trimethoprim--sulfamethoxazole-drug-combination and Neoplasms

Pneumocystis jirovecii is the only fungus of its kind to be pathogenic in humans. It is primarily responsible for pneumonia (PJP). The key to understanding immune defences has focused on T-cells, mainly because of the HIV infection epidemic. Patients presenting with PJP all have a CD4 count below 200/mm(3). The introduction of systematic primary prophylaxis and the use of new anti-retroviral drugs have significantly reduced the incidence of this disease in the HIV-infected population, mainly in developed countries. The increasingly frequent use of corticosteroids, chemotherapy, and other immunosuppressive drugs has led to an outbreak of PJP in patients not infected by HIV. These patients presenting with PJP have more rapid and severe symptoms, sometimes atypical, leading to delay the initiation of a specific anti-infective therapy, sometimes a cause of death. However, the contribution of new diagnostic tools and a better understanding of patients at risk should improve their survival.

Topics: Adrenal Cortex Hormones; Antineoplastic Agents; beta-Glucans; Connective Tissue Diseases; Drug Therapy, Combination; Early Diagnosis; HIV Seronegativity; Humans; Immunocompromised Host; Immunologic Deficiency Syndromes; Immunologic Factors; Immunosuppressive Agents; Neoplasms; Organ Transplantation; Pneumocystis carinii; Pneumocystis Infections; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Postoperative Complications; Prognosis; Radiography; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii infection (PJP) is a common cause of pneumonia in patients with cancer-related immunosuppression. There are well-defined patients who are at risk of PJP due to the status of their underlying malignancy, treatment-related immunosuppression and/or concomitant use of corticosteroids. Prophylaxis is highly effective and should be given to all patients at moderate to high risk of PJP. Trimethoprim-sulfamethoxazole is the drug of choice for prophylaxis and treatment, although several alternative agents are available.

Topics: Adrenal Cortex Hormones; Antibiotic Prophylaxis; Consensus; Drug Administration Schedule; Humans; Immunocompromised Host; Neoplasms; Opportunistic Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Practice Guidelines as Topic; Trimethoprim, Sulfamethoxazole Drug Combination

Bacterial infections are a major cause of morbidity and mortality in patients who are neutropenic following chemotherapy for malignancy. Trials have shown the efficacy of antibiotic prophylaxis in reducing the incidence of bacterial infections but not in reducing mortality rates. Our systematic review from 2006 also showed a reduction in mortality.. This updated review aimed to evaluate whether there is still a benefit of reduction in mortality when compared to placebo or no intervention.. We searched the Cochrane Cancer Network Register of Trials (2011), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2011), MEDLINE (1966 to March 2011), EMBASE (1980 to March 2011), abstracts of conference proceedings and the references of identified studies.. Randomised controlled trials (RCTs) or quasi-RCTs comparing different types of antibiotic prophylaxis with placebo or no intervention, or another antibiotic, to prevent bacterial infections in afebrile neutropenic patients.. Two authors independently appraised the quality of each trial and extracted data from the included trials. Analyses were performed using RevMan 5.1 software.. One-hundred and nine trials (involving 13,579 patients) that were conducted between the years 1973 to 2010 met the inclusion criteria. When compared with placebo or no intervention, antibiotic prophylaxis significantly reduced the risk of death from all causes (46 trials, 5635 participants; risk ratio (RR) 0.66, 95% CI 0.55 to 0.79) and the risk of infection-related death (43 trials, 5777 participants; RR 0.61, 95% CI 0.48 to 0.77). The estimated number needed to treat (NNT) to prevent one death was 34 (all-cause mortality) and 48 (infection-related mortality).Prophylaxis also significantly reduced the occurrence of fever (54 trials, 6658 participants; RR 0.80, 95% CI 0.74 to 0.87), clinically documented infection (48 trials, 5758 participants; RR 0.65, 95% CI 0.56 to 0.76), microbiologically documented infection (53 trials, 6383 participants; RR 0.51, 95% CI 0.42 to 0.62) and other indicators of infection.There were no significant differences between quinolone prophylaxis and TMP-SMZ prophylaxis with regard to death from all causes or infection, however, quinolone prophylaxis was associated with fewer side effects leading to discontinuation (seven trials, 850 participants; RR 0.37, 95% CI 0.16 to 0.87) and less resistance to the drugs thereafter (six trials, 366 participants; RR 0.45, 95% CI 0.27 to 0.74).. Antibiotic prophylaxis in afebrile neutropenic patients significantly reduced all-cause mortality. In our review, the most significant reduction in mortality was observed in trials assessing prophylaxis with quinolones. The benefits of antibiotic prophylaxis outweighed the harm such as adverse effects and the development of resistance since all-cause mortality was reduced. As most trials in our review were of patients with haematologic cancer, we strongly recommend antibiotic prophylaxis for these patients, preferably with a quinolone. Prophylaxis may also be considered for patients with solid tumours or lymphoma.

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacteremia; Bacterial Infections; Cause of Death; Drug Resistance, Bacterial; Fever; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Neoplasms; Neutropenia; Quinolones; Randomized Controlled Trials as Topic; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii is an opportunistic pathogen causing life-threatening pneumonia in immunosuppressed patients. The number of non-HIV immunosuppressed patients at risk for Pneumocystis pneumonia is rapidly growing. In contrast to HIV patients, there are no guidelines for Pneumocystis prophylaxis in other immunocompromised hosts. A detailed analysis of current literature data allowed us hereby to define the type of immunocompromised patients for whom evidence suggests a benefit for PCP prophylaxis.

Topics: Anti-Infective Agents; Connective Tissue Diseases; Drug-Related Side Effects and Adverse Reactions; Evidence-Based Medicine; HIV Infections; Humans; Immunocompromised Host; Neoplasms; Pneumocystis carinii; Pneumonia, Pneumocystis; Practice Guidelines as Topic; Protein-Energy Malnutrition; Randomized Controlled Trials as Topic; Risk Factors; Transplantation; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Vasculitis

Bacterial infections are a major cause of morbidity and mortality in neutropenic patients following chemotherapy for malignancy. Trials have shown the efficacy of antibiotic prophylaxis in decreasing the incidence of bacterial infections, but not in reducing mortality rates.. This review aimed to evaluate whether antibiotic prophylaxis in afebrile neutropenic patients reduced mortality when compared to placebo or no intervention.. Electronic searches on The Cochrane Cancer Network Register of Trials (2004), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2004), MEDLINE (1966 to 2004) and EMBASE (1980 to 2004) and abstracts of conference proceedings; references of identified studies; the first author of each included trial was contacted.. RCTs or quasi-RCTs comparing different types of antibiotic prophylaxis with placebo or no intervention, or another antibiotic to prevent bacterial infections in afebrile neutropenic patients.. Two authors independently appraised the quality of each trial and extracted data from the included trials. Relative risks (RR) or average differences, with their 95% confidence intervals (CI) were estimated.. One hundred trials (10,274 patients) performed between the years 1973 to 2004 met inclusion criteria. Antibiotic prophylaxis significantly decreased the risk for death when compared with placebo or no intervention (RR, 0.66 [95% CI 0.54 to 0.81]). The authors estimated the number needed to treat (NNT) in order to prevent 1 death from all causes as 60 (95% CI 34 to 268). Prophylaxis resulted in a significant decrease in the risk of infection-related death, RR 0.58 (95% CI 0.45 to 0.74) and in the occurrence of fever, RR 0.78 (95% CI 0.75 to 0.82). A reduction in mortality was also evident when the more recently conducted quinolone trials were analysed separately. Quinolone prophylaxis reduced the risk for all-cause mortality, RR 0.52 (95% CI, 0.37 to 0.84).. Our review demonstrated that prophylaxis significantly reduced all-cause mortality. The most significant reduction in mortality was observed in trials assessing prophylaxis with quinolones. The benefit demonstrated in our review outweighs harm, such as adverse effects, and development of resistance, since all-cause mortality is reduced. Since most trials in our review were of patients with haematologic cancer, prophylaxis, preferably with a quinolone, should be considered for these patients.

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacterial Infections; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Neoplasms; Neutropenia; Quinolones; Randomized Controlled Trials as Topic; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii pneumonitis (PCP) is one of the most important opportunistic infections in children and adolescents with cancer. Its high frequency and a considerable mortality have led to primary chemoprophylaxis in patients with hematological malignancies and following allogeneic hematopoietic stem cell transplantation. Although less well characterized, patients with autologous stem cell transplantation and patients with dose-intensive chemotherapy for pediatric solid tumors may have a similarly high risk for PCP based on their profound T-cell depletion. For more than two decades, effective chemoprophylaxis for PCP has been available. Trimethoprim and sulfamethoxazole (TMP/SMX) is the prophylactic modality of first choice. The combination has been shown to be almost 100 % efficacious in pediatric cancer patients at highest risk, and it is usually well tolerated in this setting. Secondary alternatives to TMP/SMX include oral dapsone, oral atovaquone, and aerosolized pentamidine-isethionate. These modalities are less effective than TMP/SMX, and have been evaluated predominantly in HIV-infected patients. This article reviews epidemiology and current approaches to chemoprophylaxis for PCP in children and adolescents with cancer and/or hematopoietic stem cell transplantation, and provides evidence-based guidelines for indications and modalities of PCP prophylaxis in this population.

Topics: Adolescent; Age Factors; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Atovaquone; Child; Child, Preschool; Dapsone; Drug Therapy, Combination; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Infant; Naphthoquinones; Neoplasms; Odds Ratio; Pentamidine; Pneumonia, Pneumocystis; Practice Guidelines as Topic; Prospective Studies; Randomized Controlled Trials as Topic; Risk Factors; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

To perform a meta-analysis to estimate the efficacy of quinolone antibiotics in preventing infections, fevers, and deaths among cancer patients neutropenic following chemotherapy.. We searched MEDLINE to identify randomized trials of quinolone prophylaxis, controlled either with no prophylaxis or trimethoprim/sulfamethoxazole (TMS) prophylaxis. We pooled relative risks for outcomes using a random-effects model.. Eighteen trials with 1,408 subjects were included. Compared with no prophylaxis, quinolones significantly reduced the incidence of gram-negative bacterial infections (relative risk, 0.21; 95% confidence interval [CI], 0.12 to 0.37), microbiologically documented infections (0.65; 0.50 to 0.85), total infections (0.54; 0.31 to 0.95), and fevers (0.85; 0.73 to 0.99). Quinolone prophylaxis did not alter the incidence of gram-positive bacterial, fungal, or clinically documented infections, or infection-related deaths. Results were similar for trials that used TMS as the control regimen. Among those who received quinolones, the incidence of infections due to quinolone-resistant organisms was 3.0% (95% CI, 1.7% to 5.2%) for gram-negative species and 9.4% (95% CI, 5.3% to 16.3%) for gram-positive species. Based on limited data, the incidence of quinolone-resistant infections was not higher among quinolone recipients than controls. With fever as outcome, blinded trials found quinolones less efficacious than did unblinded trials.. Quinolone prophylaxis substantially reduces the incidence of various infection-related outcomes, but not deaths, in these patients. Although this reduction in infections may translate into a decrease in morbidity, the reduction in fevers (and by extension, use of empiric antibiotics) appears small, and blinded trials provided less evidence for benefit than unblinded trials. Quinolone-resistant infections are uncommon, but continued vigilance is warranted.

