Two treatment failures using diethylstibestrol in treatment of coccidioidomycosis.
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Coccidioidomycosis↗
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Treatment failures in patients with ventilator-associated pneumonia.
Treatment failures in patients with VAP are a complex issue and form a major challenge for clinicians. The following key elements inherent to a rational approach to treatment failures have been elucidated: (1) the presence of treatment failure must be thoroughly defined and assessed; (2) the many causes behind treatment failures must be realized, particularly the possibility of pneumonia-related and extrapulmonary reasons; (3) the recognition of different patterns of treatment failures as a useful framework for decisions about modalities and intensity of diagnostic reassessment; and (4) the establishment of a protocol for the search of pulmonary and extrapulmonary sites of infection and noninfectious causes of nonresponse. Only such a rational approach precludes the adverse effects of blind empiricism, which always implies a dangerous and costly overtreatment. Many issues related to treatment failures remain unsettled, and efforts will have to be made in the future to improve current clinical attitudes to treatment failures in VAP.
Anti-Bacterial Agents↗
Open label, multicenter study of gatifloxacin treatment of recurrent otitis media and acute otitis media treatment failure.
BACKGROUND: Recurrent otitis media and treatment failures of acute infections are refractory to therapy. Newer fluoroquinolones have excellent activity against respiratory pathogens, but their use in children has been limited because of concerns about adverse effects. METHODS: This was an open label, multicenter trial in which patients with recurrent otitis media or acute otitis media (AOM) treatment failure were treated with 10 mg/kg gatifloxacin oral suspension once daily for 10 days. Before treatment a tympanocentesis or a swab of middle ear fluid was obtained. Nasopharyngeal swabs were obtained at baseline and at the end of therapy. Efficacy was evaluated 3 to 10 days after cessation of treatment and at 3 to 4 weeks. Safety monitoring included special attention to any sign or symptom suggestive of joint or bone abnormality. RESULTS: The study enrolled 254 patients 6 months to 7 years of age, with one-half (52%) of the patients having recurrent otitis media, 17% having AOM treatment failure and 28% having both. Cure was achieved posttreatment in 88% of 198 clinically evaluable patients, with similar outcomes for patients younger or older than 2 years of age. Of the 45 evaluable patients with Streptococcus pneumoniae, 38 (84%) were cured, including 25 of 28 with penicillin-nonsusceptible strains. Also cured were 89% of those with Haemophilus influenzae and those with Moraxella catarrhalis. No selection of resistance to gatifloxacin was detected among nasopharyngeal pathogens. Eighty-three percent of the children had sustained cure at the 4 weeks follow-up visit. Adverse events were primarily mild gastrointestinal, with no occurrences of arthropathy. CONCLUSION: Gatifloxacin is safe and effective for treatment of recurrent otitis media and AOM treatment failure in children.
Acute Disease↗
The phenomenon of treatment failures in Human African Trypanosomiasis.
Treatment of Human African Trypanosomiasis (HAT or sleeping sickness) relies on a few drugs which are old, toxic and expensive. The most important drug for the treatment of second stage infection is melarsoprol. During the last 50 years treatment failures with melarsoprol were not a major problem in Trypanosoma brucei gambiense patients. Commonly a relapse rate of 5-8% was reported, but in recent years it has increased dramatically in some important foci of T. b. gambiense sleeping sickness. Treatment failures for T. b. rhodesiense are much less of a problem apart from some reports between 1960 and 1985 of refractoriness in T. b. rhodesiense patients in East Africa. Analysis of those isolates revealed that their in vitro sensitivity to melarsoprol was one-tenth that of sensitive isolates, and complete failure to cure the infection in the acute mouse model with melarsoprol levels comparable with those in human patients. There was very little indication of resistance in T. b. gambiense isolates from Côte d'Ivoire and NW Uganda. The in vitro melarsoprol sensitivities for populations from relapsing and from curable patients were in the same range. Melarsoprol concentrations in the plasma and cerebrospinal fluid of patients 24 h after treatment did not show any difference between patients who relapsed and those who could be cured. The reason for relapses in the recent T. b. gambiense epidemics are not known. Other parasite-related factors might be involved, e.g. affinity to extravascular sites other than the CNS which are less accessible to the drug. In conclusion, a combination of factors rather than a single one may be responsible for the phenomenon of melarsoprol treatment failures in T. b. gambiense patients.
