Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gram-negative infections in neutropenic patients originate frequently from the gut flora. Attempts to decrease the incidence of these infections have utilized several regimens for gastrointestinal decontamination, of which some have proven to be clinically useful. Orally administered nonabsorbable antibiotics (aminoglycosides, polymyxins) can decrease the incidence of gram-negative sepsis during neutropenia, but, with the possible exception of netilmicin, tolerance to these agents is generally poor, and compliance is low. Trimethoprim-sulfamethoxazole has been used widely for the prophylaxis of infections in neutropenic patients. Clinical results with this agent have been conflicting, as its efficacy is clearly related to epidemiological patterns of resistance of the pathogens in the population under study. More recently, the quinolones, which are well tolerated by patients and are presently active on most strains of Enterobacteriaceae, have been associated with a virtual eradication of gram-negative infections in neutropenic patients. These results have been paralleled by an increase in the frequency of gram-positive infections, which, fortunately, cause an incidence of mortality that is much lower than that seen in gram-negative sepsis. The fact that the quinolones are absorbed systemically might help to explain their efficacy in chemoprophylaxis during neutropenia. This paper discusses the chemoprophylaxis of gram-negative infection during neutropenia in the light of theoretical concepts such as 'colonization resistance', 'selective decontamination', and 'bacterial translocation'.
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PMID:Chemoprophylaxis of gram-negative infections in neutropenic patients. 216 99

Trimethoprim and sulfamethoxazole (Bactrim r) is a widely used antibiotic combination effective against a broad spectrum of microbial organisms. There are reports of neutropenia developing during even brief periods of oral therapy, particularly in individuals with either folate deficiency or increased folate requirements. We have investigated the effects of these drugs on circulating granulocyte precursors (CFU-C) from normal donors and the mechanism of inhibition on granulopoiesis using an in vitro CFU-C assay. In 12 healthy adults, the number of circulating granulocytes and granulocyte progenitors was not significantly altered by a 5-day course of therapy. However, in experiments that simulated the in vivo condition of folate deficiency (folate-free cultures were prepared with cells harvested from normal donors), trimethoprim (8 micrograms/ml) resulted in a 47% decrease in the total number of colonies; this inhibitory effect was prevented when 100 ng of folinic acid was also added to the culture. Sulfamethoxazole (40 micrograms/ml) had no discernible effect on granulopoiesis. The combination of 8 micrograms/ml of trimethoprim and 40 micrograms/ml of sulfamethoxazole resulted in a 52% decrease in the number of colonies generated and this inhibition was again prevented by folinic acid. Our results suggest that the neutropenia occasionally observed in patients treated with trimethoprim-sulfamethoxazole is due to the inhibitory effects on granulopoiesis by trimethoprim, namely its antifolate action, which is reversed by folinic acid. Based on these studies, in patients with either folate deficiency or increased folate requirements, trimethoprim-sulfamethoxazole should be used with caution.
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PMID:Studies of the effects of trimethoprim and sulfamethoxazole on human granulopoiesis. 348 80

Oral trimethoprim-sulfamethoxazole (Bactrim) plus erythromycin (TMZ-E) was tested versus placebo (P) as prophylaxis for bacterial infection in a randomized, double-blind trial in adult cancer patients receiving cytotoxic chemotherapy expected to result in significant neutropenia. The incidence of adverse reactions attributable to TMZ and/or E was higher in drug-treated episodes (18 of 28 vs 3 of 29 for P, P less than 0.0005) resulting in poorer compliance. The incidence of fever was not significantly different between episodes treated with TMZ-E (18/27) and those treated with P (17/29), nor was there a significant difference in the median interval between the onset of neutropenia and the onset of fever. However, 14 of 18 fevers in TMZ-E recipients were without a documented infectious source compared with only 6 of 17 in P recipients (P less than 0.05). The same patterns were apparent even when episodes in which compliance with the regimen was either excellent or good were considered separately. There was no significant difference in the number of deaths from infection between TMZ-E and P recipients (3/27 vs 1/29). It is concluded that TMZ-E prophylaxis is of no practical benefit, may mask the cause of infection in febrile neutropenic cancer patients, and is associated with substantial toxicity.
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PMID:Prophylaxis of fever and infection in adult cancer patients. A placebo-controlled trial of oral trimethoprim-sulfamethoxazole plus erythromycin. 641 74