Topics: Anti-Infective Agents; Antineoplastic Agents; Fever; Humans; Neoplasms; Neutropenia; Opportunistic Infections; Quinolones; Randomized Controlled Trials as Topic; Risk; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii pneumonia (PCP) emerged in the 1980s as the most common opportunistic infection among patients with the acquired immunodeficiency syndrome (AIDS). Because of this, the presentation and clinical course of PCP has become well-known to many physicians. However, PCP continues to occur among patients not infected with the human immunodeficiency virus, generally those who receive immunosuppressive therapy as treatment for neoplastic disease. A review from Memorial Sloan-Kettering Cancer has shown that a new group of patients, those receiving corticosteroid therapy for brain neoplasm, are also at risk for the development of PCP and should receive PCP prophylaxis. Previously defined patient groups--people with acute lymphocytic leukemia or allogeneic bone marrow transplantation--also should continue to receive prophylaxis. In addition, the clinical course and outcome of patients with neoplastic disease who develop PCP may differ from those with AIDS and PCP: the disease may be much more fulminant among patients with neoplastic disease, and the mortality rate much higher, approaching 50% in the Memorial Sloan-Kettering Cancer Center series. Wider use of prophylaxis should decrease the frequency of this disease, whereas prompt initiation of therapy in patients with a compatible syndrome should help to improve mortality rates.

Topics: Humans; Immunocompromised Host; Immunosuppression Therapy; Neoplasms; Pneumonia, Pneumocystis; Prognosis; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Agranulocytosis; Anti-Infective Agents; Bacterial Infections; Child; Drug Combinations; Humans; Immune Tolerance; Neoplasms; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Agranulocytosis; Drug Combinations; Hematologic Diseases; Humans; Infection Control; Neoplasms; Patient Isolation; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Patients with malignant disease may be predisposed to bacterial infections because of neoplastic disruption of normal tissue barriers, exogenous immunosuppressive therapy (drugs with or without radiation), and intrinsic host immune deficits secondary to these diseases. Diminished polymorphonuclear leucocyte numbers or function and impaired humoral immunity are highly correlated with the development of serious bacterial infections. The usual signs and symptoms of infection may be absent or altered in a compromised host. Therapy must be instituted promptly upon clinical suspicion of bacterial infection, and empirical choices should usually include combinations that are synergistic for likely pathogens based on knowledge of the local predominant flora and susceptibility data. Synergism has most often been demonstrated in combinations that utilise a beta-lactam (semisynthetic penicillin or cephalosporin) and an aminoglycoside. Triple drug therapy has not been shown to be advantageous. Monotherapy with third generation cephalosporins, carbapenems, monobactams, or ureidopenicillins has not been proven to offer advantages over 2-drug regimens for these patients. Granulocytopenic patients who respond to 2-drug therapy but remain neutropenic may need continued treatment until the neutropenia subsides. Those who do not respond and remain febrile with an unclear focus may need to be started on antifungal therapy in addition to the antibacterial agent. The use of oral agents for the prophylaxis of neutropenic patients against bacteraemia remains controversial. If drugs are used, co-trimoxazole and nystatin suspension may be preferable.

Topics: Aminoglycosides; Anti-Bacterial Agents; Anti-Infective Agents; Antibody Formation; Bacterial Infections; Cephalosporins; Drug Combinations; Drug Hypersensitivity; Humans; Immunity, Cellular; Leukocyte Count; Neoplasms; Neutrophils; Penicillins; Risk; Sulfamethoxazole; Time Factors; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Agranulocytosis; Anti-Bacterial Agents; Bacterial Infections; Blood Transfusion; Clinical Trials as Topic; Drug Combinations; Environment, Controlled; Granulocytes; Humans; Neoplasms; Patient Isolation; Premedication; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Several prospectively randomized trials have shown that the administration of prophylactic oral nonabsorbable antibiotics may be beneficial in decreasing the incidence of infection in granulocytopenic patients, whereas others have not. Intolerable nausea and vomiting have prevented the prolonged use of these agents in some studies. Discontinuation of therapy while patients are still granulocytopenic has carried the risk of life-threatening infections, often with aminoglycoside-resistant gram-negative organisms. The benefit of selective decontamination with trimethoprim/sulfamethoxazole used prophylactically remains controversial. The use of trimethoprim/sulfamethoxazole may also be associated with the development of resistant, potentially pathogenic, organisms or prolonged neutropenia. These regimens do not appear to be indicated when patients are anticipated to be neutropenic for less than three weeks. Even in patients with prolonged neutropenia, the risks of such treatment must be weighed against potential benefits.

Topics: Acute Disease; Agranulocytosis; Anti-Bacterial Agents; Bacterial Infections; Clinical Trials as Topic; Colistin; Drug Combinations; Environment, Controlled; Gentamicins; Humans; Leukemia; Neoplasms; Nystatin; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

Infection is the major cause of morbidity and mortality in children receiving anticancer therapy. Children who have severe neutropenia (neutrophil count less than 100/mm3) for longer than 2 weeks should receive oral antibiotic prophylaxis. At present, trimethoprim sulfamethoxazole in combination with either nystatin or amphotericin B is the best regimen for reducing the incidence of serious infections. Trimethoprim sulfamethoxazole is very effective in the prevention of Pneumocystis carinii pneumonitis. Clinicans will have to balance the advantages and disadvantages of prophylaxis in patients who are at risk for P. carinii pneumonitis.

Topics: Adolescent; Adult; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Candidiasis; Child; Compliance; Drug Combinations; Humans; Leukemia; Neoplasms; Neutropenia; Nystatin; Pneumonia, Pneumocystis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Stenotrophomonas maltophilia infection is of concern in patients with cancer. Antibiotics active against S. maltophilia are rarely used in the treatment of febrile neutropenia, making it important to identify the factors influencing mortality in cancer patients with S. maltophilia infection. The objective of this study was to analyze the clinical characteristics and outcomes of cancer and hemopathic patients with S. maltophilia infection and assess the factors influencing the mortality. The microbiology laboratory records of Erciyes University, Faculty of Medicine Hospital were reviewed to retrospectively identify patients with S. maltophilia infection between January 2007 and June 2011. A total of 38 patients (25 male, 13 female) were eligible for the study. The median age of the patients was 53 years. The underlying disease was hematological malignancy and disorders in 76.3 % (29 cases), solid tumors in 15.8 % (six cases), aplastic anemia in 7.9 % (three cases), while 18.4 % (seven cases) were hematopoietic stem cell transplantation (HSCT) recipients. An indwelling central venous catheter was used in 32 cases (84.2 %). Twenty-seven patients (71.1 %) were neutropenic at the onset of infection. Nine patients (23.7 %) were receiving corticosteroid therapy. The overall 14-day mortality rate was 50 %. Three of the patients received empirical antibacterial treatment, and three HSCT recipients received trimethoprim-sulfamethoxazole prophylaxis, which is active against S. maltophilia. Severe sepsis (OR 13.24, 95 % confidence interval (CI) 1.62-108.57) and the duration of the treatment (OR 0.73, 95 % CI 0.60-0.90) were related to death based on logistic regression analysis findings. In immunocompromised hematology-oncology patients with severe sepsis, S. maltophilia should be considered as a possible cause of infection, and should be given effective empirical antibiotic treatment immediately; the antimicrobial spectrum may be narrowed according to results of antibiotic susceptibility test.

Topics: Adrenal Cortex Hormones; Adult; Aged; Anti-Infective Agents; Female; Gram-Negative Bacterial Infections; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Neoplasms; Neutropenia; Retrospective Studies; Sepsis; Severity of Illness Index; Stenotrophomonas maltophilia; Survival Rate; Time Factors; Transplantation, Homologous; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumonia due to Pneumocystis carinii is an infrequent complication following autologous stem cell transplantation (ASCT) which is associated with a high mortality. Although administration of trimethoprim/sulfa- methoxazole (TMP/SMX) is an effective prophylactic strategy for Pneumocystis carinii pneumonia (PCP), treatment-associated toxicity frequently results in discontinuation of therapy. We have conducted a prospective randomized trial comparing atovaquone, a new anti-Pneumocystis agent, with TMP/SMX for PCP prophylaxis following autologous peripheral blood stem cell (PBSC) transplantation. Thirty-nine patients were studied. Twenty patients received atovaquone suspension and 19 patients received TMP/SMX. The median ages were 44 (range 20-68) and 47 (range 32-63) years, respectively. A similar number of patients with solid tumors (14 vs 15) and hematologic malignancies (five vs five) were treated in each group. Either TMP/SMX (160/800 mg) or atovaquone (1500 mg) was administered daily from transplant day -5 until day -1, discontinued from day 0 to engraftment, then resumed 3 days per week until day +100 post-transplant. The median time to engraftment (ANC >0.5 x 109/l) was similar in both groups. Eighty percent of the patients randomized to atovaquone prophylaxis completed the study. Four atovaquone-treated patients were removed from study; two patients (10%) did not receive a transplant and two patients (10%) were removed due to a protocol violation. None of the 16 patients treated with atovaquone experienced treatment-associated adverse effects. Of the 19 patients randomized to receive TMP/SMX, 55% completed the study. Nine TMP/SMX-treated patients were removed from the study; one patient (5%) did not receive a transplant and eight patients (40%) were removed due to drug intolerance (P < 0.003). The rate of intolerance to TMP/SMX led to the early discontinuation of this randomized trial. Intolerance of TMP/SMX included elevated transaminase levels (n = 1), nausea or vomiting (n = 3), thrombocytopenia (n = 2) and neutropenia (n = 2). All episodes of TMP/SMP intolerance occurred following transplantation after a median duration of 17.5 (range 2-48) days and a median of 7 (range 1-20) doses. Resolution of adverse side-effects occurred in all eight patients within a median of 7 (range 2-20) days following discontinuation of therapy. Neither PCP nor bacterial infections were identified in any of the patients treated. This prospective randomized study demon

Topics: Adult; Aged; Antifungal Agents; Atovaquone; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppression Therapy; Male; Middle Aged; Naphthoquinones; Neoplasms; Pneumocystis; Pneumonia, Pneumocystis; Prospective Studies; Transplantation, Autologous; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

One hundred and eighteen (118) episodes of bacteremia and fungemia in children with cancer were compared to 401 episodes of bacteremia and fungemia in adults with cancer to assess differences in etiology, risk factors and outcome. A retrospective univariate analysis was performed of all episodes of bacteremia in national pediatric and adult cancer institutions appearing in 1990-1996. A total of 519 episodes of bacteremia were assessed and compared. Both cancer centers differed in prophylactic antibiotic policies. About 50% of adults but less than 5% of children received quinolone prophylaxis during neutropenia, even though the empiric antibiotic therapeutic strategy was similar. There were differences in etiology between the groups: staphylococci and Stenotrophomonas maltophilia were more frequently observed in children (P<0.01), Pseudomonas aeruginosa and Acinetobacter spp. in adults (P<0.05). Gram-positive bacteremia was surprisingly more commonly observed in adults (65.7% vs 33.3%, P<0.01). Mixed polymicrobial bacteremia occurred more commonly in adults (31.8% vs 7.6%, P<0.001) than in children. Analysis of risk factors did not observe differences in risk factors except for underlying disease (acute leukemia was more frequently observed in children -48.3% vs adults 33.7%, P<0.05 and prophylaxis: (prior prophylaxis with quinolones was more common in adults (47.5%) than in children (2.5%) P<0.0001). Overall and attributable mortality in pediatric bacteremia was significantly lower than in adults (P<0.03).