Africa, Eastern↗
Gene delivery approaches to heart failure treatment.
Heart failure remains a leading cause of worldwide morbidity and mortality. Despite recent advances in treatment and our increasing knowledge of pathophysiology and the molecular derangements involved in the failing heart, our ability to affect the underlying cardiac disease processes is limited. In recent years, there has been considerable interest in myocardial gene transfer as both an investigational and potential therapeutic modality. Ultimately, the goal of any such strategy is to reprogramme failing cardiac myocytes and correct the aberrant molecular events causing heart failure. So far, viral vectors have been utilised with success more frequently than any other method of gene delivery in animal models. Studies in animal models and in failing human cardiomyocytes in culture targeting specific molecular pathways, including the beta-adrenergic receptor cascade and the myocyte intracellular calcium handling system, have shown encouraging results and offer hope that gene manipulation may provide novel adjunctive therapeutic modalities for human heart failure.
Adenoviridae↗
Predictors of treatment failure during highly active antiretroviral therapy (racing trial).
PURPOSE: To determine factors associated with virological failure during long-term treatment with the triple combination of saquinavir soft gel capsule, zalcitabine and zidovudine. METHOD: Open-label, prospective, multicentre study undertaken in private practices and the outpatient department of the Auguste-Viktoria-Hospital. A total of 95 patients with plasma HIV RNA > 5000 copies/ml who had received no more than 6 months pre-treatment with NRTIs and no prior PI therapy received saquinavir soft gel, zalcitabine and zidovudine for 52 weeks, before being randomly assigned to either remain on therapy or switch to nelfinavir, lamivudine and zidovudine for further 52 weeks. RESULTS: Combination therapy with saquinavir, zalcitabine and zidovudine was found to be effective and well tolerated, with virological response to therapy maintained for up to 2 years. In patients responding to therapy, switching to a novel triple regimen did not result in a virological or immunological worsening, but it did not confer an additional clinical benefit. Factors predictive of early treatment failure (virological failure within 16 weeks of treatment initiation) included high viral load and presence of RT mutations at baseline (OR: 0.30, 95% CI 0.11 0.83 and OR 0.13, 95% CI 0.03 0.52, respectively), with baseline viral load and the development of genotypic mutations on therapy being predictive of late treatment failure (16 52 weeks; OR: 0.15, 95% 0.05 0.46 and OR: 0.26, 95% CI < 0.001 1.16, respectively). Plasma saquinavir concentration < 50 mg/ml at 4 weeks was also found to be an independent risk factor for both early and late treatment failure (OR: 1.80, 95% CI 1.23 2.64 and OR: 1.16, 95% CI 0.84 1.60, respectively). CONCLUSIONS: While antiretroviral drug resistance appears to be a principal cause of treatment failure, other factors such as inadequate drug plasma concentrations also play a role.
Adult↗
Lack of association of Staphylococcus aureus type A beta-lactamase with cefazolin combined with antimicrobial spacer placement prosthetic joint infection treatment failure.
Association of cefazolin treatment failure with type A beta-lactamase-producing Staphylococcus aureus has been suggested. The prevalence of beta-lactamase gene types among 23 methicillin-susceptible S. aureus (MSSA) isolates associated with prosthetic joint infection (PJI) treated with cefazolin was determined using polymerase chain reaction (PCR), and clinical and microbiologic outcomes were assessed. PCR revealed 4 isolates without blaZ, and 12 with type A, 2 with type B, and 5 with type C blaZ. Of 13 patients undergoing resection arthroplasty with subsequent reimplantation, all received antimicrobial spacer placement at resection with or without antimicrobial-impregnated polymethylmethacrylate at reimplantation. All 13 cases had tissue cultures at time of reimplantation that were negative for S. aureus and 11 had histopathology specimens showing no acute inflammation. Of 8 type A cases undergoing reimplantation, all prostheses remained in place at follow-up (median, 798 days; range, 32-927 days). We conclude that type A blaZ is common in MSSA PJI and that cefazolin therapy for blaZ MSSA PJI can be successful when combined with 2-stage reimplantation and local antimicrobial therapy.