We identified 91 cases of bacteremia due to Stenotrophomonas (Xanthomonas) maltophilia in a prospective, multicenter observational study. The patients were highly compromised; the majority had an underlying malignancy, had received immunosuppressive therapy, and had indwelling venous catheters. Although 94% of patients received an antimicrobial agent to which the blood isolate was susceptible, the mortality among these patients 14 days after the onset of bacteremia was 21%. Mortality was significantly correlated with the presence of a hematologic malignancy or neutropenia or transplantation, immunosuppressive therapy, and a severity-of-illness score of > 4. S. maltophilia infection is associated with substantial morbidity and mortality among highly compromised patients. The organism is typically resistant to expanded spectrum beta-lactam agents and aminoglycoside antibiotics. Trimethoprim-sulfamethoxazole should be administered if the isolate is susceptible to this combination; addition of another agent to which the isolate is susceptible should be considered in treating patients who are neutropenic, immunocompromised, or critically ill.
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PMID:Bacteremia due to Stenotrophomonas (Xanthomonas) maltophilia: a prospective, multicenter study of 91 episodes. 885 71

Antibiotics generally considered for antibacterial prophylaxis for immunosuppressed patients are trimethoprim-sulfamethoxazole and the quinolones. Trimethoprim-sulfamethoxazole can significantly reduce infections and is highly effective in preventing pneumonia due to Pneumocystis carinii. However, it can cause sulfonamide-related reactions, myelosuppression, oral candidiasis, and development of bacterial resistance, and it lacks activity against Pseudomonas aeruginosa. Quinolones can reduce the occurrence of fever and infections in patients with neutropenia but do not provide adequate coverage against gram-positive bacteria, and inappropriate use can induce resistance among gram-negative organisms. Routine antibacterial prophylaxis is not recommended for patients likely to develop neutropenia. Antifungal prophylaxis is appropriate in settings in which fungal infections are frequent. Fluconazole is recommended for patients who are to undergo hematopoietic stem cell transplantation; it can be considered for elderly patients with acute leukemia who are to receive intensive chemotherapy. Itraconazole can also be used. Prophylaxis with antiviral agents is generally not indicated; however, it should be given to hematopoietic stem cell transplant recipients.
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PMID:Antimicrobial prophylaxis in febrile neutropenia. 1525 25

Trimethoprim-sulfamethoxazole (TMP-SMX) is a combination chemotherapeutic agent, a commonly used antibiotic. Adverse drug reactions occur in 6-8% of patients. Although, the most common adverse reactions include mild gastrointestinal distress and cutaneous events, also a wide range of hematological abnormalities have been ascribed to TMP-SMX. We report a 40-year-old male patient who developed an early onset neutropenia, thrombocytopenia, generalised rash and oral candidiasis after 5 days long TMP-SMX therapy. Although generalised rash may seen more and improves with discontinuation of the therapy; severe neutropenia, thrombocytopenia and oral candidiasis are seen very rare and rarely leads to fatality as it was in our case. Despite thrombocyte transfusions, whole blood transfusions, red cell concentrates and filgrastim therapy we lost our patient. We want to underline that although the TMP-SMX combination is usually well tolerated it can also lead to fatal complications.
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PMID:Trimethoprim-sulfamethoxazole induced rash and fatal hematologic disorders. 1599 41

During a 15-month retrospective clinical study in an academic referral-based cancer center, 26 patients with S. maltophilia respiratory tract infections were identified (which were associated with bacteremia in 13 patients). Five of these 26 patients had previously undescribed sinopulmonary involvement. The infections were typically nosocomial. Nine patients with solid tumors had malignant involvement of the respiratory tract (five with obstruction). In two patients, the infection co-existed with pulmonary aspergillosis. Fifteen patients (58%) died of the infection. The factors that correlated with a poor outcome included bacteremic pneumonia, persistent neutropenia, presence of obstruction, development of septic shock or multiple organ dysfunction, and delay in institution of appropriate antibiotic therapy. In multivariate analysis, only septic shock and delayed therapy remained significant. Trimethoprim-sulfamethoxazole and/or ticarcillin-clavulanate were most commonly associated with a favorable outcome.
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PMID:The clinical spectrum of stenotrophomonas (xanthomonas) maltophilia respiratory infection. 1608 46