Topics: Adult; Analysis of Variance; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotic Prophylaxis; Antifungal Agents; Antineoplastic Agents; Bacteremia; Child; Colistin; Fluconazole; Fungemia; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Neoplasms; Neutropenia; Ofloxacin; Penicillin V; Penicillins; Retrospective Studies; Risk Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Twenty-four cancer patients with diffuse interstitial pneumonitis (DIP) were randomized to undergo an open lung biopsy (OLB) within 8 hours of presentation (12 patients) or to receive empiric antimicrobial therapy (ET) with trimethoprim-sulfamethoxazole (TMP-SMX) erythromycin for a minimum of 4 days (12 patients). Patients whose condition deteriorated underwent an OLB on day 4. Eight of 12 patients (67%) having OLB survived versus 10 of 12 (83%) receiving ET (P = .64). Morbidity occurred in nine of 12 (75%) having OLB versus eight of 12 (67%) receiving ET (P = 1.0). Concurrently, there were 14 additional cancer patients with DIP who were not randomized (nine refused, three had a coagulopathy contraindicating surgery, two were excluded by primary care physicians) and who were comparable demographically to the randomized group. Two received OLB and 12 ET. Combining the randomized and nonrandomized groups, eight of 14 (57%) having an initial OLB survived versus 18 of 24 (75%) of ET-treated patients (P2 = .19). Results of the OLB were seven Pneumocystis carinii pneumonia (PCP), five nonspecific pneumonitis (NSP), one cytomegalovirus, and one lymphoma. Results of OLB led to discontinuation of antibiotics in three patients. Of the 24 ET patients, eight failed to improve by day 4 and had an OLB. Results were two NSP, two PCP, two cancer, one blastomycosis, and one Candida pneumonia. Complications were seen in 10 of 14 (72%) initial OLB patients versus 14 of 24 (58%) patients on the ET arm (P = .65). When the complication rate between patients receiving only empiric antibiotics was compared with all patients having an OLB (initially or on day 4), the difference was greater in patients undergoing OLB (37% v 72%, respectively) (P2 = .14). ET with TMP-SMX plus erythromycin and broad spectrum antibiotics in granulocytopenic patients appeared to be as successful and potentially less toxic than an OLB in this study. Although the number of patients in this study was small, these data suggest that a trial of empiric antibiotic management may be reasonable in cancer patients presenting with DIP, especially if they are nonneutropenic.

Topics: Adult; Agranulocytosis; Biopsy; Diagnosis, Differential; Drug Therapy, Combination; Erythromycin; Female; Humans; Male; Middle Aged; Neoplasms; Pneumonia, Pneumocystis; Prospective Studies; Pulmonary Fibrosis; Random Allocation; Trimethoprim, Sulfamethoxazole Drug Combination

Eighty-four cancer patients at risk of infection because of neutropenia were randomized to receive nalidixic acid as an alternative to trimethoprim-sulfamethoxazole (TMP-SMX) for infection prophylaxis. Infections were documented significantly earlier and more often among patients who entered the trial with neutrophil counts of less than 0.1 X 10(9)/liter. TMP-SMX recipients experienced fewer microbiologically documented infections and bacteremias and were free of infection for a higher proportion of days with severe neutropenia (less than 0.1 X 10(9)/liter) than nalidixic acid recipients. Gram-negative bacillary and Staphylococcus aureus infections accounted for the major differences. Although the majority of aerobic gram-negative bacilli were eliminated from the feces after 1 week of prophylaxis with either agent, TMP-SMX was proved superior to nalidixic acid in this regard and was associated with acquired drug resistance by gram-negative bacilli less frequently. Both agents selected for colonization and subsequent infection by gram-positive cocci. Our data suggest that prophylaxis is most likely to be effective if administered to patients for at least 1 week before they become severely neutropenic. Nalidixic acid used as a single agent in doses of 4 g daily, however, cannot be recommended as an alternative to TMP-SMX for infection prophylaxis in neutropenic cancer patients.

Topics: Agranulocytosis; Antineoplastic Agents; Bacteria; Bacterial Infections; Clinical Trials as Topic; Drug Administration Schedule; Drug Combinations; Humans; Intestines; Microbial Sensitivity Tests; Mycoses; Nalidixic Acid; Neoplasms; Neutropenia; Random Allocation; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Agranulocytosis; Anti-Bacterial Agents; Bacterial Infections; Blood Transfusion; Clinical Trials as Topic; Drug Combinations; Environment, Controlled; Granulocytes; Humans; Neoplasms; Patient Isolation; Premedication; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Several prospectively randomized trials have shown that the administration of prophylactic oral nonabsorbable antibiotics may be beneficial in decreasing the incidence of infection in granulocytopenic patients, whereas others have not. Intolerable nausea and vomiting have prevented the prolonged use of these agents in some studies. Discontinuation of therapy while patients are still granulocytopenic has carried the risk of life-threatening infections, often with aminoglycoside-resistant gram-negative organisms. The benefit of selective decontamination with trimethoprim/sulfamethoxazole used prophylactically remains controversial. The use of trimethoprim/sulfamethoxazole may also be associated with the development of resistant, potentially pathogenic, organisms or prolonged neutropenia. These regimens do not appear to be indicated when patients are anticipated to be neutropenic for less than three weeks. Even in patients with prolonged neutropenia, the risks of such treatment must be weighed against potential benefits.

Topics: Acute Disease; Agranulocytosis; Anti-Bacterial Agents; Bacterial Infections; Clinical Trials as Topic; Colistin; Drug Combinations; Environment, Controlled; Gentamicins; Humans; Leukemia; Neoplasms; Nystatin; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

Ketoconazole or miconazole was randomly administered to 42 and 46 neutropenic patients respectively. Of the total number of stool cultures 12% were positive for yeasts in both groups; 4% of the total number of cultures from other sites (nose, throat, skin) were positive in both groups. Candida albicans was the most common isolate, but other fungal species were also identified. No patient developed fungemia; 5/88 patients developed severe oropharyngeal candidiasis while receiving prophylaxis. Among the 21 autopsies performed, 5 cases of pulmonary aspergillosis and 2 local and 1 disseminated candidiasis were demonstrated in 7 patients. Although there was no placebo group of patients in this study, post-mortem data suggest that miconazole or ketoconazole might reduce the incidence of disseminated candidiases in neutropenic patients.

Topics: Agranulocytosis; Antifungal Agents; Candidiasis; Drug Combinations; Female; Humans; Imidazoles; Ketoconazole; Male; Miconazole; Middle Aged; Mycoses; Neoplasms; Neutropenia; Piperazines; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

In an attempt to reduce the incidence of fever and infection, we randomized patients with cancer to receive trimethoprim/sulfamethoxazole plus erythromycin (TMP/SMX + E) versus placebos after each cycle of chemotherapy (no crossover) and to continue until granulocytopenia (polymorphonuclear leukocytes less than 500/mm3) resolved or the patient became febrile. We evaluated 541 episodes (150 patients); 249 episodes (77 patients) with TMP/SMX + E and 292 episodes (73 patients) with placebos. The patients' median age was 17 years. Thirty percent of the patients had leukemia, 23% had lymphoma, and 47% had solid tumors. Compliance with prescribed medication was prospectively rated as excellent in 60.6%, good in 11.7%, poor in 11.1%, and unknown in 16.6%; compliance was better for the placebo group (P = 0.001). The overall incidence of fever or infection was 22.1% for the TMP/SMX + E group versus 26.9% for the placebo group. When only episodes with excellent compliance in which granulocytopenia was documented were compared, the incidence of fever or infection was 18.1% for the TMP/SMX + E group vs 32.2% for the placebo group (P = 0.009), with bacterial infection occurring in 3.8% of the TMP/SMX + E group vs 11.9% of the placebo group (P = 0.019), and unexplained fever in 10.5% of the TMP/SMX + E group vs 19.6% of the placebo group (P = 0.037). Patients with good or poor compliance showed no significant benefit from the TMP/SMX + E, and patients with excellent compliance did best, regardless of whether they were receiving antibiotics or placebos, suggesting that patient compliance is an important independent variable. The incidence of fever or infection was significantly lower for patients with leukemia with excellent compliance who received antibiotics (P = 0.037) than for patients with lymphomas or solid tumors. Oral antibiotic prophylaxis reduced the incidence of fever and infection in some granulocytopenic patients, but the benefit was limited and restricted to patients whose compliance was complete.

Topics: Adolescent; Adult; Agranulocytosis; Bacterial Infections; Child; Child, Preschool; Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Erythromycin; Female; Fever; Humans; Infant; Leukemia; Lymphoma; Male; Neoplasms; Patient Compliance; Random Allocation; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Agranulocytosis; Anti-Bacterial Agents; Anti-Infective Agents; Bacterial Infections; Clinical Trials as Topic; Drug Combinations; Drug Therapy, Combination; Feces; Gentamicins; Humans; Neoplasms; Neutropenia; Pilot Projects; Random Allocation; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

A randomized study of intestinal decontamination was undertaken in 68 children with leukemia and solid tumours. Framycetin, colymycin, nystatin, and metronidazole were given in 35 neutropenic episodes in 33 children, while co-trimoxazole and lactobacilli preparation were administered in 35 episodes in 35 children. The diseases, severity of neutropenia, and incidence of infection at entry into study were comparable in the two groups. There was no significant difference in the incidence of infections developing during the phase of neutropenia. The median and range of time required to recover from neutropenia were also not different. Co-trimoxazole and lactobacilli were significantly better tolerated, there being no nausea and vomiting, no refusal to take medication, no dose reduction or change to an alternative regimen. We conclude that co-trimoxazole and lactobacilli preparation improve quality of life during a neutropenic episode and have the additional advantage of being relatively inexpensive.