Anti-Bacterial Agents↗
In vitro cell culture systems as the basis for an extracorporeal blood purification strategy in multiorgan failure treatment.
Multiorgan failure (MOF) based on septic processes is very common but prognostically an extremely severe disease that has to be treated exclusively under intensive care conditions. Extracorporeal blood purification (ECBP) using specific and efficient systems such as the microspheres based detoxification system (MDS) (Artif Organs 1996;20:420) could improve significantly the situation of MOF in terms of the efficient removal of endotoxins as well as key mediators such as tumor necrosis factor alpha (TNF alpha). The purpose of the study was to test the effectiveness of endotoxin and cytokine removal to blunt cellular response. In terms of the in vitro principle methodology, isolated peripheral blood mononuclear cells (PBMC) were incubated with endotoxins and a selective endotoxin adsorbent, which was added at various times (immediately or 30, 60, 120, 240, or 360 min) after the onset of incubation. TNF alpha release of monocytes was measured following a standard procedure after 20 h. Human TNF alpha was incubated with cultured human endothelial cells with and without a specific TNF alpha adsorbent (polyclonal antibodies coated on polystyrene particles). The results showed that after the initial addition of endotoxins, the activation of monocytes can be stopped within 120 min by addition of endotoxin adsorbents. In addition, specific TNF alpha adsorbents are able to prevent intercellular adhesion molecule 1 (ICAM-1) expression of endothelial cells, therefore avoiding activation of endothelial cells. In conclusion, cell culture models are suitable to simulate cell interaction in MOF. Specific adsorbents are able to reduce or block pathophysiologically relevant cell interactions, and the time frame for effective ECBP seems to be very short, and therefore, efficiency must be high.
Cells, Cultured↗
Azithromycin compared with beta-lactam antibiotic treatment failures in pneumococcal infections of children.
OBJECTIVE: To determine whether treatment failures occurred more commonly with azithromycin than with beta-lactam antibiotics in children who developed invasive pneumococcal disease within 30 days of receiving prior antimicrobial therapy. METHODS: Retrospective review of medical records of children evaluated at Texas Children's Hospital between 1996 and 2002 who had received antimicrobials (azithromycin or a beta-lactam antibiotic) and developed invasive pneumococcal disease within 30 days. Treatment failure was defined as invasive pneumococcal infection that occurred while taking antimicrobials or within 3 days of stopping azithromycin treatment or 1 day of stopping beta-lactam treatment. Penicillin and azithromycin susceptibilities were determined and categorized according to National Committee for Clinical Laboratory Standards guidelines. RESULTS: We identified 21 and 33 children with similar demographic features who had developed invasive pneumococcal disease within 1 month of receiving azithromycin or a beta-lactam antibiotic, respectively. Eleven (52%) children in the azithromycin group and 11 (33%) in the beta-lactam group met the definition for treatment failures (P = 0.34). Eight treatment failures while receiving azithromycin were caused by pneumococci with the macrolide-resistant (M) phenotype, 2 with the macrolide-, lincosamide- and streptogramin B-resistant (MLSB) phenotype and 1 by a macrolide-susceptible organism. In the beta-lactam group 7 had a penicillin-resistant isolate, 3 had an intermediately susceptible isolate and 1 had a susceptible isolate. CONCLUSIONS: Our study suggests that treatment failures among patients who developed invasive disease within 30 days of receiving an antimicrobial occur as frequently in patients who receive beta-lactam antibiotics as in those who receive azithromycin. Furthermore macrolide resistant organisms are not more likely to be recovered after a macrolide treatment failure than a penicillin-nonsusceptible isolate being recovered after a beta-lactam treatment failure (P = 1.0).
