is widely accepted. The introduction of cytokines, eg granulocytemacrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) for oral mucositis may be particularly effective and offer a new and hopeful approach. At present, the optimal growth factor, best schedule, effective dosage and best mode of application is not known.

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From the Infectious Diseases Society of America: Guidelines for the Use of Antimicrobial Agents in Neutropenic Patients with Unexplained Fever

Cited by 394 publications

References 96 publications

The impact of the pre-treatment interval on antimicrobial efficacy in a biological model

The impact of the pre-treatment interval on antimicrobial efficacy in a biological model

Defective Phagocytosis and Clearance of Pseudomonas aeruginosa in the Lung Following Bone Marrow Transplantation

Prophylaxis and treatment of chemo- and radiotherapy-induced oral mucositis – are there new strategies?

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