Topics: Agranulocytosis; Anti-Bacterial Agents; Antifungal Agents; Bacterial Infections; Biological Products; Child; Child, Preschool; Colistin; Drug Combinations; Framycetin; Humans; Lactobacillus; Neoplasms; Neutropenia; Nystatin; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Serum creatinine-based estimated glomerular filtration rate (eGFRcr) may overestimate the glomerular filtration rate (GFR) in patients with cancer. Cystatin C-based eGFR (eGFRcys) is an alternative marker of GFR.. To determine whether the therapeutic drug levels and adverse events (AEs) associated with renally cleared medications were higher in patients with cancer whose eGFRcys was more than 30% lower than their eGFRcr.. This cohort study analyzed adult patients with cancer at 2 major academic cancer centers in Boston, Massachusetts. These patients had their creatinine and cystatin C measured on the same day between May 2010 and January 2022. The date of the first simultaneous eGFRcr and eGFRcys measurement was considered to be the baseline date.. The primary exposure was eGFR discordance, defined as an eGFRcys that was more than 30% lower than the eGFRcr.. The primary outcome was risk of the following medication-related AEs within 90 days of the baseline date: (1) supratherapeutic vancomycin trough level greater than 30 μg/mL, (2) trimethoprim-sulfamethoxazole-related hyperkalemia (>5.5 mEq/L), (3) baclofen toxic effect, and (4) supratherapeutic digoxin level (>2.0 ng/mL). For the secondary outcome, a multivariable Cox proportional hazards regression model was used to compare 30-day survival of those with vs without eGFR discordance.. A total of 1869 adult patients with cancer (mean [SD] age, 66 [14] years; 948 males [51%]) had simultaneous eGFRcys and eGFRcr measurement. There were 543 patients (29%) with an eGFRcys that was more than 30% lower than their eGFRcr. Patients with an eGFRcys that was more than 30% lower than their eGFRcr were more likely to experience medication-related AEs compared with patients with concordant eGFRs (defined as eGFRcys within 30% of eGFRcr), including vancomycin levels greater than 30 μg/mL (43 of 179 [24%] vs 7 of 77 [9%]; P = .01), trimethoprim-sulfamethoxazole-related hyperkalemia (29 of 129 [22%] vs 11 of 92 [12%]; P = .07), baclofen toxic effects (5 of 19 [26%] vs 0 of 11; P = .19), and supratherapeutic digoxin levels (7 of 24 [29%] vs 0 of 10; P = .08). The adjusted odds ratio for vancomycin levels more than 30 μg/mL was 2.59 (95% CI, 1.08-7.03; P = .04). Patients with an eGFRcys more than 30% lower than their eGFRcr had an increased 30-day mortality (adjusted hazard ratio, 1.98; 95% CI, 1.26-3.11; P = .003).. Results of this study suggest that among patients with cancer with simultaneous assessment of eGFRcys and eGFRcr, supratherapeutic drug levels and medication-related AEs occurred more commonly in those with an eGFRcys more than 30% lower than their eGFRcr. Future prospective studies are needed to improve and personalize GFR estimation and medication dosing in patients with cancer.

Topics: Adult; Aged; Baclofen; Cohort Studies; Creatinine; Cystatin C; Digoxin; Glomerular Filtration Rate; Humans; Hyperkalemia; Male; Neoplasms; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

Haemophagocytic lymphohistiocytosis (HLH) is an aggressive hyperinflammatory haematological condition often associated with malignancy, infection or rheumatological disorders. HLH has rarely been associated with medications, including antibiotics. We describe a case of a patient without significant medical history who presented with HLH following treatment with trimethoprim/sulfamethoxazole (TMP/SMX). Additionally, we will discuss the possible mechanism of medication-induced HLH as well as the successful use of dexamethasone as the sole treatment. Early diagnosis and treatment of this disease is critical and medication-induced HLH should be considered in cases without a clear aetiology. To our knowledge, this is the first case report of TMP/SMX-induced HLH that was successfully treated with steroid monotherapy and just the second case report of TMP/SMX-induced HLH.

Topics: Adult; Humans; Lymphohistiocytosis, Hemophagocytic; Neoplasms; Trimethoprim, Sulfamethoxazole Drug Combination

Prospective collection of clinical information for all suspected and proven cases of PJP in children with cancer in the UK and Ireland.. A surveillance survey was undertaken using a key contact at each paediatric oncology Principle Treatment Centre (PTC).. To describe the mortality, outcomes and use of prophylaxis in this at-risk group.. The study confirms that PJP is rare, with only 32 cases detected in the UK over a 2-year period reported from all 20 PTCs. No deaths were directly attributed to PJP, in contrast to previously reported high mortality rates. Breakthrough infection may occur despite prescription of ostensibly adequate prophylaxis with co-trimoxazole; 11 such cases were identified. Six infections occurred in patients for whom prophylaxis was not thought to be indicated. Two infections occurred in patients for whom prophylaxis was specifically omitted due to concerns about potential bone marrow suppression or delayed engraftment.. PJP in children treated for malignant disease is rare. Breakthrough infection despite prophylaxis with co-trimoxazole may represent pathogen resistance or non-compliance. Further consideration of the use of PJP prophylaxis during acute myeloid leukaemia and non-Hodgkin's lymphoma treatment is warranted, alongside appraisal of the clinical implications of the possible marrow suppressive effects of co-trimoxazole and its interactions with methotrexate.

Topics: Adolescent; Anti-Bacterial Agents; Antibiotic Prophylaxis; Antimetabolites, Antineoplastic; Child; Child, Preschool; Humans; Incidence; Infant; Ireland; Methotrexate; Neoplasms; Pneumocystis carinii; Pneumonia, Pneumocystis; Population Surveillance; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination; United Kingdom

Prophylaxis of Pneumocystis jiroveci pneumonia (PJP) with trimethoprim/sulfamethoxazole is a standard of care for children with hematologic malignancies, while its use in solid tumor patients is still debated. A retrospective study focusing on the use of PJP prophylaxis in patients with solid tumors was performed among 16 AIEOP centers: 1046/2863 patients did not receive prophylaxis and no cases of PJP were reported.

Topics: Adolescent; Anti-Bacterial Agents; Antibiotic Prophylaxis; Antineoplastic Agents; Child; Child, Preschool; Humans; Immunocompromised Host; Neoplasms; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Bacterial Agents; Cough; Diagnosis, Differential; Fever; Humans; Lung Neoplasms; Malaysia; Male; Melioidosis; Middle Aged; Neoplasms; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination; Weight Loss

Pneumocystis jirovecii pneumonia (PJP) is a life-threatening opportunistic infection. Prophylaxis is recommended for patients with malignancies and trimethoprim-sulfamethoxazole (TMP-SMX) is the recommended first-line agent. Many paediatric patients receive second-line agents due to perceived adverse reactions from TMP-SMX.. The objective of the study is to determine the risk of PJP in patients receiving TMP-SMX vs. second-line medications for prophylaxis.. We conducted a retrospective, single centre, case-control study of paediatric oncology patients. Cases included children diagnosed with PJP by microscopy between 2000 and 2018 while being treated for a malignancy. Controls were matched by age, oncologic diagnosis, treatment protocol, phase of treatment and oncologic diagnosis date. For each case, up to 5 controls were randomly selected. The index date was the date of the PJP diagnosis for cases and the equivalent dummy date for controls.. Eleven cases with PJP were identified and matched with 50 controls. Six (55%) cases and 42 (84%) controls were on prophylaxis with TMP-SMX. The remaining patients received inhaled pentamidine (3 cases, 4 controls), dapsone (2 cases, 3 controls), or atovaquone (1 control). Myelosuppression was the most common reason to stop TMP-SMX. Cases with PJP were less likely to have been taking TMP-SMX in the 3 months before diagnosis when compared with controls (odds ratio: 0.15, 95% confidence interval: 0.01-0.97, p = 0.02).. TMP-SMX prophylaxis was associated with a lower risk of developing PJP compared with second-line treatments. Although alternate agents may be required in certain situations, efforts should be made to rechallenge with TMP-SMX when possible.

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Case-Control Studies; Child; Child, Preschool; Female; Humans; Infant; Male; Neoplasms; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Disease-Free Survival; Female; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Minocycline; Neoplasms; Retrospective Studies; Risk Factors; Stenotrophomonas maltophilia; Survival Rate; Tertiary Care Centers; Trimethoprim, Sulfamethoxazole Drug Combination

Nocardiosis has historically been reported in immunocompromised patients, but Australian epidemiological and antimicrobial susceptibility data are limited.. To describe the epidemiology, diagnosis and initial treatment of nocardiosis in an Australian tertiary hospital over 7 years.. In this retrospective study, all positive cultures for Nocardia species from any site isolated at the Alfred Hospital, Melbourne, between 1 January 2010 and 31 December 2016 were identified, and corresponding laboratory data and medical records reviewed.. Sixty-eight non-duplicate isolates were identified from 67 patients. Common predisposing factors were chronic lung disease (38/67; 57%), organ, particularly lung, transplantation (13/67; 19%) and solid organ malignancy (6/67; 9%); 12% (8/67) of patients had no identifiable systemic risk factors. Seventy-nine percent (53/67) of patients had pulmonary nocardiosis only. Nocardia nova was the most commonly isolated species (20/68; 29%). In 48% (32/67) of patients, Nocardia species were isolated only on specific mycobacterial media. All tested species were susceptible to sulfamethoxazole-trimethoprim and amikacin, with the majority (58/63; 92%) susceptible to imipenem. All-cause mortality rates at 6 and 12 months where data were available were 15% (10/66 patients) and 22% (14/64 patients) respectively.. In the largest Australian series in 25 years, nocardiosis predominantly affected patients with chronic lung disease or impaired cell-mediated immunity. A significant proportion of organisms from pulmonary sites were isolated on mycobacterial culture media only, suggesting that its use may improve yield. Isolates remain highly susceptible to sulfamethoxazole-trimethoprim, amikacin and imipenem, while other agents should be used only after confirmation of in vitro susceptibility.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Australia; Female; Humans; Lung Diseases; Male; Middle Aged; Neoplasms; Nocardia; Nocardia Infections; Retrospective Studies; Risk Factors; Tertiary Care Centers; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

The aim of this study was to describe the clinical characteristics and antimicrobial patterns of Stenotrophomonas maltophilia bloodstream infections (BSI) and pneumonia episodes in patients with cancer.. Patients with S. maltophilia BSI or pneumonia admitted from 1 Jan. 2000 to 31 Dec. 2016 were identified at the Instituto Nacional de Cancerología (INCan), a tertiary-care oncology hospital in Mexico City.. During the study period, there were 171 isolates identified. The mean age of the whole group was 46.9 ± 17.4 years; 99 (57.9%) were women. There were 95 BSI: 64 ambulatory catheter-related BSI (CRBSI), 20 nosocomial CRBSI, and 11 secondary BSI. Mortality was higher in nosocomial CRBSI (40%) vs. that in ambulatory CRBSI (7.8%) (p = 0.001). There were 76 pneumonia episodes; all were nosocomial acquired; 46 (60.5%) ventilator-associated. From all the group, nine strains (5.2%) were resistant to sulfamethoxazole/trimethoprim/(SMX/TMP). At the first month, 54 patients (31.6%) have died, 38 due to pneumonia (70%) and 16 due to BSI (30%, p < 0.001). Multivariate analysis showed that removal of central venous catheter was associated with a favorable outcome in patients with bacteremia. For patients with pneumonia, age ≥ 65 years and inappropriate antimicrobial treatment were risk factors associated with 30-day mortality.. S. maltophilia related with ambulatory CRBSI have a better prognosis than other sources of BSI. Older patients with pneumonia who do not receive appropriate antibiotics have higher mortality. SMX/TMP is still the antibiotic of choice.