Anti-Bacterial Agents↗
Reactions to infertility based on extent of treatment failure.
OBJECTIVE: To examine the relationship between amount of treatment failure and personal and marital distress. DESIGN: In this cross-sectional design, three groups of women (n = 91) with varying amounts of treatment failure experience were compared on measures of general and infertility-related distress and marital and sexual distress. RESULTS: The relationship between treatment failure experience and personal and marital distress was found to be curvilinear. The group that had a moderate amount of treatment failure experienced the most distress whereas the distress level of those without or with a high amount of treatment failure experience was comparable. The results also showed that the relationship between amount of treatment failure and distress was independent of age, years infertile, or years in treatment. CONCLUSION: The findings of this study provide support for infertility theories that suggest that infertility is a process rather than a series of independent emotional events and suggest that the distress women experience during infertility is a necessary part of their evolution toward acceptance of their infertility.
Adult↗
Assessment of different treatment failure criteria in a cohort of relapsing-remitting multiple sclerosis patients treated with interferon beta: implications for clinical trials.
Clinical trials with interferons in relapsing-remitting multiple sclerosis have shown a modest effect on disability using fixed definitions of treatment failure to measure disease progression. However, in the course of the disease, treatment failure may be influenced by interrater variability and frequent remissions. Thus, the purpose of this study was to assess the clinical usefulness of different treatment failure criteria in a cohort of relapsing-remitting multiple sclerosis patients treated with interferon beta. We studied 252 patients with a follow-up of more than 2 years. We used four different criteria of treatment failure with increasing stringency (1 Expanded Disability Status Scale [EDSS] point increase confirmed at 3 months, 1 EDSS point increase confirmed at 6 months, 1.5 EDSS points increase confirmed at 3 months, and 1.5 EDSS points increase confirmed at 6 months). We divided treatment failure into permanent treatment failure and transient treatment failure. We considered permanent treatment failure when treatment failure was confirmed on the last two scheduled visits and transient treatment failure when treatment failure was not confirmed on these visits at different time points (9, 12, 18, and 24 months). We calculated the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the different criteria of treatment failure to identify patients who achieved a high degree of disability after 4 years of follow-up. Regardless of the stringency of treatment failure definitions, a variable proportion of patients with treatment failure had transient treatment failure depending on the criterion applied. Patients with transient treatment failure had a significantly lower EDSS at entry compared with those with permanent treatment failure or no treatment failure. The number of relapses in patients with transient treatment failure did not differ from that of patients with permanent treatment failure. The criterion of confirmed 1 EDSS point increase at 6 months showed the best sensitivity (76.5%), with satisfactory specificity (89%). Our study shows that a large proportion of patients treated with interferon experience transient treatment failure that may affect outcome interpretation in clinical trials. Using a more strict criterion, as extending time to confirmation of EDSS deterioration, and longer follow-up may reduce this proportion of patients with transient treatment failure and improve the validity of the results attained in clinical trials.
Adjuvants, Immunologic↗
Predictors of treatment failure among tuberculosis patients under DOTS strategy in Egypt.
Treatment failure is a serious problem facing some national tuberculosis (TB) control programmes. Irregularity of treatment is a factor that can lead to treatment failure. A case-control study was carried out in TB centres in Egypt during April 2001-December 2002 aimed at investigating the predictors of treatment failure. We interviewed 119 people with treatment failure and an equal number of cured cases (controls) and their families regarding sociodemographic characteristics, information about TB, information about drugs, treatment compliance, family support and patient-family interaction. Significant risk factors for treatment failure were non-compliance to treatment, deficient health education to the patient, poor patient knowledge regarding the disease and diabetes mellitus as co-morbid condition.
Adult↗
Predictors of treatment failure for ectopic pregnancy treated with single-dose methotrexate.