Patients with cancer and chemotherapy-induced neutropenia are at risk for severe bacterial infections. This risk is not uniform among all cancer patients but is dependent primarily on the depth and duration of neutropenia and the type of underlying disease. Accordingly, the decision whether to use antibacterial prophylaxis to prevent serious infections in these patients requires a balance between expected benefit and the risks for infection, adverse drug-related events, and emergence of antibiotic resistance. Although antibacterial prophylaxis has the potential to benefit all patients with chemotherapy-induced neutropenia, the benefit regarding reduction in documented infections has been firmly established only in patients with neutropenia expected to exceed 7 days. A recent meta-analysis showed enhanced survival in patients receiving antibacterial prophylaxis during neutropenia; most patients enrolled in the analyzed trials had a hematologic malignancy. Among patients with neutropenia at lower risk for infectious complications (a category that includes most patients with solid tumor malignancies), the main benefit of antibacterial prophylaxis relates to a reduction in fever rather than documented infections. The authors advise quinolone prophylaxis (levofloxacin is preferred), in patients with an expected duration of neutropenia (absolute neutrophil count < 1000/microL) of more than 7 days. Trimethoprim-sulfamethoxazole should be used in patients at risk for Pneumocystis jiroveci (formerly P carinii), such as childhood acute lymphoblastic leukemia. In patients with neutropenia expected to last 7 days or less and not receiving immunosuppressive regimens (e.g., systemic corticosteroids), the authors recommend no initial prophylaxis. However, if such patients develop fever during neutropenia, they should be considered for outpatient empiric therapy with an oral quinolone-containing regimen if they meet criteria for low risk for complications.
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PMID:Antibacterial prophylaxis in patients with neutropenia. 1733 92

Pneumocystis jiroveci (formerly carinii) pneumonia (PCP) is a serious opportunistic infection in children and adolescents with cancer. It was the most common cause of death among children receiving chemotherapy prior to the inclusion of PCP prophylaxis as part of standard care for children with leukemia. The incidence of PCP has decreased significantly since initiation of prophylaxis; however, breakthrough cases continue to occur. Hematologic malignancies, brain tumors necessitating prolonged corticosteroid therapy, hematopoietic stem cell transplantation, prolonged neutropenia, and lymphopenia are the most important risk factors for PCP in children not infected with HIV. Of children with leukemia, 15-20% may develop PCP in the absence of prophylaxis. Infection with P. jiroveci occurs early in life in most individuals. However, clinically apparent disease occurs almost exclusively in immunocompromised persons. Dyspnea, cough, hypoxia, and fever are the most common presenting symptoms of PCP. Chest radiography and high-resolution CT scans of the chest demonstrate a characteristic ground-glass pattern. Induced sputum analysis and bronchoalveolar lavage are the diagnostic procedures of choice. Gomori's methenamine-silver stain, Geimsa or Wright's stain, and monoclonal immunofluorescent antibody stains are most commonly used to make a diagnosis. However, identification of P. jiroveci DNA using polymerase chain reaction assays in bronchoalveolar lavage fluid is more sensitive. Trimethoprim-sulfamethoxazole (TMP-SMZ; cotrimoxazole) is the recommended drug for the treatment of PCP. Patients who are intolerant of TMP-SMZ or who have not responded to treatment after 5-7 days of therapy with TMP-SMZ should be treated with pentamidine. A short course of corticosteroids is recommended for moderate to severe cases of PCP within the first 72 hours after diagnosis. Mutations in the dihydropteroate synthetase gene may confer resistance to TMP-SMZ; however, the clinical relevance of these mutations is not well established. TMP-SMZ is the most commonly used agent for prophylaxis. Myelosuppression is the most important adverse effect of TMP-SMZ and the most frequent cause for choosing alternative prophylactic agents in children undergoing chemotherapy. Alternative agents for chemoprophylaxis include dapsone, aerosolized pentamidine, and atovaquone. Alternative prophylactic agents must be used in patients developing myelosuppression secondary to TMP-SMZ or dapsone.
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PMID:Management of Pneumocystis jiroveci pneumonia in children receiving chemotherapy. 1792 2

Stenotrophomonas maltophilia colonization/infection in patients with cancer has significantly increased over the past 2 decades. Patients with prolonged neutropenia, exposure to broad-spectrum antibiotics, and those requiring mechanical ventilation have higher risk of infection. These micro-organisms are intrinsically resistant to carbapenems, and exposure to these agents has been linked to selection of S. maltophilia. Recently, these infections are being documented in patients without traditional risk factors. The spectrum of infection includes bacteremia, catheter-related infection, pneumonia, complicated biliary and urinary tract infection, and skin and skin-structure infection. Trimethoprim-sulfamethoxazole is the therapeutic agent of choice, but resistance is increasingly being reported. Susceptibility to alternative agents is unpredictable. Combination therapy and alternative routes of drug administration, such as aerosolized aminoglycoside, might be necessary. New insights into the mechanisms of drug resistance might lead to identification of new target sites. Agents that improve outer-membrane permeability and broad-spectrum beta-lactamase inhibitors may favorably impact difficult-to-treat (i.e., multidrug resistant) S. maltophilia infections.
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PMID:Stenotrophomonas maltophilia: changing spectrum of a serious bacterial pathogen in patients with cancer. 1841 67


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