Topics: Adult; Aged; Anti-Bacterial Agents; Anti-Infective Agents; Female; Gram-Negative Bacterial Infections; Hospitalization; Humans; Male; Mexico; Middle Aged; Mortality; Neoplasms; Pneumonia; Prognosis; Risk Factors; Stenotrophomonas maltophilia; Tertiary Care Centers; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis Jirovecii (PJ) is regarded as an agent of fungal infection and in cases of pneumocystis pneumonia (PCP) in immune-compromised patients including cancer patients. It is not clear what kinds of cancer, treatments, and environment need prophylaxis for PCP. In this study, we have analyzed the detectability of PJ DNA from sputum, and discussed prophylaxis and risk factors regarding PCP.. A total of forty-nine materials (twenty-four from outpatients during cancer chemotherapies and twenty-five from healthy control subjects) was collected. Their PJ DNAs were amplified using nested PCR with specific primers of the PJ gene (the mitochondrial small subunit rRNA gene).. PJ DNA was detectable in 46% of specimens (sputum) from cancer patients during chemotherapies, and incidences of not significantly different among types of cancer and chemotherapy regimens. Prophylactic use of Sulfamethoxazole/Trimetoprim (ST) reduced the detection of PJ DNA. Detection of PJ DNA is not high among healthy non-smokers (20%) and high among healthy smokers (47%).. Prophylactic use of ST may be necessary for cancer patients during chemotherapies. Also, smoking may be associated with PJ colonization in the airway and air vesicles, and may increase the mortality rate for PCP. All patients undergoing cancer chemotherapies should cease smoking.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Bronchoalveolar Lavage Fluid; DNA Primers; DNA, Fungal; Female; Genes, rRNA; Healthy Volunteers; Humans; Immunocompromised Host; Male; Middle Aged; Neoplasms; Outpatients; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Respiratory System; Smokers; Sputum; Trimethoprim, Sulfamethoxazole Drug Combination

Nocardiosis is a rare disease with polymorphic presentations. The epidemiology and clinical presentation could change with the increasing number of immunocompromised patients.. The medical records and microbiological data of patients affected by nocardiosis and treated at the university hospitals of Marseille between 2004 and 2014 were analyzed retrospectively.. The cases of 34 patients infected by Nocardia spp during this period were analyzed. The main underlying conditions were transplantation (n=15), malignancy (n=9), cystic fibrosis (n=4), and immune disease (n=3); no immunodeficiency condition was observed for three patients. No case of AIDS was observed. At diagnosis, 61.8% had received steroids for over 3 months. Four clinical presentations were identified, depending on the underlying condition: the disseminated form (50.0%) and the visceral isolated form (26.5%) in severely immunocompromised patients, the bronchial form (14.7%) in patients with chronic lung disease, and the cutaneous isolated form (8.8%) in immunocompetent patients. Nocardia farcinica was the main species identified (26.5%). Trimethoprim-sulfamethoxazole was prescribed in 68.0% of patients, and 38.0% underwent surgery. Mortality was 11.7%, and the patients who died had disseminated or visceral nocardiosis.. The clinical presentation and outcome of nocardiosis depend on the patient's initial immune status and underlying pulmonary condition. Severe forms were all iatrogenic, occurring after treatments altering the immune system.

Topics: Adult; Aged; Chronic Disease; Cystic Fibrosis; Female; France; History, 21st Century; Hospitals, University; Humans; Immunocompromised Host; Male; Medical Records; Middle Aged; Neoplasms; Nocardia; Nocardia Infections; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

The aim of this study was to evaluate the in vitro effects and clinical efficacies of trimethoprim-sulfamethoxazole (SXT) combined with other antimicrobial agents against Stenotrophomonas maltophilia.. In vitro analysis was conducted on 89 S. maltophilia strains isolated from blood and the respiratory tract between June 2012 and October 2014. Levofloxacin (LVX), ticarcillin-clavulanic acid (TIM), and minocycline (MIN) were selected for an examination of their effects when individually combined with SXT by the checkerboard method. In addition, 29 S. maltophilia bacteremia cases were reviewed and the clinical efficacies of SXT-based combination therapies were analyzed.. SXT+LVX showed synergy in 21, no interactions in 61, and antagonism in 7. SXT+TIM showed synergy in 71, and no interactions in 18. SXT+MIN showed synergy in 10, and no interactions in 79. The review of clinical data indicated that a combination of SXT+fluoroquinolone was not associated with improved prognosis compared with monotherapy.. The in vitro data indicated that SXT+TIM had beneficial microbiological effects and was not antagonistic. Our in vitro and clinical data analyses do not support the routine use of SXT+fluoroquinolone combination therapy for S. maltophilia infection.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Clavulanic Acids; Drug Therapy, Combination; Female; Fluoroquinolones; Gram-Negative Bacterial Infections; Humans; Levofloxacin; Male; Middle Aged; Minocycline; Neoplasms; Stenotrophomonas maltophilia; Ticarcillin; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Although it is well-established that children undergoing allogeneic stem cell transplants and treatment for leukemia should be offered prophylaxis against Pneumocystis jirovecii pneumonia, the risk for children with solid malignancies is less certain. This guideline has been developed with the aim of standardizing practice and optimizing the benefit versus risk of prophylactic medication in this group of patients. P. jirovecii pneumonia has a high mortality rate even with prompt antimicrobial treatment. Since prophylaxis with co-trimoxazole is safe, effective, and inexpensive, we suggest that all children with malignancies undergoing immunosuppressive therapy are offered prophylaxis unless there are clear contraindications.

Topics: Antibiotic Prophylaxis; Child; Humans; Neoplasms; Pneumocystis carinii; Pneumonia, Pneumocystis; Practice Guidelines as Topic; Trimethoprim, Sulfamethoxazole Drug Combination

Patients with cancer, particularly those with hematologic malignancies, are at an increased risk of invasive pneumococcal disease (IPD) and they are included in the list of subjects for whom pneumococcal vaccination is recommended. The main aim of this study was to evaluate Streptococcus pneumoniae colonization in school-aged children and adolescents with cancer to determine the potential protective efficacy of 13-valent pneumococcal conjugate vaccine (PCV13). An oropharyngeal swab was obtained from 277 patients (age range 6-17 years) with cancer during routine clinical visits and analyzed for S. pneumoniae using real-time polymerase chain reaction. S. pneumoniae was identified in 52 patients (18.8%), including 47/235 (20.0%) with hematologic malignancies and 5/42 (11.9%) with solid tumors. Colonization declined significantly with an increase in age (odds ratio [OR] 0.34, 95% confidence interval [CI] 0.16-0.71, and OR 0.30, 95% CI 0.11-0.82 in children aged 10-14 and ≥15 years, respectively, as compared to those <10 years). Carriage was more common among patients with leukemia or lymphoma than in children with solid tumors. Co-trimoxazole prophylaxis was significantly associated with reduced pneumococcal carriage (OR 0.41, 95% CI 0.19-0.89). A total of 15/58 (25.9%) and 26/216 (12.0%) children were colonized by PCV13 serotypes among cancer patients previously vaccinated and not vaccinated with 7-valent pneumococcal conjugate vaccine (PCV7), respectively. In conclusion, this study indicates that children and adolescents with cancer are frequently colonized by S. pneumoniae. Because most of the carried serotypes are included in PCV13, this vaccine is presently the best solution to reduce the risk of IPD in these patients.

Topics: Adolescent; Carrier State; Child; DNA, Bacterial; Female; Heptavalent Pneumococcal Conjugate Vaccine; Humans; Male; Nasopharynx; Neoplasms; Pneumococcal Infections; Pneumococcal Vaccines; Real-Time Polymerase Chain Reaction; Serogroup; Streptococcus pneumoniae; Trimethoprim, Sulfamethoxazole Drug Combination; Vaccination; Vaccines, Conjugate

Dalbavancin is a long acting, bactericidal lipoglycopeptide. Its in vitro activity was compared with that of vancomycin, daptomycin, linezolid, trimethoprim/sulfamethoxazole (TMP/SMX) and levofloxacin against 241 Gram-positive organisms isolated from cancer patients. The rank order of potency for the glycopeptides based on MIC90 (μg ml(-1)), that is, the concentration of antimicrobial agent required to inhibit 90% of isolates tested was dalbavancin (0.12 μg ml(-1))>daptomycin (1.0 μg ml(-1))>vancomycin (2.0 μg ml(-1)) for coagulase-negative staphylococci and Staphylococcus aureus isolates (including methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) strains). Dalbavancin had potent activity against staphylococcal isolates with vancomycin MICs⩾1.0 μg ml(-1). TMP/SMX also had potent activity against staphylococci including methicillin-resistant strains, whereas levofloxacin had moderate to poor anti-staphylococcal activity. Dalbavancin also exhibited more potent activity than vancomycin and daptomycin against Bacillus spp., Corynebacterium spp., Micrococcus spp. and various streptococci (including Streptococcus pneumoniae, viridans group streptococci (VGS), beta-hemolytic streptococci and gamma-hemolytic streptococci). MBC determinations showed that dalbavancin had potent bactericidal activity against MRSA with no tolerance being detected. These data suggest that dalbavancin may be considered as an alternative to vancomycin, especially in institutions wherein a substantial proportion of infections are caused by organisms with vancomycin MICs⩾1.0 μg ml(-1).

Topics: Anti-Bacterial Agents; Daptomycin; Gram-Positive Bacteria; Humans; Levofloxacin; Linezolid; Microbial Sensitivity Tests; Neoplasms; Teicoplanin; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

Central venous catheters, often needed by cancer patients, can be the source of Nocardia bacteremia. We evaluated the clinical characteristics and outcomes of 17 cancer patients with Nocardia bacteremia. For 10 patients, the bacteremia was associated with the catheter; for the other 7, it was a disseminated infection. N. nova complex was the leading cause of bacteremia. Nocardia promoted heavy biofilm formation on the surface of central venous catheter segments tested in an in vitro biofilm model. Trimethoprim- and minocycline-based lock solutions had potent in vitro activity against biofilm growth. Patients with Nocardia central venous catheter-associated bloodstream infections responded well to catheter removal and antimicrobial drug therapy, whereas those with disseminated bacteremia had poor prognoses.