OBJECTIVE: To determine variables that predict treatment failure after methotrexate (MTX) treatment of ectopic pregnancy. DESIGN: Retrospective cohort study. SETTING: Canadian teaching hospital. PATIENT(S): Sixty patients diagnosed with and treated for ectopic pregnancy. INTERVENTION(S): A single dose of methotrexate (50 mg/m(2)) by i.m. injection. MAIN OUTCOME MEASURE(S): Resolution of serum beta-hCG or clinical evidence of treatment failure. RESULT(S): Treatment failure was observed following methotrexate administration in 65% of cases when initial beta-hCG was >4000 IU/L, but in only 7. 5% of patients when serum beta-hCG was <4000 IU/L (OR = 52.06, 95% CI 4.88-555.56). Patients who presented with pelvic pain without tenderness had treatment failure 56% of the time versus only 17% in those without pain (OR = 9.20, 95% CI 1.02-82.60). Treatment failure also occurred in 53% of patients presenting with vaginal bleeding versus 16% without bleeding (OR = 6.18, 95% CI 0.73-51.93). CONCLUSION(S): Methotrexate should not be used to treat ectopic pregnancy when initial beta-hCG is >4000 IU/L. Caution should also be exercised in using methotrexate for ectopic pregnancy when the patient presents with bleeding or pain even without tenderness.
Abortifacient Agents, Nonsteroidal↗
Treatment failure in acute streptococcal tonsillitis in children over the age of 10 and in adults.
13/169 outpatients (8%) with streptococcal tonsillitis developed a new tonsillitis with the same strain within 2 weeks of completion of therapy (clinical treatment failures) and 24 (14%) remained carriers (bacterial treatment failures) after treatment with phenoxymethylpenicillin (penicillin V) 12.5 mg/kg body weight twice daily for 10 days. The mean serum concentration 60 min after penicillin V administration was 7.84 micrograms/ml. Very large individual differences in serum concentration were found but these differences could not be correlated to treatment failure. About 60% of the patients showed salivary concentrations around 0.03 micrograms/ml. Three strains of streptococci (groups C and G) from patients with bacterial treatment failure had MIC values of 0.06 and 0.12 micrograms/ml. A majority of the patients with clinical treatment failures had contact with individuals with high carrier rates of beta-hemolytic streptococci. It therefore seems likely that some so-called treatment failures in reality are new infections. In clinical treatment failures group A streptococci were twice as common as groups C + G. In bacteriological treatment failures the ratio between A and C + G was 1:1. Patients with nonstreptococcal tonsillitis as well as carriers of groups C and G may appear among bacterial treatment failures.
Acute Disease↗
Prevention of increasing rates of treatment failure by combining sulfadoxine-pyrimethamine with artesunate or amodiaquine for the sequential treatment of malaria.
Combination antimalarial therapy may delay the spread of drug resistance, but clinical data supporting this notion are limited. For 1 year, we studied Ugandan children who were treated for uncomplicated malaria with sulfadoxine-pyrimethamine (SP), SP + amodiaquine (AQ), or SP + artesunate (AS). We compared treatment responses and the prevalence of resistance-conferring mutations of new infections with those of recrudescent infections due to parasites that survived prior treatment. Recrudescent infections were associated with the selection of SP resistance-conferring mutations in all treatment groups, but responses to repeat therapy differed. Compared with initial treatments, treatment of recrudescent infections was associated with a higher rate of treatment failure (hazard ratio [HR], 2.44; P=.01), for the SP group, but with a lower rate of treatment failure (HR, 0.40; P=.08), for the SP + AS group. Treatment failure in the SP + AQ group was uncommon, limiting the analysis of recrudescent parasites. Our results suggest that the use of combination antimalarial therapy in Africa may slow the spread of drug-resistant malaria and prolong the therapeutic life span of available treatment regimens.
Amodiaquine↗
Exercise therapy for depression in middle-aged and older adults: predictors of early dropout and treatment failure.
Psychosocial factors predicting treatment dropout or failure to benefit from treatment were identified in a randomized trial of exercise therapy and pharmacotherapy for major depression. One hundred fifty-six men and women over age 50 diagnosed with major depressive disorder were assigned to a 16-week program of aerobic exercise, medication (sertraline), or a combination of exercise and medication. Thirty-two patients (21%) failed to complete the program and were considered treatment "dropouts." At the end of 16 weeks, 83 patients (53%) were in remission; the remaining patients not in remission were considered treatment "failures." Baseline levels of self-reported anxiety and lift satisfaction were the best predictors of both patient dropout and treatment success or failure across all treatment conditions.