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactams; Biofilms; Catheterization, Central Venous; Catheters, Indwelling; Drug Therapy, Combination; Female; Humans; Male; Microscopy, Electron, Scanning; Neoplasms; Nocardia Infections; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

The aim of this study is to describe clinical characteristics and outcome of Burkholderia cepacia bacteraemia, susceptibility of the isolates and differences between cases from epidemic outbreaks and sporadic cases.. From 1993 to 2009, episodes of B. cepacia bacteraemia were prospectively collected in a university hospital.. A total of 33 episodes were included, of which 21 were part of two outbreaks (9 in 1994 and 12 in 2006). Outbreak cases had a median age of 58 years, 45% had neoplasia, median length of stay until bacteraemia was 15 d (range 0-120) and 82% had received an antibiotic. The most prevalent sources of bacteraemia were catheter (48%) and unknown (33%). On the other hand, sporadic cases stayed longer until diagnosis (median 25 days versus 11, p=0.041) and showed a trend to have neoplasia more frequently (83% versus 33%, p=0.083). Susceptibility to antibiotics was varied and co-trimoxazole was the only active agent against all strains.. B. cepacia is an uncommon pathogen, which affects patients with prolonged hospitalization and severe comorbidities. The identification of more than one case in a short term of time should raise the suspicion of an outbreak.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Burkholderia cepacia; Burkholderia Infections; Epidemics; Female; Hospitals, University; Humans; Length of Stay; Male; Microbial Sensitivity Tests; Middle Aged; Neoplasms; Prospective Studies; Sex Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

The clinical features of pneumocystis pneumonia (PCP) differ according to the predisposing factors responsible for immunosuppression. Although PCP in patients with acquired immunodeficiency syndrome (AIDS) has been extensively described, its characteristics in non-AIDS patients, such as those with malignancies, are not thoroughly documented.. To characterize and compare the clinical and imaging features of PCP in patients with malignancies with those in AIDS patients.. A multi-center retrospective study.. We evaluated the clinical and radiological features of PCP in 21 patients with malignancies and in 17 with AIDS. Clinical presentation, serum markers, oxygenation, CT findings, and outcome were examined.. The patients with malignancies showed shorter durations of symptoms before PCP was diagnosed. The levels of serum markers and the oxygenation index did not differ. CT showed diffuse or widespread ground-glass opacity (GGO) in all of the patients evaluated. None of the AIDS patients demonstrated consolidation, whereas half of the patients with malignancy showed consolidation along with GGO. The extent of GGO scored on CT images was significantly greater in the AIDS patients. No correlation was observed between the CT findings and other clinical parameters. All of the AIDS patients recovered from PCP, whereas six patients with malignancies died within a month after the onset of PCP.. The characteristics of the CT images differed between the patient groups with different underlying disorders, although it remains to be determined whether CT findings are associated with other clinical features or are predictive of the outcome of PCP.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Biomarkers; Female; Humans; Leukocyte Count; Male; Middle Aged; Neoplasms; Oxygen; Pneumonia, Pneumocystis; Retrospective Studies; Tomography, X-Ray Computed; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

In order to evaluate the incidence rate and possible risk factors associated with AIDS-related malignancies and infections (ARMI) we performed data analysis of clinical charts of HIV patients in two hospital cohorts, that started high activity antiretroviral therapy (HAART) between July 2003 and October 2007. Trimethoprim-sulfamethoxazole and Azithromycin prophylaxis was provided according to current guidelines. We evaluated development of ARMI six months after-starting HAART and its association with clinical and epidemiological variables. Of 235 patients analyzed -118 women (50.2%) and 117 men (49.8%)- 11 presented ARMI: 3 pulmonary TB and 3 lymph nodes TB cases, 3 cases with meningeal Cryptococcus, one Chagas's disease presenting brain mass and one with non-Hodgkin lymphoma. ARMI incidence: 4.7%. A CD4 cell count < 100/150 was associated with risk of developing ARMI. The mean CD4 cell count was 73 in patients who developed ARMI and 143 in those who did not. No association was found with the other analyzed variables. In the CD4 cell count < 150 group one out of 4 patients with reactive serology presented Chagas's disease causing brain mass; none of the 46 patients with reactive serology presented toxoplasmosis encephalitis. The incidence rate of ARMI was 4.7%. TB in first place and cryptococcosis in second were the AIDS events more frequently observed. A low CD4 cell count was the only observed risk factor statistically associated with development of ARMI. The role of prophylaxis in this population should be re-evaluated.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Antiretroviral Therapy, Highly Active; Argentina; Azithromycin; CD4 Lymphocyte Count; Female; Humans; Male; Neoplasms; Odds Ratio; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Viral Load

Nocardia species is an uncommon pathogen that affects both immunosuppressed and immunocompetent patients. The clinical and microbiologic spectrum of nocardiosis has changed recently due to the widespread use of cotrimoxazole prophylaxis, the emergence of new types of immunosuppressed patients, and the improved identification of isolates using molecular techniques. Nocardia asteroides was traditionally considered the predominant organism, and prophylaxis with cotrimoxazole was considered almost universally protective. We conducted the current study to determine the incidence of nocardiosis and its microbiologic and clinical characteristics in a general hospital over the last 12 years. We reviewed the clinical records of all patients in whom Nocardia species was isolated from clinical specimens between 1995 and 2006. Nocardia isolates were identified by standard procedures and by 5' end 16S rRNA gene polymerase chain reaction (PCR) and sequencing. Susceptibility to cotrimoxazole, minocycline, imipenem, linezolid, and amikacin was determined by the broth microdilution method following the guidelines of the Clinical and Laboratory Standards Institute.The incidence of Nocardia infections did not increase significantly during the study period (0.39/100,000 inhabitants in 1995-1998 and 0.55/100,000 inhabitants in 2003-2006). Nocardia was recovered from 43 patients. Six were considered to be colonized. The colonizing species were N. farcinica, N. nova, and N. asteroides. All colonized patients had severe underlying pulmonary conditions and were treated with antimicrobials (6 patients) or corticosteroids (4 patients). Invasive nocardiosis was diagnosed in 37 patients (86.5% were men, and their mean age was 55.8 +/- 17.3 yr). The most common underlying condition in our institution was human immunodeficiency virus (HIV) infection (10 patients; 27%), followed by chronic obstructive pulmonary disease (8 patients; 21.6%), autoimmune diseases (8 patients; 21.6%), solid organ transplantation (7 patients; 18.9%), and cancer (4 patients; 10.8%). The most important risk factor for nocardiosis was corticosteroid administration (23 patients; 62.2%). Nocardiosis affected the lungs in 26 cases (70.3%), the skin in 3 cases (8.1%), and the central nervous system in 2 cases (5.4%). It was disseminated in 5 cases (13.5%) and caused otomastoiditis in 1 (2.7%). The species identified were N. cyriacigeorgica (32.4%), N. farcinica (24.3%), N. otitidiscaviarum (10.8%), N. veterana (8.1%

Topics: Adult; Aged; Anti-Infective Agents; Autoimmune Diseases; Drug Resistance, Bacterial; Female; HIV Infections; Humans; Incidence; Male; Middle Aged; Neoplasms; Nocardia; Nocardia Infections; Organ Transplantation; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; Risk Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Infections are significant causes of morbidity and mortality among immunocompromised patients, but little is known about the adherence by the paediatric cancer patients to preventive anti-infective interventions.. A voluntary and anonymised questionnaire was distributed to all patients, completing intensive anticancer therapy. Compliance was analysed by using a panel of eight commonly recommended preventive interventions and semi-quantitative scoring of adherence by the patient and/or its caretaker. Satisfaction with information and belief in the efficacy of the interventions were similarly assessed. Relationships of these factors to compliance were explored by using an overall compliance score and non-parametric correlation and/or ANOVA and logistic regression, respectively.. In 216 children and adolescents (mean age: 8 years; 94 girls) included in the study, compliance rates were the highest for food restriction (89.3%), the use of topic antimycotics (88.2%) and trimethoprim/sulfamethoxazole (86.6%), and the lowest for the use of face masks (68.8%), antiseptic mouth rinses (67.1%), non-absorbable antibiotic agents (66.5%) and restrictions in social contacts (65.5%). The most frequent reasons for drug non-compliance were forgetfulness and patient refusal. Compliance correlated with haematological malignancy, younger age and belief in its efficacy, but not with the perceived degree of information, burden of interventions and overall satisfaction with quality of information and medical care.. Compliance to recommended anti-infective prophylactic interventions was variable and correlated with haematological malignancy, younger age and belief in efficacy.

Topics: Adolescent; Adult; Analysis of Variance; Anti-Infective Agents; Anti-Infective Agents, Local; Antifungal Agents; Child; Child, Preschool; Cost of Illness; Female; Humans; Infant; Infection Control; Male; Neoplasms; Patient Compliance; Patient Satisfaction; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Pneumocystis jirovecii pneumonia is an opportunistic infection capable of causing life-threatening pneumonia in immunocompromised patients. To elucidate the clinical presentation and outcome of this disease in Taiwan, we analyzed the patients with P. jirovecii pneumonia during a 34-month period.. We collected data retrospectively from patients with P. jirovecii pneumonia at a medical center in northern Taiwan between January 2004 and October 2006. The diagnosis was made by nested polymerase chain reaction (PCR) analysis of expectorated sputum. Demographics, clinical characteristics, laboratory findings, and outcomes were compared between patients with and without human immunodeficiency virus (HIV) infection.. Forty nine patients were included in this study. The most common underlying diseases were HIV and malignancies. The mean (+/- standard deviation) age of the 49 patients was 54 +/- 20.2 years (range, 5 to 96 years). The mean CD4+ T-lymphocyte count was 110 cells/microL (range, 0-670 cells/microL). Although the mean CD4+ T-lymphocyte count of the non-HIV group was higher than that of the HIV group (165 +/- 78 cells/microL vs 57.5 +/- 97 cells/microL), statistical significance was not obtained (p=0.087). Arterial oxygenation (ratio of arterial oxygenation to fraction of inspired oxygen) was less than 200 mm Hg in 28 patients. Lactate dehydrogenase levels were higher than the normal range in 15 patients. A significantly higher proportion of patients died in the group without HIV compared with the HIV-infected patients (17/34 [50.0%] vs 1/15 [6.7%]; p=0.004).. P. jirovecii pneumonia remains a significant problem for immunocompromised patients. The mortality rate for patients without HIV infection was high (50%). Greater alertness with regard to early detection of P. jirovecii in HIV-negative immunosuppressed patients with the application of nested PCR may improve the clinical management and outcome.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; AIDS-Related Opportunistic Infections; Analysis of Variance; Anti-Infective Agents; Chi-Square Distribution; Child; Child, Preschool; Female; HIV Infections; Humans; Immunocompromised Host; Male; Middle Aged; Neoplasms; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Retrospective Studies; Sputum; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis pneumonia (PCP) is a serious complication of chemotherapy-induced immunosuppression. Trimethoprim-sulfamethoxazole (TMP-SMZ) given twice daily, 3 days every week is considered the best form of prophylaxis for PCP. We evaluated PCP prophylaxis in all children up to 18 years of age undergoing cancer chemotherapy over a 2-year period. Four children were diagnosed with PCP over 24 months. Two of 12 children on intravenous pentamidine, 1 of 143 on TMP-SMZ and 1 of 36 on dapsone for PCP prophylaxis developed PCP. Intravenous pentamidine may not be as effective as previously considered and should be used with caution.

Topics: Adolescent; Adult; Anti-Infective Agents; Antibiotic Prophylaxis; Antineoplastic Agents; Child; Child, Preschool; Female; Humans; Immunocompromised Host; Infant; Infusions, Intravenous; Male; Neoplasms; Opportunistic Infections; Pentamidine; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii, formerly carinii, pneumonia (PCP) poses a life-threatening risk to oncology patients. The use of trimethoprim-sulfamethoxazole (TMP-SMZ) prophylaxis virtually eliminates the risk of infection; however, many patients cannot tolerate TMP-SMZ. We performed a retrospective analysis to determine the PCP breakthrough rate in pediatric oncology patients receiving intravenous pentamidine as second line PCP prophylaxis.. We conducted a retrospective chart review of pediatric oncology patients who received intravenous pentamidine from 2001 to 2006 at our institution. The diagnosis, age and bone marrow transplant (BMT) status were determined. A subset of patients had review of their records to determine the justification for discontinuing TMP-SMZ. Children who developed symptoms of pneumonia with a clinical suspicion of PCP underwent bronchoscopy, allowing for identification of Pneumocystis.. A total of 232 patients received 1,706 doses of intravenous pentamidine and no toxicities were identified. The main reasons for discontinuing TMP-SMZ were bone marrow suppression and drug allergy. Three children developed PCP, equating to a breakthrough rate of 1.3%. Two of these children had undergone BMT (1.9% breakthrough rate) and both were under the age of two (6.5% breakthrough rate).. The use of intravenous pentamidine as PCP prophylaxis results in a breakthrough rate of 1.3%. TMP-SMZ is the first choice for PCP prophylaxis. However, when necessary, the use of intravenous pentamidine has an acceptably low failure rate, even in high-risk BMT patients. Other options should be considered for children less than 2 years of age.

Topics: Antifungal Agents; Bone Marrow Transplantation; Child; Child, Preschool; Humans; Immunocompromised Host; Infant; Injections, Intravenous; Neoplasms; Pentamidine; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Stenotrophomonas maltophilia is responsible for an increasing number of infections, especially in hospitalized patients. Therapy options are limited and trimethoprim/sulfamethoxazole (TMP/SMX) is often the main treatment option for this infection. In the current study, the risk factors were determined for the emergence of multidrug-resistant (MDR) S. maltophilia.. A case-control study was conducted to determine risk factors for the development of MDR S. maltophilia in cancer patients. The case group was composed of patients treated at the University of Texas M. D. Anderson Cancer Center for MDR S. maltophilia between 1996 and 2004 (n = 54). Two control groups were used: patients at comparable risk for S. maltophilia (C-controls) and patients with S. maltophilia infection that was susceptible to TMP-SMX and at least 2 other antibiotics (ciprofloxacin, ceftazidime, amikacin, and ticarcillin/clavulanate) (S-controls).. When compared with C-controls, prior use of carbapenems or quinolones and admission to an intensive care unit within 30 days of isolation of the pathogen were found to be independently associated with MDR S. maltophilia infection (P < .02), as was an increased overall mortality rate (P = .04). When compared with S-controls, risk factors were history of S. maltophilia infection during the prior year and prior use of TMP-SMX (P = .015).. Judicious use of TMP-SMX, carbapenems, and quinolones is necessary to control the risk for MDR S. maltophilia infection.

Topics: Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Case-Control Studies; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Neoplasms; Retrospective Studies; Risk Factors; Stenotrophomonas maltophilia; Trimethoprim, Sulfamethoxazole Drug Combination

Stenotrophomonas maltophilia, a multidrug resistant Gram-negative pathogen, has become a more frequent cause of bloodstream infections (BSI). Little is known about development of S. maltophilia bacteremia in children. The objective of this study was to define risk factors and outcomes associated with S. maltophilia BSI in children.. This was a retrospective case-control study conducted at The Children's Hospital of Philadelphia between January 1, 2000 and July 31, 2005. All patients with S. maltophilia BSI were compared with a random sample of patients with non-Stenotrophomonas Gram-negative rod BSI.. Fifty-one cases and 103 control subjects were included in the study. The median patient age was 2 years (interquartile range: 1 day-8.5 years). Patients with S. maltophilia BSI were significantly more likely to have a malignancy and be coinfected with other organisms than those with other Gram-negative rod infections. On multivariate analysis, patients with S. maltophilia BSI were more likely to develop their infection in the home setting (adjusted OR, 4.18; 95% CI: 1.44-12.16; P = 0.009). Additionally, prior exposure to trimethoprim-sulfamethoxazole, receipt of steroids or other immunosuppressive medication in the 30 days preceding infection and black race were associated with the development of S. maltophilia BSI.. Patients with Stenotrophomonas maltophilia BSI are more likely to have a polymicrobial infection and develop their infection in the home setting compared with patients with BSI caused by other Gram-negative rods.

Topics: Bacteremia; Black or African American; Case-Control Studies; Child; Child, Preschool; Female; Gram-Negative Bacterial Infections; Humans; Immunosuppressive Agents; Infant; Infant, Newborn; Male; Multivariate Analysis; Neoplasms; Philadelphia; Retrospective Studies; Risk Factors; Stenotrophomonas maltophilia; Steroids; Trimethoprim, Sulfamethoxazole Drug Combination

Stenotrophomonas maltophilia bacteremia is an important cause of mortality among immunocompromised children. However, there has been little information concerning S. maltophilia bacteremia in the pediatric population.. We reviewed the drug susceptibility of bloodstream isolates of S. maltophilia and medical charts of S. maltophilia bacteremia patients less than 18 years old at the Department of Pediatrics, National Taiwan University Hospital from January 1993 to June 2003. The risk factors associated with mortality of the patients with S. maltophilia bacteremia were analyzed.. In total, 32 episodes (31 patients) of S. maltophilia bacteremia were reviewed. The average rate of nosocomial bloodstream infection was 8.3 episodes per 100,000 patient-days, and an average of 6.4% of them were caused by S. maltophilia. Malignancy was the most common underlying disease (32%). Six episodes of S. maltophilia bacteremia had soft tissue involvement, and only 1 of them underwent surgical intervention and survived. These 32 isolates were most susceptible to trimethoprim-sulfamethoxazole (91%), and no obvious increase in multidrug resistance was noted in the previous 10 years. The crude mortality rate was 40.6%. Malignancy, failure to remove central venous catheter, and ineffective antibiotic treatment were significant risk factors for mortality.. Early and effective antimicrobial therapy and removal of central venous catheter as soon as possible are vital for the successful management of S. maltophilia bacteremia.

Topics: Adolescent; Anti-Bacterial Agents; Bacteremia; Catheterization, Central Venous; Child; Child, Preschool; Female; Gram-Negative Bacterial Infections; Hospitals, University; Humans; Incidence; Infant; Male; Microbial Sensitivity Tests; Neoplasms; Risk Factors; Stenotrophomonas maltophilia; Taiwan; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jiroveci pneumonia is a common infection in patients with AIDS but an infrequent cause of pneumonia in cancer patients. Little is known about the impact of cancer type and hematopoietic stem cell transplantation on the presentation and outcome of P. jiroveci pneumonia in cancer patients. A retrospective cohort study of all patients with cancer and P. jiroveci pneumonia cared for at The M.D. Anderson Cancer Center during 1990-2003 was conducted. Eighty episodes of P. jiroveci pneumonia in 79 patients were identified. In most (67%) episodes, patients had a hematologic malignancy. In 23 (29%) episodes, patients had undergone hematopoietic stem cell transplantation. Twenty-seven percent of patients with histopathologically confirmed P. jiroveci pneumonia had nodular infiltrates on the radiographic study. Pleural effusion and pneumothorax were more common in patients with hematopoietic stem cell transplantation than in those with solid tumors. Clinical suspicion of P. jiroveci pneumonia was less common in patients with nodular infiltrates than in those without such a radiographic finding (7 vs. 39%; p=0.002). Twenty-six of 76 (34%) patients with data available died of P. jiroveci pneumonia. Predictors of death by univariate analysis included older age, tachypnea, high APACHE II score, use of mechanical ventilation or vasopressors, lower arterial pH level, absence of interstitial component, pneumothorax, and comorbid conditions (all p<0.05). Multivariate analysis identified the use of mechanical ventilation as an independent predictor of death. Death attributable to P. jiroveci pneumonia appeared to be higher in patients with hematopoietic stem cell transplantation. The clinical presentation of P. jiroveci pneumonia in cancer patients may be affected by the category of cancer and the history of hematopoietic stem cell transplantation. P. jiroveci pneumonia remains a rare yet severe infection in cancer patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analysis of Variance; Anti-Infective Agents; Antineoplastic Combined Chemotherapy Protocols; Child; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Neoplasms; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Antibiotic Prophylaxis; Female; Follow-Up Studies; Hematologic Neoplasms; Humans; Immunocompromised Host; Male; Neoplasms; Pneumocystis carinii; Pneumonia, Pneumocystis; Probability; Registries; Retrospective Studies; Risk Assessment; Survival Rate; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Mycobacterium vaccae is a rapidly growing mycobacterial species that was previously not considered a human pathogen. We report four cases of M. vaccae infection that occurred in the southern United States; one patient had cutaneous disease, and three patients had cavitary lung disease. Two of the three patients with pulmonary disease had a history of exposure to cattle. The conditions of all patients improved with therapy: the cutaneous infection responded to therapy with minocycline and trimethoprim-sulfamethoxazole, and the pulmonary infections responded to therapy with ciprofloxacin.

Topics: Aged; Animals; Anti-Bacterial Agents; Cattle; Ciprofloxacin; Humans; Male; Middle Aged; Minocycline; Mycobacterium; Mycobacterium Infections; Neoplasms; Pneumonia, Bacterial; Skin Diseases, Bacterial; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adolescent; Child; Humans; Neoplasms; Pentamidine; Pneumonia, Pneumocystis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim/sulfamethoxazole (TMP/SMX) is the drug of choice for Pneumocystis carinii pneumonia (PCP) prophylaxis in immunocompromised patients. In children with malignancy, TMP/SMX is well tolerated, but adverse reactions that necessitate discontinuation can occur. We evaluated the safety and efficacy of aerosolized pentamidine (AP) as an alternative prophylaxis modality in children with malignancy who are intolerant of or allergic to TMP/SMX.. AP (200 mg/m2 every 4 weeks) was administered to 60 children with malignancy receiving chemotherapy who had experienced severe adverse reactions to TMP/SMX. Seven hundred twenty doses of AP have been administered during a 3 1/2-year period (21,600 patient-days), with 30 patients treated for > or = 12 months (range, 12 to 25).. Adverse reactions occurred during 79 (10%) of the 720 treatments and included bronchospasm in 23, cough in 40, vomiting in 10, and nausea in six. Only two patients had severe bronchospasm. AP was discontinued due to toxicity in three patients (5%). None of the patients (upper 95% confidence limit, 0.049) have developed PCP.. AP appears to be well tolerated and effective in the prevention of PCP in children with malignancy.