Aged↗
[Miss-management in treatment failure of pulmonary tuberculosis].
PURPOSE: To investigate the risk factor of treatment failure of pulmonary tuberculosis excluding multi-drug resistant cases from the standpoint of both clinical management and tuberculosis control. OBJECT AND METHOD: Retrospective chart review of patients who admitted to Fukujuji Hospital for treatment failure of pulmonary tuberculosis excluding multi-drug resistant cases from Jan. 1993 to Dec. 2003. RESULTS: Out of 24 treatment failure cases available for analysis, 4 cases were associated with chronic tuberculous empyema with broncho-pleural fistula, and among them, chronic empyema was considered to be the main cause of treatment failure in one case. In 6 cases, poor adherence to medication was confirmed or suspected, and 2 of these 6 cases was also associated with miss-management. In 9 cases miss-management was found without poor adherence or chronic empyema, and in 8 out of these 9 cases, miss-management was considered to be the main cause of treatment failure. In 5 cases no apparent risk factor was found, but in 2 out of these 5 cases the ignorance of the results of drug sensitivity tests (and, therefore, miss-management) was strongly suspected. Summing up, in 10 out of 24 cases (41.7%), the miss-management was considered to be the main cause of treatment failure, and it was more frequently seen than poor adherence to medication. CONCLUSION: Clinicians should be aware of these risk factors of treatment failure such as chronic empyema, weak regimen in bacteriological negative cases, rifampicin+ethambutol regimen, and miss-management of drug adverse effect. From the standpoint of tuberculosis control in Japan we considered that, in addition to DOT, strategy to secure the quality of tuberculosis treatment is by all means needed.
Adult↗
Predictors of methotrexate treatment failure in ectopic pregnancy.
OBJECTIVE: To determine the possible predictors of methotrexate treatment failure in ectopic pregnancy. STUDY DESIGN: Fifty-eight patients diagnosed with ectopic pregnancy were treated with methotrexate (50 mg/m2). Selected variables in the history of the patients, the signs and symptoms at the time of admission, transvaginal ultrasound findings and serum beta-human chorionic gonadotropin (beta-hCG) levels on day 1 and 3 were evaluated in a logistic regression model to predict treatmentfailure, defined as tubal rupture. RESULTS: Methotrexate treatment failed in 9 cases (15.5 %). Another 9 cases (15.5%) required a second dose of methotrexate, and no treatment failures were observed in these cases. The presence of subchorionic tubal hematoma in the ectopic gestation (OR = 22.9, CI = 2.7-194.7, p = 0.004), the presence of an embryo (OR = 24, CI = 2.1-269, p = 0.01) and day 1 serum beta-hCG level > or = 3,000 mIU/mL (OR = 27.1, CI = 2.1-342.5, p = 0.01) were the main predictors of treatment failure. Follow-up serum beta-hCG levels > or =3,500 mIU/mL (OR = 42.9, CI = 4.3-421) on day 3 were significant predictors of treatment failure. Follow-up risk score was calculated as > 4 on day 3 by adding day 3 serum beta-hCG level to the admission score. Only 1 treatment failure (2.4%) occurred in 42 patients with an admission score of nil. No treatment failure occurred in 39 patients whose follow-up score was nil. The increase in admission risk (OR = 32.1, CI = 3.8-270, p = 0.001) and follow-up risk (OR = 9.2, CI = 2.4-35.2) were significant predictors of treatment failure. CONCLUSION: Transvaginal ultrasound findings are as important as serum beta-hCG level on the first day of methotrexate treatment. In unruptured cases, day 3 serum beta-hCG level is important to reevaluate the decision to continuefollow-up or perform early surgery for increased risk of treatment failure.
Abortifacient Agents, Nonsteroidal↗