Topics: Adolescent; Aerosols; Child; Child, Preschool; Drug Hypersensitivity; Female; Humans; Male; Neoplasms; Opportunistic Infections; Pentamidine; Pneumonia, Pneumocystis; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

We studied episodes of fever and neutropenia in children and adolescents without documented infections to determine the risk of recurrent fever after early discontinuation of empiric antibiotic therapy; 213 episodes occurred in 106 patients. All patients received empiric antibiotic therapy after cultures were obtained. Antibiotic therapy was discontinued if no infection was found, culture results were negative for 48 hours, and the patient was afebrile for 24 hours. In 83 episodes without documented infection, antibiotic therapy was stopped with absolute neutrophil counts < 0.5 x 10(9)/L (< 500/mm3); 50 episodes occurred in patients with solid tumors, leukemia in remission, and other hematologic conditions (group 1), and 33 in patients with active leukemia (group 2). Fever recurred before neutropenia resolved in 6% of group 1 and 45% of group 2 episodes; five patients in group 2 had documented infection. Recurrent fever risk correlated with absolute neutrophil count and monocyte count at the time antibiotic therapy was stopped, in both groups, as did increasing absolute neutrophil count and increasing leukocyte count in group 2. We conclude that discontinuing antibiotic therapy is safe in febrile episodes without documented infections before neutropenia resolves in patients with high potential for bone marrow recovery. The risk of recurrent fever and infection is significant for patients with neutropenia and poor marrow recovery potential.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Child; Child, Preschool; Drug Therapy, Combination; Female; Fever of Unknown Origin; Humans; Infant; Infusions, Intravenous; Leukemia; Male; Neoplasms; Neutropenia; Recurrence; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

We conducted a survey over a 21-year period of the incidence and risk of occurrence of episodes of pneumonia and pneumonitis in children treated for solid tumours and leukaemia. One hundred episodes occurred amongst 219 patients, seven of which were associated with death. Focal opacification on the chest radiograph was more common than diffuse opacification. Patients with leukaemia had a significantly higher rate of occurrence of pneumonia and pneumonitis during the periods of induction and maintenance compared with the off-treatment period, and during the relapse period compared with the period of maintenance. Patients with solid tumours had a significantly higher rate of occurrence during treatment compared to the off-treatment period. The rate of occurrence on treatment was the same in patients with solid tumours and acute leukaemia. Children with malignancy have a high incidence of pneumonia and pneumonitis and death is rare if the patient does not have terminal malignant disease.

Topics: Acute Disease; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Bacterial Infections; Child; Clinical Protocols; Daunorubicin; Humans; Immunocompromised Host; Leukemia; Methotrexate; Neoplasms; Opportunistic Infections; Pneumonia; Pneumonia, Viral; Prednisolone; Prednisone; Trimethoprim, Sulfamethoxazole Drug Combination; Vincristine

Topics: Acquired Immunodeficiency Syndrome; Adult; Allied Health Personnel; Anti-Infective Agents; Child; Cross Infection; Drugs, Investigational; Female; HIV-1; Humans; Infections; Male; Neoplasms; Pneumonia, Pneumocystis; Sarcoma, Kaposi; Substance-Related Disorders; Trimethoprim, Sulfamethoxazole Drug Combination; United States; Viral Vaccines

The in vitro activity of cefpodoxime, an oral cephalosporin ester, against 792 bacterial isolates representing 36 species was evaluated in comparison to that of ciprofloxacin and trimethoprim/sulfamethoxazole (TMP/SMX). Cefpodoxime inhibited the majority of Streptococcus spp., Haemophilus influenzae and Proteus mirabilis at a concentration of less than or equal to 0.12 microgram/ml. It was also active against Citrobacter diversus, Escherichia coli, Klebsiella spp., Proteus vulgaris, Serratia marcescens and methicillin-susceptible Staphylococcus aureus isolates. Overall, cefpodoxime appeared to be less active than ciprofloxacin and TMP/SMX against many pathogens common in cancer patients.

Topics: Bacteria; Bacterial Infections; Cefpodoxime; Ceftizoxime; Ciprofloxacin; Humans; Microbial Sensitivity Tests; Neoplasms; Trimethoprim, Sulfamethoxazole Drug Combination

At the M.D. Anderson Cancer Center (Houston), Listeria monocytogenes was cultured from 14 patients between 1980 and 1987. The case records of 11 of these patients were reviewed. Underlying malignancies included acute leukemia (three), lymphoma (two), myeloma (one), adenocarcinoma of colon (two), carcinoma of breast (one), carcinoma of lung (one), and Kaposi's sarcoma associated with the acquired immune deficiency syndrome (one). Listeria monocytogenes was cultured from blood (eight patients), cerebrospinal fluid (CSF) (two patients), and from both blood and CSF in one patient. All patients were receiving immunosuppressive therapy including corticosteroids in seven. An absolute neutrophil count of less than 1000/mm3 was noted in five. Bacteremia was the predominant type of infection and ten patients responded to antimicrobial therapy.

Topics: Adult; Aged; Ampicillin; Female; Humans; Immunosuppressive Agents; Listeriosis; Male; Meningitis, Listeria; Middle Aged; Neoplasms; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

Topics: Anti-Infective Agents; Drug Combinations; Drug Hypersensitivity; Humans; Hypersensitivity, Immediate; Immunoglobulin E; Immunologic Deficiency Syndromes; Neoplasms; Reagins; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Between 1976 and 1983, 53 cases of Pneumocystis carinii pneumonia were documented at the Mayo Clinic. Underlying diseases included leukemia in 15 patients, lymphoma in nine, nonhematologic malignancies in five, acquired immune deficiency syndrome in two, an various inflammatory diseases treated by corticosteroids in 16 patients. Cytotoxic drugs with corticosteroids were used in 68 percent of patients, whereas 23 percent received corticosteroids alone. Clinical features consisted of progressive dyspnea (74 percent), cough (55 percent), and fever (62 percent), with normal findings on examination (43 percent), or crackles (53 percent). Arterial oxygen tension and oxygen saturation were 48.6 +/- 12.8 mm Hg and 81.2 +/- 6.5 percent, respectively. Chest roentgenographs exhibited diffuse alveolar and interstitial infiltrates with predominantly perihilar distribution. The diagnostic rates for open lung biopsy and bronchoscopy were 97 percent and 62 percent, respectively. Clinical improvement and survival following appropriate therapy were noted in 22 patients (41.5 percent), whereas the remaining 31 patients died within four weeks of hospitalization. When survivors were compared with nonsurvivors, there was no difference in mean age, leukocyte counts, arterial oxygen tension, or duration of symptoms before treatment. A coexisting pulmonary infection was identified more frequently in nonsurvivors (51.6 percent) than in survivors (22.7 percent, p = 0.01). The mortality from P. carinii pneumonia alone was 47 percent, whereas 76 percent of those with coexisting infection died. Despite antibiotic therapy and potentially effective chemoprophylaxis, P. carinii pneumonia remains a significant and life-threatening complication of diseases or treatments associated with immune suppression.

Topics: Acquired Immunodeficiency Syndrome; Adrenal Cortex Hormones; Drug Combinations; Female; Humans; Leukemia; Lymphoma; Male; Middle Aged; Neoplasms; Pentamidine; Pneumonia, Pneumocystis; Retrospective Studies; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

By a study of 87 oncologic hospitalized patients, affected by serious infectious complications and treated with high-dose antibiotic therapy including co-trimoxazole, the authors evaluate the allergic and immunologic reactions to the drug on clinical and serological basis and try to outline the pathogenic implicated mechanisms.

Topics: Anti-Infective Agents; Complement Activation; Drug Combinations; Drug Hypersensitivity; Hospitalization; Humans; Immunoglobulin E; Neoplasms; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Viral infections are one of the major complications after bone marrow transplantation, with high mortality and morbidity. Fourty-six patients between 3 and 48 years old (median 15 years) received orally 400 mg (under age 6, 200 mg) acyclovir 4 times daily from day -12 before to day 84 after BMT. All patients were isolated in laminar-airflow units for at least 23 days with total enteral decontamination. They were concomitantly treated with anti-CMV-hyperimmunoglobulin and cotrimoxazol. During acyclovir prophylaxis seven patients had herpes simplex virus infections, all of them were seropositive before BMT. Acyclovir plasma concentrations were measured by use of a new HPLC method. No acyclovir was present (detection limit 40 ng/ml) in the plasma of five out of six patients with HSV infections. Three of them had non-compliance, and a lack of acyclovir absorption developed in two patients under conditioning regimen. No drug-related side effects were observed. Laboratory tests did not show liver or renal toxicity. Take and hematologic reconstitution were unchanged. In our study, oral acyclovir reduced the incidence of herpes simplex infections after bone marrow transplantation. Herpes infections only occurred in patients with non-compliance or lack of acyclovir absorption.

Topics: Acyclovir; Administration, Oral; Adolescent; Adult; Bone Marrow Transplantation; Child; Child, Preschool; Chromatography, High Pressure Liquid; Cytomegalovirus Infections; Drug Combinations; Drug Therapy, Combination; gamma-Globulins; Herpesviridae Infections; Humans; Immune Tolerance; Infant; Neoplasms; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Bacterial Infections; Child; Drug Combinations; Drug Evaluation; Drug Resistance, Microbial; Gram-Negative Bacteria; Humans; Neoplasms; Premedication; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Rapidly progressive pulmonary distress occurs as a secondary complication in immunocompromised pediatric patients. These patients usually develop a pattern of diffuse alveolar and/or interstitial infiltrates on chest x-ray and pursue a rapidly downhill course despite intensive respiratory support with the use of multiple and varied antimicrobial regimens. These patients are subjected to diagnostic open lung biopsies to establish a diagnosis. The diagnostic value of open lung biopsy and its current impact on therapy is not clearly established. This retrospective study attempts to determine the impact of open lung biopsy on diagnosis and therapeutic outcome. Between November, 1974, and October, 1982, 40 diagnostic open lung biopsies were performed on immunocompromised patients with clinically progressive respiratory disease. Adequate follow-up for complete evaluation was possible in 34 of these patients. Most of these patients had hematologic malignancies and all were on chemotherapeutic drugs at time of open lung biopsy. Open lung biopsy was considered helpful, ie, resulted in a change in antimicrobial therapy or substantiated preoperative therapy, in 17 of our 34 patients (50%). A "treatable" condition, amenable to antimicrobial therapy, was diagnosed in 16 of our patients (47%). Pneumocystis carinii pneumonitis (PCP) was the most common diagnosis in 11 (69%) of our "treatable" patients. The remaining five "treatable" patients had sarcoidosis (1), histiocytosis X (1), bacterial pneumonitis (1) and fungal pneumonitis (2). No diagnosis was achieved by open lung biopsy in ten (30%) of our patients. There were two complications attributable to open lung biopsy (6%), including one death. All PCP patients treated with trimethoprim sulfamethoxazole (T/S) survived.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Biopsy; Child; Child, Preschool; Drug Combinations; Female; Humans; Immunosuppression Therapy; Infant; Leukemia; Lung; Male; Neoplasms; Pneumonia, Pneumocystis; Pneumonia, Viral; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination