trimethoprim--sulfamethoxazole-drug-combination and Drug-Hypersensitivity

Co-trimoxazole, a sulfonamide antibiotic, is used to treat a variety of infections worldwide, and it remains a common first-line medicine for prophylaxis against Pneumocystis jiroveci pneumonia. However, it can cause severe cutaneous adverse reaction (SCAR), including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms. The pathomechanism of co-trimoxazole-induced SCAR remains unclear.. We aimed to investigate the genetic predisposition of co-trimoxazole-induced SCAR.. We conducted a multicountry case-control association study that included 151 patients with of co-trimoxazole-induced SCAR and 4631 population controls from Taiwan, Thailand, and Malaysia, as well as 138 tolerant controls from Taiwan. Whole-genome sequencing was performed for the patients and population controls from Taiwan; it further validated the results from Thailand and Malaysia.. The whole-genome sequencing study (43 case patients vs 507 controls) discovered that the single-nucleotide polymorphism rs41554616, which is located between the HLA-B and MICA loci, had the strongest association with co-trimoxazole-induced SCAR (P = 8.2 × 10. This study identified HLA-B∗13:01 as an important genetic factor associated with co-trimoxazole-induced SCAR in Asians.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Anti-Infective Agents, Urinary; Asian People; Case-Control Studies; Drug Hypersensitivity; Female; Genetic Predisposition to Disease; HLA-B Antigens; Humans; Malaysia; Male; Middle Aged; Polymorphism, Single Nucleotide; Taiwan; Thailand; Trimethoprim, Sulfamethoxazole Drug Combination; Whole Genome Sequencing; Young Adult

Severe drug hypersensitivity reactions to antibiotics are rare but trimethoprim-sulfamethoxazole (TMP-SMX) is uniquely associated with numerous and varied manifestations including a reaction resembling septic shock, first observed in human immunodeficiency virus (HIV)/AIDS patients. Over the past 25 years about 20 cases have been reported and an association with the virus and related immune system dysregulation was assumed. However, recent reports in adults have recognized similar shock-like reactions in non-HIV infected individuals. Here we review severe TMP-SMX hypersensitivity reactions and within the context of these known reactions, describe three non-HIV infected adolescent patients with shock-like reactions to TMP-SMX observed in one institution over 1.5 years.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Drug Hypersensitivity; HIV Infections; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

To review the literature on trimethoprim-sulfamethoxazole (TMP-SMX)-induced aseptic meningitis (TSIAM) and discuss the features, possible mechanisms, evaluation, and treatment options relevant for the allergist.. A MEDLINE search was performed using the terms aseptic meningitis, trimethoprim-sulfamethoxazole, trimethoprim, and sulfamethoxazole.. Cases were included that fit the case definition of headache, neck pain, or change in mental status with elevated cerebrospinal fluid white blood cell count or protein attributable to TMP-SMX or either medication alone.. Forty-one patient cases were reviewed. There was a predominance of female patients and patients with autoimmune disease reported. Fever, headache, neck pain, and altered mental status were the most common findings reported in TSIAM reactions. Severe reactions ranged from hypotension to seizure and unconsciousness or coma. Typical cerebrospinal fluid findings included elevated white blood cell count with neutrophil predominance, elevated protein, and normal glucose. Symptoms quickly remitted with withdrawal of TMP-SMX, typically over 48 to 72 hours. Full recovery was typically experienced, although permanent paraplegia was reported in 1 case. The mechanism of reaction is unknown, although an IgE-mediated reaction is unlikely. Many patients experienced multiple TSIAM reactions before the diagnosis was made. Diagnosis can be confirmed with drug challenge or graded test dosing when necessary. Patients with TSIAM subsequently reacted to TMP and SMX alone and therefore should be advised to avoid these 2 classes of medication after diagnosis.. TMP-SMX is the most common antibiotic to cause drug-induced aseptic meningitis. By being aware of this reaction, allergists are well poised to diagnose TSIAM and prevent future reoccurrences for the patient.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Child; Drug Hypersensitivity; Female; Humans; Male; Meningitis, Aseptic; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Opportunistic infections continue to cause a significant amount of morbidity and mortality worldwide in patients infected with HIV. Trimethoprim-sulfamethoxazole (cotrimoxazole) is used in the treatment and prophylaxis of several opportunistic infections. In patients with HIV/AIDS, cotrimoxazole use can cause a higher rate of adverse drug reactions than in the general population. Given the cost-effectiveness of cotrimoxazole, the management of these adverse reactions has included continuing the drug (treating-through) and reintroducing the drug at a later date, either using dose-escalation (desensitization), or rechallenge at full dose. This systematic review is the first to examine the differences in patient outcomes between these strategies.. To compare the rate of discontinuation of cotrimoxazole and adverse reactions among the three strategies of treating-through, desensitization, and rechallenge in patients living with HIV who previously had an adverse reaction to cotrimoxazole.. We searched MEDLINE, EMBASE, LILACS, The Cochrane Library, Meeting Abstracts, AIDSTRIALS, ACTIS, Current Controlled Trials, The National Institutes of Health Clinical Trials Registry, and CenterWatch (search date May 2006).. Randomised trials comparing treating-through, rechallenge, or desensitization of cotrimoxazole treatment or prophylaxis in adults (age 18 years or over) and/or children (age 17 years or under).. Two reviewers independently assessed trial eligibility and quality, and extracted data. Where data were incomplete or unclear, a third reviewer resolved conflicts and/or trial authors were contacted for further details.. Three trials that examined cotrimoxazole prophylaxis and involving 268 adults were included. Meta-analysis of these studies found a beneficial effect of using a desensitization protocol over a rechallenge protocol at six months of follow-up for preventing discontinuation of cotrimoxazole (number needed to treat (NNT) 7.14, 95% confidence interval (CI) 4.0-33.0), and for lower incidence of overall hypersensitivity (NNT 4.55, 95% CI 3.03-9.09). No severe hypersensitivity reactions occurred for either protocol in the three studies.. In the small trials included in this review, when compared to cotrimoxazole rechallenge for prophylaxis of opportunistic infections, cotrimoxazole desensitization resulted in fewer treatment discontinuations and overall adverse reactions in HIV-infected patients with a previous history of mild or moderate hypersensitivity to cotrimoxazole. Paediatric data and trials in resource-poor settings are urgently required. Further randomised controlled trials are also needed for the treatment of opportunistic infections, treating-through, adjunctive medications, and different desensitization-dosing schedules.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Desensitization, Immunologic; Drug Hypersensitivity; Humans; Randomized Controlled Trials as Topic; Trimethoprim, Sulfamethoxazole Drug Combination

Drug hypersensitivity has been reported to occur 100 times more commonly in those living with HIV. In the first decade of HIV treatment, this mainly involved drugs used to treat HIV-related infections but now primarily includes drugs used to treat HIV. This review focuses on the current knowledge of the epidemiology, pathophysiology and clinical features of drug hypersensitivity reactions of drugs used in the management of the HIV-infected patient.. Our understanding of the immunogenetics and host predisposition to drug hypersensitivity has been advanced considerably by the antiretroviral drugs abacavir and nevirapine. The association of abacavir hypersensitivity reaction with HLA-B*5701 has been particularly important and provides a basis for genetic screening in the clinic setting.. The increased predisposition of drug hypersensitivity disease in HIV will continue to provide a fertile ground for study of the diverse and complex processes that drive its pathophysiology. Our knowledge of drug hypersensitivity will also increase as the expanding armentarium of antiretroviral therapy is applied to more diverse populations in the developing world. The potential for widespread implementation of HLA-B*5701 screening for abacavir hypersensitivity will set an important precedent for bringing individualized medicine to the clinic and the use of genetic testing to improve drug safety.

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; Dideoxynucleosides; Drug Hypersensitivity; Genetic Predisposition to Disease; HIV Infections; HLA-B Antigens; Humans; Reverse Transcriptase Inhibitors; Trimethoprim, Sulfamethoxazole Drug Combination

Hypersensitivity reactions in patients receiving sulfonamide antibiotics have been frequently documented in the literature, but cross-reactivity with sulfonamide non-antibiotics rarely has been reported.. An 82-year-old woman with a history of hypersensitivity reactions to sulfamethoxazole-trimethoprim resulting in angioedema and rash presented to the emergency department (ED) with angioedema and severe dysphagia, shortness of breath, and rash after receiving valsartan and hydrochlorothiazide (HCTZ) for 4 months. Valsartan was identified as the most likely cause of the symptoms and was discontinued; however, the patient continued to have weekly episodes of angioedema and eventually returned to the ED. HCTZ was discontinued at the second ED visit, and the angioedema disappeared. However, it reappeared after reinitiation of HCTZ, and the patient returned to the ED again; this time with more severe symptoms. After the third ED visit and second hospitalization, HCTZ was permanently discontinued, and the angioedema has not returned. HCTZ was the definite cause of angioedema in this patient based on a score of 9 on the 10-point Naranjo adverse drug reaction probability scale.. Although the probability of true cross-reactivity is not known, clinicians should be aware that an allergic-like reaction to sulfonamide-containing non-antibiotics may occur in patients with known allergies to sulfonamide-containing antibiotics. These patients should be monitored closely when receiving these drugs. Further evaluation is needed to determine whether angioedema should be added to the list of adverse events associated with HCTZ.

Topics: Aged, 80 and over; Angioedema; Anti-Infective Agents; Antihypertensive Agents; Cross Reactions; Drug Hypersensitivity; Female; Humans; Hydrochlorothiazide; Molecular Structure; Probability; Sulfonamides; Trimethoprim, Sulfamethoxazole Drug Combination

Drug hypersensitivity is a major problem in HIV medicine. These reactions limit the choice of antiretrovirals that can be used in a patient and, at times, can lead to failure to administer an adequate regimen. Hypersensitivity reactions occur in a minority of patients, but represent a high cost both to the patient and to health services. Our current understanding of these reactions is based on the hapten and the danger hypotheses, which state that a drug signal by itself is insufficient to induce an immune response but must be accompanied by co-stimulatory or danger signals. Furthermore, individual susceptibility to a hypersensitivity reaction may be determined by genetic factors. In this review, we explore our understanding of the immunological mechanisms of hypersensitivity to drugs used in HIV-positive patients, by using sulphamethoxazole and abacavir as paradigms. A deeper understanding of the mechanism(s) of these reactions will help us in their prevention, diagnosis and treatment.

Topics: Anti-Bacterial Agents; Dideoxynucleosides; Drug Hypersensitivity; Female; HIV Infections; HIV-1; Humans; Male; Reverse Transcriptase Inhibitors; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adrenal Cortex Hormones; Antibodies, Monoclonal; Asthma; Drug Hypersensitivity; Food Additives; Food Hypersensitivity; Humans; Humidity; Hypersensitivity; Immunoglobulin E; Latex Hypersensitivity; Rhinitis; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim/Sulfamethoxazole is the most effective medication used in both the treatment and prevention of Pneumocystis carinii pneumonia (PCP) in patients with HIV/AIDS. Its use, however, is accompanied by a high incidence of adverse reactions, especially fever, myalgia and rash (sulfa hypersensitivity). In a group of our patients, we have examined the clinical parameters at the time of onset of sulfa hypersensitivity, and the success of a desensitization protocol for this adverse event. We also have performed a comprehensive review of the literature on sulfa hypersensitivity and have compared our results to those previously reported in the literature. Our findings indicate that the sulfa hypersensitivity reaction is more likely to develop in patients with advanced disease and that desensitization can restore tolerability to the drug in approximately two thirds of those who attempt it.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Desensitization, Immunologic; Drug Hypersensitivity; Humans; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Drug reactions in patients with HIV infection, e.g. fever or rash, are a frequently occurring clinical problem. These side effects particularly are observed with sulfonamides; however, many other drugs have also shown to induce allergic reactions when given to patients with HIV infection. The production of hydroxylamines has been put forward as one of the explanations for these high incidence of reactions on drugs. Since sulfonamides are the first choice of therapy for the treatment and prophylaxis of Pneumocystis carinii pneumonia, several strategies have been developed to circumvent drug reactions. In general rechallenge or desensitization are recommended in literature. This article discusses the results and risks of rechallenge and desensitization with sulfonamides or other drugs, as mentioned in the literature. Furthermore preliminary results of rechallenge with a sulfonamide, which is not metabolized into hydroxylamines, are presented. From the data in the literature it is concluded that desensitization should be preferred to rechallenge.

Topics: Anti-Infective Agents; Desensitization, Immunologic; Drug Hypersensitivity; Female; HIV Infections; Humans; Hydroxylamines; Male; Pneumonia; Sulfanilamides; Sulfonamides; Trimethoprim, Sulfamethoxazole Drug Combination

The incremental administration of trimethoprim-sulfamethoxazole (i.e., desensitization) in previously hypersensitive HIV-infected patients has been evaluated to date in 7 studies involving more than 10 patients. These studies differ greatly from one to another according to the inclusion criteria, exclusion criteria, and desensitization procedure (duration, lagtime between 2 doses). The efficacy varies from 33% to 100% but one can expect success in 3 out of 4 patients whatever the duration of the desensitization procedure. Short procedures seem better than long ones from the compliance point of view. These different procedures have not been compared each other. The reputation of good tolerance of this procedure is challenged by the recent description of severe life-threatening systemic reaction. Subsequent contra-indications must be ruled out and this procedure must be supervised in hospital.

Topics: Anti-Infective Agents; Desensitization, Immunologic; Drug Hypersensitivity; HIV Infections; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

The increased resistance, intolerance, or allergy to trimethoprim/sulfamethoxazole (TMP/SMX) has brought much attention to alternative treatment of pneumonia caused by Pneumocystis carinii (PCP). Pentamidine is considered when there is documented allergy or intolerance to TMP/SMX. Similarly, either dapsone/trimethoprim or clindamycin/primaquine is effective in the treatment of mild to moderate PCP, but both regimens are contraindicated in glucose 6-phosphate dehydrogenase (G6PD) deficiency. For this purpose, atovaquone should be used in patients who are deficient in G6PD or who are unable to be on TMP/SMX or pentamidine. On the other hand, in severe disease, adjunctive corticosteroids can enhance the efficacy of either TMP/SMX or pentamidine. If these therapies yield no response, trimetrexate with leucovorin has been approved as initial and salvage therapy in severe PCP. We review alternative treatment to TMP/SMX and propose ideal and practical therapeutic and prophylactic guidelines in the treatment and prevention of PCP.

Topics: Adrenal Cortex Hormones; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Atovaquone; Clindamycin; Dapsone; Drug Combinations; Drug Hypersensitivity; Drug Resistance, Microbial; Humans; Leucovorin; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Primaquine; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Trimetrexate

A 22-year-old woman was given trimethoprim plus sulphamethoxazole for a urinary infection (160 and 800 mg, respectively, daily), drugs she had not previously taken. After 2 weeks she noticed a rash of small spots on her trunk. In addition she had nausea and vomiting. The rash faded within 2 days of stopping the drug, but progressive jaundice developed.. SGPT and SGOT concentrations rose to maximally 328 and 83 U/l, total bilirubin to maximally 5.9 mg/dl. There was no evidence for viral hepatitis (B or C, cytomegalovirus, Epstein-Barr), autoimmune hepatitis or primary biliary hepatitis. Liver biopsy showed central acinar cholestasis, which suggested drug-induced liver damage.. The patient's symptoms regressed over several weeks without any specific treatment and 8 weeks after onset of the rash the laboratory tests also became normal. The allergic cause of the cholestatic hepatitis was confirmed by a lymphocyte transformation test.. Clinical suspicion of drug allergy as cause of a cholestatic hepatitis can be confirmed reliably and without any risk to the patient with the lymphocyte transformation test.

Topics: Adult; Anti-Infective Agents, Urinary; Chemical and Drug Induced Liver Injury; Cholestasis, Intrahepatic; Diagnosis, Differential; Drug Hypersensitivity; Female; Humans; Lymphocyte Activation; Remission, Spontaneous; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Hypersensitivity to zidovudine is an uncommon complication of antiretroviral therapy. Manifestations range from isolated fever to anaphylaxis. Fever and rash are the most common features. Diagnosis is made by rechallenge, although some patients have antibodies to zidovudine. Treatment is supportive, and symptoms resolve on withdrawal of the medication.

Topics: Adult; Anaphylaxis; Drug Hypersensitivity; Humans; Male; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

The treatment and the prevention of Pneumocystis carinii pneumonia (PCP) is based on trimethoprim-sulfamethoxazole. However, hypersensitivity reactions occur often in HIV-infected patients. In this study, clinical and biological parameters of 27 PCP-patients treated by this drug association were analyzed. We divided the drug reactions into two groups according to the severity. A drug reaction occurred in 59.2% of the patients and was note as a mild reaction in 18.5% of the cases and as a severe reaction in 40.7%. An initial high eosinophil count was noted in patients who may present future drug reaction. This difference was more significant in patients who may present severe drug reaction. No other clinical or biological factors were predictive of hypersensitivity. The immune status of HIV-disease, drug therapy, and drug mechanisms were discussed.

Topics: Adult; AIDS-Related Opportunistic Infections; Drug Hypersensitivity; Female; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Predictive Value of Tests; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Cutaneous reactions to penicillin-type antibiotics are usually caused by IgE-mediated reactions directed toward the beta-lactam ring (in penicillin, ampicillin-amoxicillin, and cephalosporins). These allergic reactions may be reliably diagnosed (96% to 99% of the time) with a battery of skin tests derived from penicillin. A few individuals have been identified in Spain, and now Canada, who react to side chains of the beta-lactam antibiotics (and not the beta-lactam ring). Nonallergic cutaneous or systemic reactions to trimethoprim sulfamethoxazole (TMP-SMX) are now an emerging problem among HIV-infected patients. Life-threatening reactions have been described in HIV-infected infants who were rechallenged with TMP-SMX. New 10-day and 48-hour desensitization procedures have been used successfully in some TMP-SMX-reactive patients. Stevens-Johnson syndrome and Lyell's syndrome (toxic epidermal necrolysis) are the most serious of the antibiotic-associated cutaneous reactions. These reactions may be caused by an immune reaction similar to graft-versus-host syndrome. Corticosteroids have been shown to be helpful in the management of Stevens-Johnson syndrome. Although the mortality of toxic epidermal necrolysis is usually high, several children with this disorder have been successfully treated in a burn unit.

Topics: Anti-Bacterial Agents; Child; Drug Hypersensitivity; Humans; Lactams; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole is an important medication for the treatment and prevention of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. Use of this medication has been limited by the high frequency of adverse reactions that occur in patients with human immunodeficiency virus disease. This article reviews the incidence and spectrum of adverse reactions and options for continuing therapy with trimethoprim-sulfamethoxazole in human immunodeficiency virus-infected patients who have adverse reactions.

Topics: AIDS-Related Opportunistic Infections; Drug Hypersensitivity; HIV Infections; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Nocardia farcinica, the etiologic agent of bovine farcy, is microbiologically related to but distinct from Nocardia asteroides. N. farcinica is noted for its propensity to cause serious systemic infection in both normal and immunocompromised hosts and its marked degree of resistance to multiple antimicrobial agents. We present a case in which a nonimmunocompromised patient who sustained a contaminated facial laceration developed an abscess due to N. farcinica with underlying osteomyelitis. The severity of the infection necessitated surgical debridement followed by administration of intravenous amikacin therapy. The isolate was susceptible to amikacin and trimethoprim-sulfamethoxazole but resistant to erythromycin in vitro. Therapy with trimethoprim-sulfamethoxazole was started but was discontinued because of the patient's intolerance to the drug. Intramuscular amikacin was substituted, resulting in complete resolution of the infection. The history, epidemiology, and microbiological characteristics of this interesting and unusual microorganism are reviewed.

Topics: Abscess; Amikacin; Debridement; Drug Hypersensitivity; Drug Resistance, Microbial; Facial Injuries; Humans; Male; Middle Aged; Nocardia; Nocardia Infections; Skin Diseases, Bacterial; Trimethoprim, Sulfamethoxazole Drug Combination; Wound Infection

Computed tomography (CT) of the chest provides important information toward the diagnosis of drug-induced lung disease. CT's ability to demonstrate subtle parenchymal and pleural changes, small nodules, and adenopathy is valuable in the early detection of drug-related reactions. CT is also of value in monitoring the appearance, progression, and resolution of pulmonary damage in patients receiving potentially toxic drugs. The CT appearances of specific drug reactions are reviewed, including the spectrum of CT findings in bleomycin toxicity and amiodarone-induced lung disease.

Topics: Amiodarone; Bleomycin; Drug Hypersensitivity; Humans; Immunoblastic Lymphadenopathy; Lung; Lung Diseases; Radiography, Thoracic; Tomography, X-Ray Computed; 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

To evaluate cross reactivity between sulfonamide antimicrobials and celecoxib in patients with histories of allergies to sulfonamide antimicrobials.. Immunocompetent patients with a history of sulfonamide antimicrobial allergy who were being considered for therapy with celecoxib were prospectively enrolled. Sulfamethoxazole and trimethoprim skin prick and intradermal testing and/or an in vitro lymphocyte toxicity assay were performed. If skin testing was negative, an oral challenge with sulfamethoxazole and trimethoprim was performed. Oral challenges with celecoxib were administered to all patients.. Twenty-eight immunocompetent patients (26 female; mean age 60 years) were evaluated. History of sulfonamide antimicrobial allergy included urticaria (n = 7), cutaneous eruptions (n = 9), and other (n = 12). Four of the 28 patients who were skin prick tested were positive to sulfamethoxazole and two of the ten patients who underwent in vitro testing were positive to sulfamethoxazole. All 28 patients were administered celecoxib and tolerated the medication. Phone call follow up in 25 patients disclosed that 15 patients continued to take celecoxib, while five patients did not take celecoxib following the oral challenge, and five discontinued celecoxib due to adverse effects, lack of drug efficacy or physician preference.. Confusion exists regarding the potential for cross reactivity between sulfonamide antimicrobials and other sulfonamide-containing compounds. The six sulfonamide-allergic patients tolerated celecoxib uneventfully. This pilot study supports the hypothesis that the potential for cross-reactivity between celecoxib and sulfonamide antimicrobials appears to be low. However, further investigations are required to confirm this.

Topics: Administration, Oral; Adult; Aged; Anti-Infective Agents; Celecoxib; Cross Reactions; Cyclooxygenase Inhibitors; Drug Eruptions; Drug Hypersensitivity; Female; Humans; Male; Middle Aged; Pilot Projects; Pyrazoles; Skin Tests; Sulfonamides; Trimethoprim, Sulfamethoxazole Drug Combination

Sulfonamides are drugs extensively used in the management of AIDS patients. However, the use of sulfonamides is often associated with the development of allergic reactions, provoking the substitution of the drug (by another that may be less effective); alternatively attempts are made to desensitize the patient.. Compare two drug regimens (full vs. escalating doses) for the oral desensitization of AIDS patients allergic to sulfonamides.. AIDS patients with previous allergic reactions to sulfonamides and requiring prophylaxis against Pneumocistis carinii, central nervous system toxoplasmosis and diarrhea caused by Isospora belli were randomly assigned to a group receiving a routine dose of cothrimoxazole, or another that received escalating doses of an oral suspension of the same drug, initiating with 75 mg/day of sulfamethoxazole that was doubled every 48 hours till the full dose was reached, if no allergic reaction occurred. Patients were monitored for at least 6 months after enrollment in the trial. The major end-point was the ability to maintain prophylactic treatment after that period of time. Plasma viral load (PVL) and CD(4)/CD(8) counts were measured at baseline. Liver enzymes and hematological parameters were measured at baseline and after 1, 3 and 6 months.. Eighteen patients were enrolled in the study (15 men and 3 women), with ages ranging from 30 to 57 years (mean 39.9). The mean CD(4) counts were slightly higher for patients receiving a full dose; there was also a trend towards higher baseline CD(8) counts among patients developing new reactions. The mean PVL was similar among the patients in both desensitization groups. The incidence of new allergic reactions was identical (40%) in the two groups. All adverse reactions were mild and no significant increase in liver enzymes were observed.. Dose regimen is not a predictor of the development of new allergic reactions amongst patients challenged with sulfonamides after an initial allergic reaction.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; CD4-CD8 Ratio; Desensitization, Immunologic; Drug Administration Schedule; Drug Hypersensitivity; Female; Humans; Male; Middle Aged; Pilot Projects; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Viral Load

Our study was undertaken to evaluate if desensitization treatment is more effective than rechallenge in preventing hypersensitivity reactions in HIV-positive patients with previous allergic reactions to TMP-SMX; the secondary aim was to evaluate the frequency of reactions to TMP alone. This was a randomized, multicentre open study. Patients with previous documented hypersensitivity to TMP-SMX who required primary or secondary PCP prophylaxis were enrolled; subjects who had previously had serious adverse reactions to TMP-SMX were excluded. All eligible patients assumed 200 mg TMP for 14 days and in case of no reactions were randomized for desensitization or rechallenge with TMP-SMX. The patients were then followed up by periodical visits for six months. Seventy-three patients were enrolled; 14 subjects (19%) presented reactions on TMP alone during the pre-enrollment phase. The remaining 59 subjects were randomly assigned to the two treatment groups: 34 carried out desensitization (group 1) and 25 rechallenge (group 2) with TMP-SMX. Seven patients in group 1 (20.5%) and seven in group 2 (28%) showed hypersensitivity reactions during treatment; this difference was not statistically significant. No serious reaction occurred in either group. This study showed the comparable effectiveness of the desensitization procedure and rechallenge in patients with a previous, not serious, allergic reaction to TMP-SMX.

Topics: Adult; Desensitization, Immunologic; Drug Hypersensitivity; Female; HIV Seropositivity; Humans; Male; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

This trial was conducted to study the frequency of the slow acetylator phenotype in asymptomatic HIV patients having no previous reaction to sulfa-drugs, and to compare this frequency with the frequency found in healthy controls. Results show that HIV alone is not capable of modifying the acetylator phenotype; the prevalence of slow acetylator phenotype is the same in immune competent subjects and HIV-positive patients. It is more common in HIV-positive patients with a CD4+ lymphocyte count of less than 200 mm-3.

Topics: Acetylation; Adult; Anti-Infective Agents; Drug Hypersensitivity; Female; HIV Infections; HIV Seropositivity; Humans; Kinetics; Male; Phenotype; Trimethoprim, Sulfamethoxazole Drug Combination

The pathogenesis of hypersensitivity to trimethoprim-sulfamethoxazole (TMP-SMX) is supposed to be associated with the slow acetylation phenotype. This pharmacogenetic defect is associated with the mutations of the arylamine N-acetyltransferase (NAT2) encoding gene. The aim of the study was to compare the usefulness of the acetylation phenotype and NAT2 coding genotype in the prediction of idiosyncratic reaction to Cotrimoxazole in infants. The study was carried out in the group of 20 infants, aged 2-12 months (mean age 6.3 months) treated with Cotrimoxazole, administered at 100 mg/kg b.w./24 h doses. In seven children (35%) no adverse effects of the treatment have been observed, whereas in 13 (65%) children various adverse effects occurred as a result of the therapy, such as rash (4 children), granulocytopenia with anemization (5 children) or liver impairment (4 children). The acetylation phenotype of each child was determined on the basis of urine of N-acetyl isoniazid/isoniazid ratio, after ingestion of isoniazid as a model drug. Furthermore we used polymerase chain reaction (PCR) followed by the analysis of restriction fragments length polymorphism (RFLP) technique to identify the known mutant alleles of the NAT2 gene. It has been presumed that the genotype determining fast acetylation contains at least one of wild-type allele. No correlation has been found between the observed adverse effects of Cotrimoxazole and age, gender and acetylation phenotype. However, it has been demonstrated that the risk of adverse effects of Cotrimoxazole is considerably higher in children with mutations of the NAT2 encoding gene. The comparison of the results from PCR-RFLP genotyping with phenotyping suggested that in infants, the NAT2 genotype rather than phenotype provides the basis for the detection of hypersensitivity to TMP-SMX.

Topics: Acetylation; Alleles; Anti-Infective Agents; Arylamine N-Acetyltransferase; Drug Hypersensitivity; Female; Genotype; Humans; Infant; Male; Pneumonia, Pneumocystis; Poland; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Trimethoprim, Sulfamethoxazole Drug Combination

Hydroxylamine derivatives of sulfamethoxazole may be the reactive metabolites that cause adverse reactions to trimethoprim-sulfamethoxazole (TMP-SMX). The increased frequency of reactions observed in HIV-positive individuals is hypothesized to be due to systemic glutathione deficiency and a decreased ability to scavenge these metabolites. Two hundred and thirty-eight patients were randomized to receive or not receive N-acetylcysteine (3 g of the 20% liquid solution) 1 hour before each dose of TMP-SMX (trimethoprim 80 mg, sulfamethoxazole 400 mg) twice daily, which was initiated as primary Pneumocystis carinii pneumonia prophylaxis. Forty-five patients had to discontinue TMP-SMX within 2 months because of fever, rash, or pruritus including 25 of 102 patients (25%) who were receiving TMP-SMX alone and 20 of 96 patients (21%) who were randomized to TMP-SMX and N-acetylcysteine. The difference between treatment groups is 4% (95% confidence interval [CI]: -16%, +9%). No independent association was found with the hypersensitivity reaction and age, gender, race, HIV risk factor, prior AIDS, concurrent use of fluconazole, or baseline CD4. N-acetylcysteine at a dose of 3 g twice daily could not be shown to prevent TMP-SMX hypersensitivity reactions in patients with HIV infection.

Topics: Acetylcysteine; Adult; Anti-Infective Agents; Drug Hypersensitivity; Female; Free Radical Scavengers; HIV Infections; Humans; Incidence; Male; Middle Aged; Outcome Assessment, Health Care; Pneumonia, Pneumocystis; Primary Prevention; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Hypersensitivity reactions to trimethoprim/sulfamethoxazole occur with a high frequency in human immunodeficiency virus (HIV)-infected patients. This study tested whether differences in oxidative metabolism and plasma reductive capacity correlate with sulfonamide intolerance in patients with HIV. Eighteen stable outpatients with HIV were prospectively studied. Nine patients had documented histories of hypersensitivity reactions to trimethoprim/sulfamethoxazole and nine did not. Urinary caffeine metabolite ratios assessed the activity of two oxidative enzymatic pathways: cytochrome P-450 1A2 (demethylation) and 8-hydroxylation. Plasma cyst(e)ine was used as a measure of reductive capacity. The trimethoprim/sulfamethoxazole-intolerant group showed greater rates of 8-hydroxylation, lower rates of demethylation, and lower cyst(e)ine levels. The results of this pilot study extend previous observations of differences in oxidative metabolism and reductive capacity that exist within the population of HIV-infected individuals. In addition, these findings lay the groundwork for future interventional studies that could use agents to inhibit sulfonamide oxidation and increase reductive capacity in sulfonamide-intolerant patients with HIV when rechallenged with trimethoprim/sulfamethoxazole.

Topics: Adult; Anti-Infective Agents; Caffeine; Cysteine; Drug Hypersensitivity; Female; HIV Infections; Humans; Male; Oxidation-Reduction; Phosphodiesterase Inhibitors; Pilot Projects; Prospective Studies; Sulfonamides; Trimethoprim, Sulfamethoxazole Drug Combination

To establish whether an outpatient, 2-day oral desensitization protocol would be both safe and effective in HIV-infected patients with previous trimethoprim-sulfamethoxazole (TMP-SMX) intolerance.. A single center trial of TMP-SMX desensitization in HIV-infected patients with prior TMP-SMX hypersensitivity reactions.. HIV-infected patients with CD4 lymphocyte counts < 250 x 10(6)/l cells or CD4% < 20% with previous non-life-threatening hypersensitivity reactions to TMP-SMX were eligible. The desensitization protocol utilized 40 graduated doses over 36 h; the first 28 doses (7.5 h) of the protocol were given in an outpatient clinic with the remaining doses taken at home.. Twenty-seven (60%) of the 45 subjects completed the protocol and were subsequently maintained on daily TMP-SMX without adverse reactions (mean follow-up, 9 months; range, 4-16 months). Patients with CD4 counts < 100 x 10(6)/l cells were just as likely as patients with higher CD4 counts to tolerate the desensitization. No patient required hospitalization for treatment of an adverse reaction.. Oral desensitization to TMP-SMX in HIV-infected patients is a useful option in the management of patients with advanced HIV disease and prior intolerance to TMP-SMX.

Topics: Administration, Oral; AIDS-Related Opportunistic Infections; CD4-Positive T-Lymphocytes; Drug Hypersensitivity; Drug Tolerance; Humans; Pneumonia, Pneumocystis; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

A multicenter placebo-controlled trial of early short-term high-dose methylprednisolone enrolled 78 patients with moderate to severe Pneumocystis carinii pneumonia (PCP) complicating HIV infection. The mean pressure of oxygen (PO2) at study entry was 55 mm Hg for the 71 patients who had blood gases monitored while breathing room air. Patients were randomized to receive methylprednisolone (40 mg) or placebo parenterally twice daily for 10 days, and the first dose of study medication was given within 24 h of the first dose of antimicrobial therapy for PCP. The primary end point included death, need for mechanical ventilation for > 6 days, or a partial PO2 < 70 mm Hg while breathing room air 10 days after initiation of treatment. There was no statistically significant difference in the primary end point between patients randomized to corticosteroid (CS) or placebo (PL) (p = 0.522; 95% CI = -0.30, 0.16). The incidence of superinfections during therapy or of other HIV-associated infections or malignancies in the 6 months following treatment for PCP was not significantly different between the two groups. More patients randomized to placebo had to discontinue treatment with trimethoprim-sulfamethoxazole because of hypersensitivity than those randomized to corticosteroids (p = 0.039). We conclude that addition of corticosteroids does not significantly affect the outcome of PCP in patients with HIV and a PO2 < 70 mm Hg on room air at presentation but lowers the incidence of hypersensitivity reactions to trimethoprim-sulfamethoxazole.

Topics: Adult; AIDS-Related Opportunistic Infections; Chemotherapy, Adjuvant; Double-Blind Method; Drug Hypersensitivity; Female; HIV Infections; Humans; Male; Methylprednisolone; Pneumonia, Pneumocystis; Respiratory Function Tests; Survival Analysis; Trimethoprim, Sulfamethoxazole Drug Combination

In a controlled randomized study among 48 patients undergoing 75 courses of aggressive antileukemic therapy, it was shown that cotrimoxazole was less effective than penicillin G in preventing septicemia due to viridans streptococci. Both antibiotics were given intravenously. During 35 episodes of chemotherapy in the group of patients on penicillin G only, one patient developed a streptococcal bacteremia; this contrasted with bacteremia and septicemia in seven patients during 40 episodes in the group on cotrimoxazole. In three of these seven patients, septicemia was associated with respiratory failure and it was the cause of death in one. Both aerobic gram-negative rods and streptococci which caused infection despite cotrimoxazole prophylaxis were resistant to cotrimoxazole. Side effects such as hypersensitivity and favorable or unfavorable interaction with the oral selective decontamination regimen were similar for the two drugs, with the exception of colonization with Candida spp, which occurred more often in patients on cotrimoxazole than in patients on penicillin.

Topics: Agranulocytosis; Antineoplastic Agents; Bacteremia; Drug Hypersensitivity; Drug Interactions; Drug Resistance, Microbial; Humans; Length of Stay; Leukemia; Penicillin G; Streptococcal Infections; Streptococcus; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Hemophiliacs infected with human immunodeficiency virus with a history of hypersensitivity reaction to a combination product of trimethoprim and sulfamethoxazole were desensitized orally. Six of the seven patients included in the study successfully completed the desensitization protocol and received trimethoprim-sulfamethoxazole for 5 to 7 months after desensitization (mean length of treatment, 5.7 months) for prophylaxis of Pneumocystis carinii pneumonia. The small number of patients and the short follow-up allow us to suggest that oral desensitization may be an effective and inexpensive means to treat hemophiliacs infected with human immunodeficiency virus with trimethoprim-sulfamethoxazole as prophylaxis against Pneumocystis carinii pneumonia.

Topics: Administration, Oral; Adolescent; Adult; AIDS-Related Opportunistic Infections; CD4-CD8 Ratio; CD4-Positive T-Lymphocytes; Child; Desensitization, Immunologic; Drug Hypersensitivity; Female; Follow-Up Studies; Hemophilia A; HIV Infections; Humans; Leukocyte Count; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Based on the radioallergosorbent test (RAST), the authors have developed a series of assays to detect IgE and IgG antibodies against a number of frequently used drugs. In this system drugs bound covalently to cellulose paper are incubated with serum and washed; the hapten-specific IgE and IgG antibodies are then qualified and quantified by means of 125I-labelled anti-human IgE and IgG respectively. Thus far the sera of 1,228 patients have been analyzed following therapy with betalactam antibiotics, co-trimoxazole, salicylates, pyrazolones, flavonoids and tetrahydroisoquinoline. The induction of IgG antibodies is a frequent occurrence and that of IgE rare. Isolated high titers of IgE are associated mainly with anaphylactic reactions; in the presence of simultaneously raised IgG titers such side reactions are often absent. Highest IgG titers were found in patients with immune hemolysis after betalactam antibiotics, flavonoids and tetrahydroisoquinoline. In the other types of side reaction specific IgG titers were not significantly higher than in patients without side reactions. The estimation of circulating antibodies against drugs cannot yet be utilized diagnostically except in the rare cases of anaphylactic side reactions. However, the method described permits specific and sensitive detection of sensitization and is suited for scientific purposes.

Topics: Clinical Trials as Topic; Drug Combinations; Drug Evaluation; Drug Hypersensitivity; Flavonoids; Humans; Immunoglobulin E; Immunoglobulin G; Penicillins; Pyrazoles; Pyrazolones; Radioimmunosorbent Test; Salicylates; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

The evaluation of adverse drug reactions (ADR) in clinical practice is difficult and imprecise. Establishing a causal relationship may not be possible, and data on incidence cannot be obtained because the number of patients treated is not known. This article describes the ADR reported during the clinical trial program of cinoxacin, a synthetic antibacterial drug used to treat urinary tract infections. Results from 2,801 patients who received cinoxacin showed that 5 per cent reported ADR that were probably or definitely drug induced, and 10 per cent reported ADR in which the relationship was uncertain. There was no relationship between number of reports and patient's age, drug dose, or duration of treatment. Adverse drug reactions affecting the gastrointestinal system were reported by 5.5 per cent of the patients, those involving the central nervous system by 4.3 per cent, and hypersensitivity reported by 2.4 per cent. In the comparative studies, patients treated with cinoxacin reported fewer ADR than those treated with nalidixic acid, furadantin, amoxicillin, or trimethoprim-sulfamethoxazole. Although problems in the assessment and evaluation of ADR still exist, it is hoped that the results from the formal trial program will be representative of those seen in clinical practice.

Topics: Adult; Aged; Amoxicillin; Anti-Infective Agents, Urinary; Central Nervous System Diseases; Cinoxacin; Clinical Trials as Topic; Drug Combinations; Drug Hypersensitivity; Gastrointestinal Diseases; Humans; Middle Aged; Nalidixic Acid; Nitrofurantoin; Pyridazines; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

A randomised single-blind clinical trial compared cinoxacin (500 mg every 12 hours) to co-trimoxazole (160 mg trimethoprim, 800 mg sulphamethoxazole every 12 hours) in the treatment of 63 patients with urinary tract infections. The symptomatic response was 73% for both drugs. Bacterial eradication was achieved in 81% and 100% of patients receiving cinoxacin and co-trimoxazole respectively. Three patients receiving co-trimoxazole stopped treatment because of adverse reactions. We conclude that cinoxacin is an effective and safe antibacterial agent in the treatment of urinary tract infections.

Topics: Adolescent; Adult; Aged; Anti-Infective Agents, Urinary; Bacteriuria; Cinoxacin; Clinical Trials as Topic; Cystitis; Drug Combinations; Drug Hypersensitivity; Escherichia coli Infections; Female; Humans; Male; Middle Aged; Nausea; Pyelonephritis; Pyridazines; Random Allocation; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

This cohort study describes the adaptation of a widely used penicillin allergy clinical decision tool for evaluation of trimethoprim-sulfamethoxazole allergy.

Topics: Anti-Bacterial Agents; Clinical Decision Rules; Drug Hypersensitivity; Humans; Hypersensitivity; Sulfonamides; Trimethoprim, Sulfamethoxazole Drug Combination

Antibiotic allergy is a big problem that may affect the treatment and life quality of patients with cystic fibrosis (CF).. To evaluate predictive factors for confirmed antibiotic hypersensitivity in children with CF.. In this case-controlled study, we examined 15 patients with CF who had been confirmed with antibiotic allergy. Additionally, we included a control group of age- and gender-matched 45 CF patients with no antibiotic allergy. The diagnosis of antibiotic allergy was confirmed in the presence of a compatible history and a positive response in the drug skin test or provocation test. Multiple drug hypersensitivity was classified according to the temporal relationship of antibiotics: (i) distant, (ii) simultaneous, and (iii) sequential. The data were analyzed by conditional logistic regression.. β-lactam allergy was confirmed in eight patients (ceftazidime n = 5, piperacillin-tazobactam n = 3) and non-β-lactam allergy was confirmed in two patients (ciprofloxacin n = 1, azithromycin n = 1). Additionally, multiple drug hypersensitivity in five patients (distant n = 4, sequential n = 1), among whom two patients showed hypersensitivity against ceftazidime/piperacillin-tazobactam+ ciprofloxacin/levofloxacin, two patients showed hypersensitivity against ceftazidime+ ciprofloxacin n = 2, and one patient showed hypersensitivity against piperacillin-tazobactam+ amikacin+ trimethoprim-sulfamethoxazole. All patients (n = 13) with confirmed β-lactam allergy were meropenem tolerant. Multivariate analysis indicated that immediate reactions (, p < 0.001) and allergic evaluation in the first six months after the reaction (p = 0.036) were significant risk factors for the prediction of antibiotic hypersensitivity.. Beta-lactam antibiotic allergy is the most commonly confirmed drug allergy in children with CF. However, unlike normal children, ceftazidime and piperacillin-tazobactam account for the majority.

Topics: Amikacin; Anti-Bacterial Agents; Azithromycin; Case-Control Studies; Ceftazidime; Child; Ciprofloxacin; Cystic Fibrosis; Drug Hypersensitivity; Humans; Levofloxacin; Meropenem; Piperacillin; Retrospective Studies; Tazobactam; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Bacterial Agents; Drug Hypersensitivity; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Anti-Bacterial Agents; Drug Combinations; Drug Hypersensitivity; Female; Humans; Male; Middle Aged; Sulfonamides; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Topics: Adult; Antigen Presentation; Antigen-Presenting Cells; CD4-Positive T-Lymphocytes; Cells, Cultured; Drug Hypersensitivity; Female; Gene Expression; Histocompatibility Antigens Class II; HLA-B13 Antigen; Humans; Leukocytes, Mononuclear; Lymphocyte Activation; Male; T-Cell Antigen Receptor Specificity; T-Lymphocytes; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Desensitization, Immunologic; Drug Hypersensitivity; HIV Infections; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

The fixed drug eruption is a non-immediate hypersensitivity reaction to drug, characterized by recurrent erythematous or violaceous, rounded, well-defined border plaques, which always appear in the same location every time the culprit drug is administered. The usual practice is to avoid the drug involved and to use a structurally different drug. However, there are situations in which there is no safe and effective therapy. In such situations, desensitization is the only option. We describe the case of a patient who presented fixed eruption due to sulfamethoxazole-trimethoprim, who underwent successful desensitization, but required a repeat procedure twice due to relapse after inadvertent full-dose reintroduction. In non-immediate hypersensitivity reaction to drug, the indication is controversial and there is no technical standardization. Furthermore, the time at which such tolerance is lost after discontinuing the drug involved is unknown. In severe non-immediate reactions of types II and III, desensitization is contraindicated. The patient underwent desensitisation to sulfamethoxazole-trimethoprim three times - the first with recurrence of lesions and the second and third without manifestations, all concluded successfully and with no premedication.

Topics: Aged; Desensitization, Immunologic; Drug Eruptions; Drug Hypersensitivity; Humans; Male; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Antibiotics are among the most common prescriptions in children, and non-β-lactam antibiotics (NBLAs) account for almost half of those prescribed in Australian pediatric hospitals. Despite this, data on NBLA hypersensitivity in children are limited. This study describes reported hypersensitivity reactions to NBLAs in children and the results of allergy evaluation.. Children with a suspected NBLA allergy who had skin testing and/or an intravenous or oral challenge test (OCT) between May 2011 and June 2018 were included. Patients were excluded if they were >18 years old or did not complete the allergy evaluation for any reason other than allergic reaction.. Over the 7-year study period, 141 children had 150 allergy evaluations of 15 different NBLAs. The median time from the initial reported reaction to allergy evaluation was 1.9 (range 0.1-14.9) years. Overall, 27 of the 150 (18.0%) challenge tests to NBLAs had positive results, with the rate of positive OCT results being highest for trimethoprim-sulfamethoxazole (15 of 46; 32.6%) and macrolides (8 of 77; 10.4%). Although 4 children reported initial anaphylactic reactions, no patients had severe symptoms on rechallenge or required adrenaline. Of the challenges that had positive results, the majority of children (23 of 27; 85.2%) had symptoms on repeat challenge similar to those that were initially reported.. Overall, 8 of 10 children with NBLA allergy could be delabeled. On average, patients waited 1.9 years to be rechallenged. Timely access to allergy evaluation to delabel these patients is needed to preserve first-line antibiotics.

Topics: Adolescent; Anti-Bacterial Agents; Child; Child, Preschool; Drug Hypersensitivity; Female; Hospitals, Pediatric; Humans; Infant; Macrolides; Male; Retrospective Studies; Skin Tests; Trimethoprim, Sulfamethoxazole Drug Combination; Victoria

Topics: Anti-Bacterial Agents; Drug Combinations; Drug Hypersensitivity; Humans; Sulfonamides; Trimethoprim, Sulfamethoxazole Drug Combination

This study aimed to investigate the risk factors of hydroxychloroquine (HCQ)-induced hypersensitivity in patients with systemic lupus erythematosus (SLE) and to propose a simple dose-escalation regimen in cases of mild HCQ-induced hypersensitivity.. We identified patients with SLE who started HCQ between 2009 and 2018 and cases of HCQ-induced hypersensitivity by reviewing the electronic medical charts. A simple dose-escalation regimen, starting at 40 mg/day with weekly increments of 40 mg/day to 200 mg/day, was used in patients with HCQ-induced hypersensitivity who did not require hospitalization or systemic steroid therapy. We then compared the clinical parameters of patients with and without HCQ-induced hypersensitivity and evaluated the success of our dose-escalation regimen.. We enrolled 302 patients with SLE and identified 25 cases of HCQ-induced eruption (8.3%). The mean Naranjo score of these patients was 5.1 ± 1.4 (min 3, max 8), and all 25 patients received a 'possible' (9) or 'probable' (16) score. A mild, generalized, maculopapular rash occurred in 24 patients, and urticaria occurred in one patient at 24 days (interquartile range 15-40 days) after the start of treatment. The proportion of cyclophosphamide use, glucocorticoid consisting of prednisolone 20 mg/day or more, and initiation of SMX-TMP within 28 days were higher in patients with skin eruptions. On multivariate analysis, only cyclophosphamide use was identified as a risk factor of HCQ-induced hypersensitivity (odds ratio = 12.3 (95% confidential interval 1.4-14.3)). Thirteen of the 14 patients on the dose-escalation regimen (92.9%) tolerated continued HCQ treatment. One patient re-experienced eruptions on day 10 day after starting HCQ.. Mild late reactions are common in HCQ-induced hypersensitivity. A simpler dose-escalation regimen enables safe and easier reintroduction of HCQ but should not be applied to patients with immediate reactions or moderate late reactions.

Topics: Adult; Anti-Bacterial Agents; Antirheumatic Agents; Clinical Protocols; Cyclophosphamide; Dose-Response Relationship, Drug; Drug Hypersensitivity; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Hydroxychloroquine; Immunosuppressive Agents; Japan; Lupus Erythematosus, Systemic; Male; Middle Aged; Prednisolone; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (TMP-SMX) is the first-line agent for Pneumocystis jiroveci pneumonia (PJP) prophylaxis for solid organ transplant (SOT) recipients because of its efficacy for this indication, extended antimicrobial coverage, and favorable cost. Reported sulfonamide allergy is not uncommon and often results in TMP-SMX avoidance. Desensitization offers an efficacious and cost-effective alternative to TMP-SMX avoidance. Herein, we reviewed our experience with desensitization during the index transplant hospitalization among 52 SOT recipients with history of a non-anaphylactic sulfonamide allergy. Of those enrolled in the desensitization protocol, 92% (48/52) completed the protocol, with nearly 80% (41/52) still on TMP-SMX at 3 months without adverse reaction. Eleven patients discontinued TMP-SMX (7 for allergic reactions and 4 for non-allergic reasons) and switched to pentamidine. A cost savings of $575 per desensitization was calculated based on annual wholesale drug prices, for a total savings of $23 575. Additionally, the protocol did not delay discharge in any patient nor was it associated with any severe allergic reactions. These findings suggest TMP-SMX desensitization is safe and effective in SOT recipients with a history of non-anaphylactic, non-life-threatening sulfonamide hypersensitivity.

Topics: Cost Savings; Desensitization, Immunologic; Drug Hypersensitivity; Feasibility Studies; Female; Humans; Male; Middle Aged; Organ Transplantation; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Severity of Illness Index; Transplant Recipients; Trimethoprim, Sulfamethoxazole Drug Combination

The N-acetyltransferase 2 (NAT2) enzyme has been understudied in Nigerians including genotype-phenotype association studies.. The aim of this study was NAT2 haplotype identification and genotype-phenotype investigations in HIV-positive and HIV-negative Nigerians.. Phenotypes included self-reported sulphonamide hypersensitivity survey, experimental and computational NAT2 phenotyping. The NAT2 gene was amplified by PCR. Gene sequencing used ABI 3730 and Haploview 4.2 for haplotype reconstruction. Genotype-phenotype analyses used the χ P-value and odds ratio with a 95% confidence interval.. Self-reported sulphonamide hypersensitivity showed a prevalence of 3.1 and 12.4% in HIV-positive and HIV-negative Nigerians, respectively. NAT2 genetic variants 191G>A, 282C>T, 341T>C, 481C>T, 590G>A, 803A>G and 857G>A were not significantly different between both groups (odds ratio=0.87; 95% confidence interval: 0.54-1.38, P=0.55). Nine haplotypes: NAT2*4, NAT2*12A, NAT2*13A, NAT2*5B, NAT2*6A, NAT2*7B, NAT2*5C, NAT2*14B and NAT2*14A had frequencies more than 1%, whereas NAT2*12B had 1.1% in the HIV-positive and 0.4% in the HIV-negative group. Overall, slow acetylator haplotypes made up 68%. The NAT2*12 signature single-nucleotide polymorphism was in high linkage disequilibrium with signature single-nucleotide polymorphism for NAT2*13 (D'=0.97, r=0.61) and NAT2*5 (D'=0.98, r=0.64). Genotype-phenotype association analysis showed haplotypes NAT2*13A, NAT2*5C, NAT2*7B and NAT2*14A to be associated strongly with the slow metabolic phenotype (P=0.002, 0.029, 0.032 and 0.050, respectively). Computational phenotypes were similar, with 30.9, 66 and 3.1% for slow, intermediate and rapid acetylators, respectively, among HIV-positive Nigerians and 31.2, 66.3 and 2.5% among the HIV-negative group. Overall, slow phenotypes made up 31%.. NAT2 haplotype frequencies are similar in Nigerians, irrespective of HIV status, but genotype-phenotype discordances exist.

Topics: Arylamine N-Acetyltransferase; Drug Hypersensitivity; Female; Genetic Association Studies; Haplotypes; HIV; HIV Infections; Humans; Male; Middle Aged; Nigeria; Sulfonamides; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Aged; Desensitization, Immunologic; Drug Hypersensitivity; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acetazolamide; Anti-Bacterial Agents; Carbonic Anhydrase Inhibitors; Desensitization, Immunologic; Drug Hypersensitivity; Female; Humans; Pseudotumor Cerebri; Sulfonamides; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Topics: Anti-Bacterial Agents; Australia; Cephalosporins; Clostridioides difficile; Clostridium Infections; Drug Hypersensitivity; Drug Resistance, Multiple, Bacterial; Female; Humans; Liver Transplantation; Male; Nitroimidazoles; Penicillins; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

We report a patient with AIDS who had an anaphylactic-like reaction from trimethoprim-sulfamethoxazole. Clinical suspicion of anaphylaxis should be considered in patients presenting with fever, hypotension, eosinophilia, rash, flushing or pulmonary infiltrates after initial exposure and re-exposure to the medication. This case highlights the need for healthcare professionals to be reminded of the association between this unusual antibiotic reaction resembling sepsis and HIV disease.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Anaphylaxis; Anti-Bacterial Agents; Drug Hypersensitivity; Female; Fever; Humans; Pneumonia, Pneumocystis; Transgender Persons; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Bacterial Agents; Child; Desensitization, Immunologic; Drug Hypersensitivity; Humans; Male; Skin Tests; Trimethoprim, Sulfamethoxazole Drug Combination

Sulfonamide hypersensitivity has a high incidence in HIV infection and correlates with low CD4+ counts, but the mechanisms are not understood. The aims of this study were to determine whether trimethoprim/sulfamethoxazole (TMP/SMX) led to SMX adduct formation, immunogenicity, or signs of drug hypersensitivity in SIV-infected rhesus macaques, and whether differences in antioxidants, pro-inflammatory mediators, or SMX disposition were predictive of drug immunogenicity.. Four of 9 of SIV-positive (44%), and 3 of 7 SIV negative (43%) macaques had drug-responsive T cells or antibodies to SMX. Two macaques developed facial or truncal rash; these animals had the highest levels of lymph node drug adducts. Antioxidants, pro-inflammatory mediators, and SMX metabolites were not predictive of drug immunogenicity; however, the Mamu DRB1*0401/0406/0411 genotype was significantly over-represented in immune responders.. Unlike other animal models, macaques develop an immune response, and possible rash, in response to therapeutic dosages of TMP/SMX. Studying more animals with CD4+ counts <200cells/μl, along with moderately restricted ascorbate intake to match deficiencies seen in humans, may better model the risk of SMX hypersensitivity in HIV-infection. In addition, the role of Mamu-DRB1 genotype in modeling drug hypersensitivity in retroviral infection deserves further study.

Topics: Animals; Anti-Infective Agents; Antioxidants; Ascorbic Acid; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Cytochrome-B(5) Reductase; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Hypersensitivity; Female; Glutathione; HIV Infections; Interferon-gamma; Lipopolysaccharides; Lymph Nodes; Macaca mulatta; Male; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Administration, Oral; AIDS-Related Opportunistic Infections; Antibiotic Prophylaxis; Child, Preschool; Chlorpheniramine; Desensitization, Immunologic; Drug Hypersensitivity; Female; HIV; HIV Infections; Humans; Nigeria; Prednisolone; Pruritus; Skin Tests; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Both darunavir (DRV) and trimethoprim-sulfamethoxazole (TMP-SMX) carry a sulfonamide moiety and a warning for this cross-reactivity is given in the label of DRV. The aim of this study was to investigate the potential cross-reactivity between both drugs.. Retrospective cohort study with a nested case-control study.. HIV-infected patients that received DRV-containing antiretroviral therapy at any time during the period of their HIV infection were included. Patients with no history of TMP-SMX use were excluded. The incidence of a DRV allergy, according to the Naranjo probability scale, was investigated in patients with an allergy to TMP-SMX compared with those without such an allergy. In order to identify possible risk factors associated with a DRV allergy among patients allergic to TMP-SMX, a nested case-control study was subsequently performed.. A total of 405 patients were included, of whom 79 (17.5%) had a history of allergy to TMP-SMX. A DRV allergy was seen in four patients (5.1%) with a TMP-SMX allergy compared with four (1.2%) without a TMP-SMX allergy (P = 0.05). Patients with a TMP-SMX allergy were at higher risk for a DRV allergy (odds ratio 4.29; 95% confidence interval, 1.05-17.56). No additional risk factors for a DRV allergy among patients allergic to TMP-SMX were identified in the nested case-control study.. Although DRV allergy is uncommon, making cross-reactivity with TMP-SMX a rare clinical problem, it appears to exist more often in the background of a TMP-SMX allergy.

Topics: Adult; Aged; Anti-HIV Agents; Anti-Infective Agents; Case-Control Studies; Cohort Studies; Darunavir; Drug Hypersensitivity; Drug Interactions; Female; HIV Infections; Humans; Male; Middle Aged; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Bacterial Agents; Anti-HIV Agents; Bacterial Infections; Darunavir; Drug Hypersensitivity; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; HIV Infections; Humans; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Desensitization, Immunologic; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Hypersensitivity; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

Reactivation of certain latent viruses has been linked with a more severe course of drug-induced hypersensitivity reaction (HSR). For example, reactivation of human herpes virus (HHV)-6 is associated with severe organ involvement and a prolonged course of disease. The present study discusses an HSR developed in a previously healthy male exposed to ceftriaxone, doxycycline, vancomycin, and trimethoprim/sulfamethoxazole (co-trimoxazole; TMP/SMX). Initially, the patient presented clinical manifestations of HSR, as well as clinical and laboratory measurements compatible with liver and renal failure. Moreover, the patient presented skin desquamation compatible with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis. During the reaction, it was observed HHV-6 reactivation. The severity of clinical symptoms is correlated with HHV-6 titer, as well as with results of the in vitro lymphocyte toxicity assay (LTA). Serum levels of a large panel of cytokines are compared between the patient, a large population of SJS patients, and a cohort of healthy controls, using data collected by our laboratory over the years. HHV-6 was measured in the cell culture media from lymphocytes incubated with each of the 4 drugs. Moreover, we describe a new assay using cytokines released by patient lymphocytes following in vitro exposure to the incriminated drugs as biomarkers of HSR. Based on LTA results, HHV-6 reactivation and cytokine measurements, we establish that only doxycycline and TMP/SMX were involved in the HSR. As result of this analysis, the patient could continue to use the other 2 antibiotics safely.

Topics: Anti-Bacterial Agents; Chemical and Drug Induced Liver Injury; Cytokines; Doxycycline; Drug Eruptions; Drug Hypersensitivity; Herpesvirus 6, Human; Humans; Lymphocytes; Male; Roseolovirus Infections; Stevens-Johnson Syndrome; Translational Research, Biomedical; Trimethoprim, Sulfamethoxazole Drug Combination; Virus Activation; Young Adult

Patients with haematologic malignancies have a reportedly high incidence of sulfamethoxazole (SMX) hypersensitivity. The objective of this study was to determine whether deficiencies in sulfonamide detoxification pathways, to include glutathione (GSH) and ascorbate (AA), and cytochrome b(5) (b5) and cytochrome b(5) reductase (b5R), were prevalent in these patients. A secondary pilot objective was to determine whether the incidence of drug hypersensitivity following intermittent trimethoprim-SMX (TMP-SMX) prophylaxis approached that reported for high dose daily regimens.. Forty adult patients with haematologic malignancies (HM) and 35 healthy adults were studied; an additional 13 HM patients taking ascorbate supplements (HM-AA) were also evaluated. Twenty-two of 40 HM patients were prescribed and were compliant with TMP-SMX 960 mg three to four times weekly.. There were no significant differences between HM and healthy groups in plasma AA (median 37.2 µm vs. 33.9 µm) or red blood cell GSH (1.9 mmvs. 1.8 mm). However, plasma AA was correlated significantly with leucocyte b5/b5R reduction (r= 0.39, P= 0.002). Deficient b5/b5R activities were not found in HM patients. In fact, patients with chronic lymphocytic leukaemia or myeloma had significantly higher median activities (80.7 µmol mg(-1) min(-1)) than controls (18.9 µmol mg(-1) min(-1), P= 0.008). After 3-4 weeks of treatment, no patients developed SMX-specific T cells and only one patient developed rash.. Deficiencies of blood antioxidants and b5/b5R reduction were not found in this population with haematologic malignancies, and the development of skin rash and drug-specific T cells appeared to be uncommon with intermittent TMP-SMX prophylaxis.

Topics: Adult; Aged; Anti-Infective Agents; Ascorbic Acid; Case-Control Studies; Cell Proliferation; Cytochrome-B(5) Reductase; Dose-Response Relationship, Drug; Drug Hypersensitivity; Female; Glutathione; Hematologic Neoplasms; Humans; Inactivation, Metabolic; Male; Middle Aged; Statistics as Topic; Sulfamethoxazole; Sulfonamides; T-Lymphocytes; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Pneumocystis jiroveci is an important cause of mortality and morbidity among heart transplant recipients. This raises the question of prophylactic treatment for this infection. Trimethoprimsulfamethoxazole is commonly used in P. jiroveci pneumonia prophylaxis with mild to severe adverse effects. We present the use of inhaled pentamidine as P. jiroveci prophylaxis in a patient with an allergy to trimethoprim sulfamethoxazole.

Topics: Administration, Inhalation; Anti-Infective Agents; Antifungal Agents; Drug Administration Schedule; Drug Hypersensitivity; Heart Transplantation; Humans; Male; Middle Aged; Pentamidine; Pneumocystis carinii; Pneumonia, Pneumocystis; Premedication; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

In some patterns of cutaneous adverse drug reactions, and depending on the culprit drug, patch testing has been helpful in confirming its cause. Its value in Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) has not been established in a large cohort of patients.. The aim of the present study is to evaluate the safety and usefulness of patch testing in DRESS.. Between January 1998 and December 2008, we studied 56 patients with DRESS induced by antiepileptic agents in 33 patients (59%), allopurinol in 19 (34%) and sulfasalazine, cotrimoxazole, tenoxicam, and amoxicillin in 1 patient each (7%).. A positive patch test reaction was observed in 18 patients (32.1%), of which 17 were with antiepileptics and 1 with tenoxicam. In the antiepileptic group, carbamazepine alone was responsible for 13 of 17 positive reactions (76.5%). Patch tests with allopurinol and its metabolite were negative in all cases attributed to this drug.. In this study, patch testing was a safe and useful method in confirming the culprit drug in DRESS induced by antiepileptic drugs, whereas it had no value in DRESS induced by allopurinol. The pathogenesis of DRESS is not yet entirely clarified, but positive patch tests suggest a drug-dependent delayed hypersensitivity mechanism.

Topics: Allopurinol; Amoxicillin; Anticonvulsants; Drug Hypersensitivity; Eosinophilia; Exanthema; Female; Humans; Male; Middle Aged; Patch Tests; Sulfasalazine; Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Due to the escalating rates of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infection, trimethoprim-sulfamethoxazole (TMP-SMX) is being used increasingly in the pediatric population for skin and soft tissue infections. Although this combination agent has been associated with a hypersensitivity syndrome involving cutaneous skin eruptions, pediatric cases of TMP-SMX-induced hepatotoxicity are rare. We describe a relatively healthy, 9-year-old boy who developed a CA-MRSA skin and soft tissue infection and was treated with TMP-SMX. After 14 days of therapy, he was taken to the emergency department with a 3-day history of fever, headache, and neck pain. He was diagnosed with a viral syndrome, acetaminophen was prescribed, and he was sent home. Three days later, the patient returned to the emergency department with fever, vomiting, decreased energy and appetitie, and suprapubic abdominal pain, and he was hospitalized. Laboratory test results revealed elevated liver function test values. After other potential causes of liver toxicity were excluded, TMP-SMX was determined to be the cause of his acute liver toxicity. The drug was discontinued, his symptoms resolved, and his liver function tests returned to normal. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 5) between the patient's development of hepatotoxicity and the TMP-SMX therapy. This rare adverse reaction to TMP-SMX has been reported in adults; however, to our knowledge, it has been reported in only five other children. Due to the increasing use of TMP-SMX in children, clinicians should be aware of this potentially life-threatening, immunemediated hypersensitivity reaction. Fortunately, however, the hepatotoxicity appears to resolve after discontinuation of the TMP-SMX therapy in most reported cases. This case report illustrates the importance of early detection of drug-induced hepatotoxicity and timely drug discontinuation to prevent the need for liver transplantation.

Topics: Anti-Bacterial Agents; Chemical and Drug Induced Liver Injury; Child; Drug Hypersensitivity; Early Diagnosis; Eosinophilia; Humans; Liver; Male; Methicillin-Resistant Staphylococcus aureus; Staphylococcal Infections; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

We report on a patient with Pneumocystis jirovecii pneumonia who developed fever, rash, eosinophilia and hepatitis 10 days after initiation of a therapy with sulfamethoxazole and trimethoprim. A DRESS syndrome was diagnosed and the therapy was changed successfully to pyrimethamine and dapsone. We describe the clinical picture, causative drugs, pathogenesis, differential diagnoses and therapy of this life-threatening disease to acquaint the general practitioner with it.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Diagnosis, Differential; Doxorubicin; Drug Eruptions; Drug Hypersensitivity; Eosinophilia; Exanthema; Fever of Unknown Origin; Humans; Liver Function Tests; Lymphoma, T-Cell; Male; Middle Aged; Opportunistic Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Prednisone; Rituximab; Trimethoprim, Sulfamethoxazole Drug Combination; Vincristine

Sulfamethoxazole in combination with trimethoprim (cotrimoxazole) is used for prophylaxis and treatment of several opportunistic infections in HIV-infected patients. It is associated with a high incidence of hypersensitivity reactions, which is thought to have an immune basis. Genetic polymorphisms in MHC are known to predispose to hypersensitivity reactions to a structurally diverse group of drugs in HIV-positive patients. The aim of the study was to determine whether functional polymorphisms in TNF, LTA, HSPA1L and HLA-DRB1 genes influence the risk of cotrimoxazole hypersensitivity in HIV-infected patients.. We genotyped 136 HIV-positive patients with (n = 53) and without (n = 83) cotrimoxazole hypersensitivity using a combination of PCR-based techniques, including PCR-restriction fragment length polymorphisms, PCR-sequence specific oligonucleotides and real-time PCR. Genotypes and the haplotype frequencies were analyzed using the chi(2) test in the Haploview and CLUMP programs.. No statistically significant difference in SNP or haplotype frequencies were found in HIV-infected sulfamethoxazole hypersensitive patients compared with controls.. Our data show that MHC polymorphisms are not major predisposing factors for cotrimoxazole hypersensitivity, although we cannot exclude a minor contribution. An environmental factor (i.e., HIV infection) seems to predominate over any of the genetic factors so far investigated in increasing the risk of cotrimoxazole hypersensitivity.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Drug Hypersensitivity; Female; Haplotypes; HLA-DR Antigens; HLA-DRB1 Chains; HSP70 Heat-Shock Proteins; Humans; Lymphotoxin-alpha; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Trimethoprim, Sulfamethoxazole Drug Combination; Tumor Necrosis Factor-alpha

Topics: Chemical and Drug Induced Liver Injury; Child, Preschool; Diagnosis, Differential; Drug Hypersensitivity; Exanthema; Humans; Male; Mucocutaneous Lymph Node Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Drug-induced hypersensitivity syndrome (DIHS) is characterized by a severe multiorgan hypersensitivity reaction that usually appears after prolonged exposure to certain drugs and may be related to reactivation of herpes viruses. There have been few reports regarding the clinical association of DIHS with pathogens other than herpes viruses.. We report a case of scleroderma with DIHS associated with paramyxovirus infection. A 61-year-old man with early diffuse cutaneous scleroderma with myositis and progressive interstitial pneumonia developed generalized erythema with high fever 3 weeks after taking sulfamethoxazole/trimethoprim. The diagnosis of DIHS was made based on the patient's history of using an offending drug, clinical manifestations and laboratory data showing peripheral eosinophilia with the presence of atypical lymphocytes. Virological tests showed significant increases of antibody titers against mumps virus and parainfluenza virus type 2, which strongly suggested that paramyxovirus infection occurred during the clinical course of DIHS.. These findings suggest that paramyxovirus infection had contributed to the development of DIHS in this patient and that there is a need to seek evidence of other viral infections in some cases of DIHS, especially those without herpes virus reactivation/infection.

Topics: Anti-Inflammatory Agents; Antibodies, Viral; Drug Hypersensitivity; Humans; Male; Methylprednisolone; Middle Aged; Parainfluenza Virus 2, Human; Paramyxoviridae Infections; Scleroderma, Diffuse; Trimethoprim, Sulfamethoxazole Drug Combination

Adverse skin reactions to drugs are frequent, with rates of reaction to many commonly used drugs exceeding 1%. We describe a 29-year-old woman admitted with a history of itching, rash, vesicles on her hands and soles, and edema on her tongue and oropharynx after trimethoprim-sulfamethoxazole, ciprofloxacin, methenamine anhydromethylene citrate, piroxicam, azithromycin, and ceftriaxone intake. Erythema multiforme (EM) was diagnosed by skin biopsy after oral challenge with piroxicam. EM lesions reappeared after oral challenge with levofloxacin. Although EM is quite common with trimethoprim-sulfamethoxazole and there are some reports of EM appearing after intake of ciprofloxacin, it has rarely been attributed to piroxicam and no reports have identified levofloxacin as a cause.

Topics: Adult; Anti-Infective Agents; Anti-Inflammatory Agents, Non-Steroidal; Azithromycin; Ceftriaxone; Ciprofloxacin; Drug Hypersensitivity; Erythema Multiforme; Female; Humans; Levofloxacin; Methenamine; Ofloxacin; Piroxicam; Skin Tests; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

To characterize patient-reported sulfonamide allergies, assess the influence of these allergies on drug prescribing practices, and determine the frequency and nature of adverse reactions in patients with sulfonamide allergies who receive potentially cross-reactive drugs.. Prospective observational study.. Tertiary care hospital.. Ninety-four hospitalized adult patients with reported sulfonamide allergies.. Patients were followed during their hospital stay to document prescribing of and adverse reactions to sulfonamide antibiotics and sulfonamide nonantibiotics. Allergy characteristics and prescribing of sulfonamide-containing drugs were analyzed with descriptive statistics. Trimethoprim-sulfamethoxazole (TMP-SMX) allergy was reported by 42 patients (45%), whereas 42 patients (45%) did not recall the drug to which they were allergic. Fifty-nine patients (63%) reported the allergy's physical manifestation as rash, 13 (14%) anaphylaxis, and 2 (2)% Stevens-Johnson's syndrome. Median time since last reported allergic reaction to a sulfonamide-containing agent was 20 years. Forty patients (43%) had been taking a sulfonamide nonantibiotic as an outpatient for an average of 6.2 years; 24 (60%) of those patients took furosemide. Sixteen (40%) of the patients receiving sulfonamide nonantibiotics reported an allergy to TMP-SMX. Nine patients (10%) with no past sulfonamide nonantibiotic use received a sulfonamide nonantibiotic as an inpatient, with furosemide most commonly prescribed. No adverse events were reported before admission or observed during the inpatient stay (range 2-23 days).. Inpatient and outpatient use of potentially cross-reactive drugs was observed in 52% of patients, although numerous patients were unable to give an accurate allergy history. No adverse effects were reported or documented with outpatient or inpatient sulfonamide nonantibiotic use, even among patients with histories of life-threatening reactions to sulfonamides.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Colorado; Drug Hypersensitivity; Drug Interactions; Drug Prescriptions; Drug Utilization Review; Female; Hospitalization; Hospitals, University; Humans; Interviews as Topic; Male; Middle Aged; Prospective Studies; Risk Assessment; Risk Factors; Sulfonamides; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Human herpesvirus 6 (HHV-6), the causative agent of the common exanthem subitum, is a known cause of central nervous system infection in immunocompromised patients. It has been suggested that HHV-6 participate in the development of drug-induced hypersensitivity syndrome.. We reported a case of HHV-6 encephalitis associated with hypersensitivity syndrome induced by trimethoprim-sulfamethoxazole in a 72-year-old HIV-negative woman.. Our case confirmed that reactivation of HHV-6 infection may contribute to the development of the hypersensitivity syndrome.

Topics: Aged; Anti-Infective Agents; Antiviral Agents; Drug Hypersensitivity; Encephalitis, Viral; Female; Ganciclovir; Herpesvirus 6, Human; Humans; Roseolovirus Infections; Syndrome; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Sulphonamide antimicrobials, such as sulphamethoxazole (SMX), provide effective infection prophylaxis in immunocompromised patients, but can lead to drug hypersensitivity (HS) reactions. These reactions also occur in dogs, with a similar time course and clinical presentation as seen in humans.. Drug-serum adducts and anti-drug antibodies have been identified in sulphonamide HS humans. The aim of this study was to determine whether similar markers were present in dogs with sulphonamide HS.. Thirty-four privately owned sulphonamide HS dogs, 10 sulphonamide-'tolerant' dogs, 18 sulphonamide-naïve dogs, and four dogs experimentally dosed with SMX and the oxidative metabolite SMX-nitroso, were tested for drug-serum adducts by immunoblotting, and anti-drug antibodies by ELISA.. Sulphonamide-serum adducts were found in 10/20 HS dogs tested (50%), but in no tolerant dogs. Anti-sulphonamide IgG antibodies were detected in 17/34 HS dogs (50%), but in only one tolerant dog; antibody absorbance values were significantly higher in HS dogs. There was a significant association between the presence of sulphonamide-serum adducts and anti-sulphonamide antibodies (P = 0.009). Anti-drug antibodies were also found in dogs experimentally dosed with SMX-nitroso followed by SMX, but not in a dog dosed with drug vehicle, followed by SMX.. Similar humoral markers are present in dogs and humans with sulphonamide HS, supporting the use of dogs as a naturally occurring model for this syndrome in humans. These data suggest the potential use of drug-serum adducts and anti-drug antibodies as markers for sulphonamide HS. Preliminary data indicate that anti-sulphonamide antibodies may be triggered by the SMX-nitroso metabolite, not by the parent drug, in dogs.

Topics: Animals; Anti-Infective Agents; Antibody Specificity; Blood Proteins; Cross Reactions; Disease Models, Animal; Dogs; Drug Hypersensitivity; Enzyme-Linked Immunosorbent Assay; Female; Immunoglobulin G; Male; Protein Binding; Sulfamethoxazole; Sulfonamides; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acetamides; Ampicillin; Anti-Bacterial Agents; Brain Abscess; Drug Hypersensitivity; Drug Therapy, Combination; Humans; Linezolid; Listeriosis; Male; Middle Aged; Oxazolidinones; Rifampin; Trimethoprim, Sulfamethoxazole Drug Combination

Cervical lymphadenitis and fever are common in patients presenting to the Emergency Department (ED). Kikuchi's disease is a rare, self-limited cause of fever and cervical lymphadenitis often misdiagnosed as lymphoma or lupus and inappropriately treated, potentially causing numerous ED visits for unrelieved symptoms. The case described is that of a 29-year-old with persistent fever and cervical lymphadenitis who presented to the ED with a suspected allergic reaction to an antibiotic. The diagnosis of Kikuchi's disease was made in association with nasopharyngeal carcinoma and partial hydatidiform mole. The case highlights the clinical features, diagnosis, and treatment of Kikuchi's disease.

Topics: Adult; Diagnosis, Differential; Dilatation and Curettage; Drug Hypersensitivity; Emergency Medicine; Female; Fever; Histiocytic Necrotizing Lymphadenitis; Humans; Hydatidiform Mole; Nasopharyngeal Neoplasms; Neck; Pregnancy; Remission, Spontaneous; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Ultrasonography

Topics: Anti-Infective Agents; Desensitization, Immunologic; Drug Hypersensitivity; Humans; Machado-Joseph Disease; Male; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination

6 cases with pathognomonic fundus pathologies are presented and discussed using multiple-choice questions.

Topics: Adult; Aged; Albinism, Oculocutaneous; Choroid; Choroid Hemorrhage; Clindamycin; Diagnosis, Differential; Drug Hypersensitivity; Eye Diseases; Female; Fluorescein Angiography; Fundus Oculi; Humans; Male; Pigment Epithelium of Eye; Retinal Necrosis Syndrome, Acute; Toxoplasmosis, Ocular; Trimethoprim, Sulfamethoxazole Drug Combination; Vasculitis

Topics: Anemia, Refractory, with Excess of Blasts; Anti-Infective Agents; Child; Desensitization, Immunologic; Drug Hypersensitivity; Graft Rejection; Hematopoietic Stem Cell Transplantation; Humans; Male; Transplantation, Homologous; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole is a commonly used medication. Side effects are numerous and include drug hypersensitivity syndrome. The case of a 24-year-old woman with severe liver failure is presented. Erythema multiforme and thrombocytopenia developed after the acute onset of hepatotoxicity and after all medications had been stopped. Clinical resolution of all features occurred over weeks but laboratory abnormalities persisted up to eight months later. A causal link with sulfamethoxazole was supported by timing, liver biopsy and lymphocyte toxicity test. This case illustrates one presentation and the possible severity of the drug hypersensitivity syndrome associated with trimethoprim-sulfamethoxazole.

Topics: Adult; Anti-Infective Agents; Diagnosis, Differential; Drug Hypersensitivity; Erythema Multiforme; Hepatitis A; Humans; Liver Failure; Male; Syndrome; Thrombocytopenia; Trimethoprim, Sulfamethoxazole Drug Combination

Patients infected with the human immunodeficiency virus (HIV) are at higher risk for adverse drug reactions from trimethoprim-sulfamethoxazole (TMP-SMX) than the HIV-negative population. Studying the HIV-positive population the authors aimed to validate the predictive and diagnostic value of the lymphocyte toxicity assay (LTA) for adverse drug reactions. Patient lymphocytes were analyzed for toxicity to SMX and TMP. Of 35 enrolled HIV patients, 18 had TMP-SMX hypersensitivity syndrome reaction (HSR); 10 tolerated the drug; and 5 had never received the drug. When cases with HSR were compared with controls that tolerated the drugs, cytotoxicity was higher for cases: 29.5% +/- 10.1% versus 19.3% +/- 11.2% for SMX (P < 0.022) and 25.0% +/- 11.9% versus 16.3% +/- 11.0% for TMP (P < 0.04). The authors' proposed threshold value for assigning positive results for TMP and SMX hypersensitivities was 22.5%. The LTA has a strong potential for use as a diagnostic tool to assess TMP-SMX hypersensitivity in HIV-infected individuals. Larger patient populations, as well as in vitro studies are needed to further address the reasons for elevated results in immunocompromised patients and to validate the usefulness of the test.

Topics: Adult; Anti-Infective Agents; Cell Survival; Drug Hypersensitivity; Drug Monitoring; Female; HIV Infections; Humans; In Vitro Techniques; Indicators and Reagents; Lymphocytes; Male; Middle Aged; Retrospective Studies; Sulfonamides; Trimethoprim, Sulfamethoxazole Drug Combination

The clinical manifestation of human infections with Pasteurella multocida is most often cellulitis and this pathogen rarely causes septicaemia. We describe 2 Swedish patients with P. multocida septicaemia who were admitted to the same ward within the space of 7 months.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Drug Hypersensitivity; Female; Humans; Middle Aged; Pasteurella Infections; Pasteurella multocida; Penicillin G; Penicillins; Sepsis; Sweden; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Drug Hypersensitivity; Female; Hematologic Diseases; Humans; Middle Aged; Phagocytosis; Teicoplanin; Trimethoprim, Sulfamethoxazole Drug Combination

Adverse reactions to sulfonamides occur at a higher frequency in patients infected with the human immunodeficiency virus (HIV) than noninfected patients. Some studies have suggested that patients with the slow acetylator phenotype are predisposed to these reactions, whereas other studies suggest that the slow acetylator genotype is not a predisposing factor. To rationalize these seemingly contradictory observations, the authors determined the N-acetyltransferase 2 (NAT2) genotype and phenotype in patients with and without a history of hypersensitivity reactions to sulfonamides. HIV-infected patients with a history of a delayed-type hypersensitivity reaction to trimethoprim-sulfamethoxazole were enrolled, along with a group of AIDS patients with no history of hypersensitivity (delayed or immediate). NAT2 phenotype was determined in both groups using dapsone, while the genotype was determined using a polymerase chain reaction-restriction fragment length polymorphism assay. Ten of 14 patients (71%) with a history of hypersensitivity exhibited the slow acetylator phenotype, while 8 of 14 patients (57%) without such a history exhibited this same phenotype (odds ratio [OR] = 1.9, 95% confidence interval [CI] = 0.4-9.0; p = 0.69, Fisher's Exact Test). While 9 of 14 patients (64%) with a history of hypersensitivity exhibited a slow acetylator genotype, only 4 of 14 patients (29%) without such a history exhibited this genotype (ns). There were more instances of discordance between deduced and actual phenotype in the nonhypersensitive patients (n = 4) than in the hypersensitive patients (n = 1). The reported higher frequency of the slow acetylator phenotype among patients with a history of hypersensitivity to sulfonamides does not appear to be explained by metabolic changes that would cause discordance between acetylator genotype and phenotype.

Topics: Acetylation; Adult; Anti-Infective Agents; Arylamine N-Acetyltransferase; Drug Hypersensitivity; Female; Genotype; HIV Infections; Humans; Male; Middle Aged; Phenotype; Trimethoprim, Sulfamethoxazole Drug Combination

A 69-y-old woman with bioprosthetic endocarditis due to Listeria monocytogenes developed an allergic reaction after beginning ampicillin treatment. She was cured with the combination of trimethoprim-sulfamethoxazole, rifampicin and teicoplanin. No immune deficiency was found in the patient.

Topics: Aged; Anti-Bacterial Agents; Drug Hypersensitivity; Drug Therapy, Combination; Endocarditis, Bacterial; Female; Humans; Listeria monocytogenes; Listeriosis; Penicillins; Prosthesis-Related Infections; Rifampin; Teicoplanin; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

A rare sepsis-like hypersensitivity reaction has been observed in persons with human immunodeficiency virus (HIV) after exposure to trimethoprim-sulfamethoxazole. This reaction most commonly occurs on rechallenge with the drug and is manifested by a syndrome resembling bacterial sepsis. The mechanism of this unusual reaction remains unclear. We describe the first case in which this severe hypersensitivity reaction was the initial manifestation of HIV.

Topics: Adult; Anti-Infective Agents; Diagnosis, Differential; Drug Hypersensitivity; HIV Infections; Humans; Male; Sepsis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Drug Hypersensitivity; Follow-Up Studies; HIV Infections; Humans; Immune Tolerance; Pneumocystis Infections; Therapeutic Equivalency; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Anti-Infective Agents; Desensitization, Immunologic; Drug Administration Schedule; Drug Hypersensitivity; Female; Humans; Pregnancy; Pregnancy Complications; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

Hypersensitivity from trimethoprim/sulfamethoxazole (TMP/SMX) has been linked to a reactive nitroso intermediate from sulfamethoxazole metabolism, which may be altered in patients with human immunodeficiency virus (HIV) infection. The authors determined the clinical factors that are associated with TMP/SMX hypersensitivity in patients with HIV. In a case control study, 54 controls currently tolerating TMP/SMX prophylaxis were randomly matched by date of hypersensitivity reaction in case patients to 28 patients with a history of a rash consistent with erythema multiforme from TMP/SMX. Demographic data, coadministered medications, laboratory data, and histories of opportunistic infections were extracted on all patients. A highly significant association was observed between the number of opportunistic infections and the occurrence of TMP/SMX hypersensitivity (p < 0.001), despite comparability of CD4 counts between case patients and controls (p > 0.1). A tendency for protection from TMP/SMX hypersensitivity in blacks was also observed (p = 0.066). These observations suggest that the mechanisms by which HIV produces cellular immune dysfunction and alters drug detoxification may be linked.

Topics: Adolescent; Adult; Aged; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Case-Control Studies; Drug Hypersensitivity; Female; HIV Infections; Humans; Male; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination

To establish the safety and efficacy of desensitization to co-trimoxazole in hypersensitive HIV-infected subjects. To assess if delayed hypersensitivity (type IV) to co-trimoxazole predicts those unable to be desensitized.. desensitization to co-trimoxazole, comprising trimethoprim (T) 0.4 mg and sulphamethoxazole (S) 2 mg initially with doubling dose daily, full strength co-trimoxazole (T/S 160 mg/800 mg) at 10 days. Patch testing with 4.5% and 9% co-trimoxazole in yellow soft paraffin, CMI Multitest.. nineteen patients, 18 male and one female, were recruited and completed the desensitization regime. Of these 80%(15) achieved successful desensitization. Three of those who reacted did so within 18 days. All patients were successfully managed in an outpatient setting. There were no major adverse reactions. Of those reacting none gave a positive patch test to co-trimoxazole and all showed absent delayed type hypersensitivity reactions to recall antigens.. co-trimoxazole desensitization is a safe and efficacious procedure, with a success rate of 80% using the above regime. Patch testing with co-trimoxazole gives no useful information about those that reacted.

Topics: Adult; Anti-Infective Agents; Desensitization, Immunologic; Drug Hypersensitivity; Female; HIV Infections; Humans; Hypersensitivity, Delayed; Male; Outpatients; Patch Tests; Pneumonia, Pneumocystis; Predictive Value of Tests; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents, Urinary; Antirheumatic Agents; Arthritis, Rheumatoid; Drug Hypersensitivity; Humans; Male; Methotrexate; Middle Aged; Pancytopenia; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-associated systemic reactions, including aseptic meningitis, have been reported to be very rare adverse drug reactions. Patients with Sjögren's syndrome have been overrepresented, but no epidemiological surveys of the reaction have been conducted. To study the overall frequency of adverse drug reactions, and especially trimethoprim-associated reactions, we interviewed 85 primary Sjögren's syndrome patients and compared the results with those of 45 similarly interviewed osteoarthritis patients. Antimicrobial allergy was more common among Sjögren's syndrome patients than in osteoarthritis patients (46% vs. 27%). Eleven Sjögren's syndrome patients (13%), but no osteoarthritis patient, had experienced at least a partial, non-allergic systemic reaction with trimethoprim. Of them five (6%) had had a full-blown systemic reaction including both chills/fever and headache/backache and at least one of the following: malaise, vomiting, dizziness, confusion or meningeal irritation. Our findings confirm that allergic reactions to antimicrobials are frequent in Sjögren's syndrome. In addition to allergic reactions Sjögren's syndrome patients are prone to a specific trimethoprim-associated systemic reaction. This should be remembered when prescribing antimicrobials.

Topics: Adult; Aged; Antimalarials; Autoimmune Diseases; Drug Hypersensitivity; Female; Health Surveys; Humans; Interviews as Topic; Male; Middle Aged; Sjogren's Syndrome; Surveys and Questionnaires; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; China; Drug Eruptions; Drug Hypersensitivity; Female; HIV Infections; Humans; Malaysia; Male; Middle Aged; Pneumonia, Pneumocystis; Retrospective Studies; Scotland; Trimethoprim, Sulfamethoxazole Drug Combination; White People

Bactrim/Septra is a drug used for treating and preventing PCP (Pneumocystis carinii pneumonia) and toxoplasmosis. However, people with HIV are more likely to develop hypersensitivity reactions to Bactrim/Septra. NAC (N-acetyl-cysteine) is being studied to determine if its detoxifying properties could reduce the risk of hypersensitivity to Bactrim/Septra. However, a Canadian study found no statistically significant difference in the rates of hypersensitivity among the nearly 200 subjects.

Topics: Acetylcysteine; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Drug Hypersensitivity; Free Radical Scavengers; Humans; Pneumonia, Pneumocystis; Primary Prevention; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Antifungal Agents; CD4 Lymphocyte Count; Drug Hypersensitivity; Humans; Immunosuppressive Agents; Pneumonia, Pneumocystis; Skin; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antidotes; Drug Hypersensitivity; Glutathione; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Anti-Infective Agents; Child, Preschool; Drug Hypersensitivity; Female; Humans; India; Male; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Adult; Anti-Infective Agents; Drug Hypersensitivity; Humans; Male; Middle Aged; Skin Tests; Trimethoprim, Sulfamethoxazole Drug Combination

Hypersensitivity reactions to trimethoprim-sulfamethoxazole (TMP-SMX) are very common in HIV-infected patients, leading to drug discontinuation. However, it is the drug of choice as prophylaxis for Pneumocystis carinii pneumonia.. We sought to determine the safety and long-term efficacy of a 6-hour TMP-SMX-graded challenge in a group of hypersensitive HIV-infected patients.. Forty-four consecutive HIV-infected patients with documented TMP-SMX hypersensitivity were seen in our outpatient allergy department. They ingested 12 doses of increasing amounts of TMP-SMX at half-hour intervals. Thereafter, they took 80/400 mg TMP-SMX daily and were advised to "treat through" every nonbullous cutaneous adverse reaction.. All 44 patients tolerated the procedure without any adverse reactions during the day of challenge. Eleven of the 44 patients experienced mild hypersensitivity reactions on days 1 to 2 (8 patients) and 8 to 10 (3 patients), consisting mainly on a 1-day pruritic maculopapular eruption. Two patients stopped TMP-SMX at day 1, and 2 stopped it at days 10 and 15, giving an overall success rate at 1 month of 91% (40 of 44). Two were successfully rechallenged late. After a median follow-up of 10 months, 42 patients were taking TMP-SMX without any adverse reaction, giving an overall success rate of 95%.. A 6-hour graded challenge with cautious "treating through" of mild reactions enables more patients to take TMP-SMX and is safe and effective.

Topics: Administration, Oral; Adult; Drug Administration Schedule; Drug Hypersensitivity; Female; HIV Infections; Humans; Male; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

To report a case of successful desensitization to dapsone for Pneumocystis carinii pneumonia (PCP) prophylaxis in a patient unable to tolerate trimethoprim/sulfamethoxazole (TMP/SMX) desensitization or dapsone at standard doses.. A 37-year-old HIV-positive African-American man was treated for pneumonia with TMP/SMX and then continued on the drug for PCP prophylaxis. After experiencing a pruritic maculopapular rash with TMP/SMX, both at standard doses and after attempting a desensitization regimen to the drug, he was started on dapsone for PCP prophylaxis. He experienced a rash and fever after taking dapsone at standard PCP prophylactic doses. At this time, an 18-day oral dapsone rechallenge by dose escalation was attempted, and it was well tolerated.. This case suggests that utilization of a dapsone desensitization regimen may permit a viable treatment option in patients previously thought to be intolerant to the agent. More regimens of this type should be attempted and the results published, using both dapsone and TMP/SMX, so that standard desensitization treatment guidelines may eventually be adopted.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Dapsone; Desensitization, Immunologic; Drug Hypersensitivity; HIV Seropositivity; Humans; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

The diagnosis of a drug allergy is mainly based upon a very detailed history and the clinical findings. In addition, several in vitro or in vivo tests can be performed to demonstrate a sensitization to a certain drug. One of the in vitro tests is the lymphocyte transformation test (LTT), which can reveal a sensitization of T-cells by an enhanced proliferative response of peripheral blood mononuclear cells to a certain drug.. To evaluate the sensitivity and specificity of the LTT, 923 case histories of patients with suspected drug allergy in whom a LTT was performed were retrospectively analysed.. Based on the history and provocation tests, the probability (P) of a drug allergy was estimated to be > 0.9, 0.5-0.9, 0.1-0.5 or < 0.1, and was put in relation to a positive or negative LTT.. Seventy-eight of 100 patients with a very likely drug allergy (P > 0.9) had a positive LTT, which indicates a sensitivity of 78%. If allergies to betalactam-antibiotics were analysed separately, the sensitivity was 74.4%. Fifteen of 102 patients where a classical drug allergy could be excluded (P < 0.1), had nevertheless a positive LTT (specificity thus 85%). The majority of these cases were classified as so-called pseudo-allergic reaction to NSAIDs. Patients with a clear history and clinical findings for a cotrimoxazole-related allergy, all had a positive LTT (6/6), and in patients who reacted to drugs containing proteins, sensitization could be demonstrated as well (i.e. hen's egg lysozyme, 7/7). In 632 of the 923 cases, skin tests were also performed (scratch and/or epicutaneous), for which we found a lower sensitivity than for the LTT (64%), while the specificity was the same (85%).. Although our data are somewhat biased by the high number of penicillin allergies and cannot be generalized to drug allergies caused by other compounds, we conclude that the LTT is a useful diagnostic test in drug allergies, able to support the diagnosis of a drug allergy and to pinpoint the relevant drug.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Drug Hypersensitivity; Humans; Lymphocyte Activation; Penicillins; Predictive Value of Tests; Pyrazoles; Pyrazolones; Sensitivity and Specificity; Skin Tests; T-Lymphocytes; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Desensitization, Immunologic; Drug Hypersensitivity; Female; Humans; Lung Transplantation; Middle Aged; Postoperative Complications; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Drug Hypersensitivity; HIV Infections; Humans; Pneumocystis Infections; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anaphylaxis; Anti-Infective Agents; Desensitization, Immunologic; Diagnosis, Differential; Drug Hypersensitivity; HIV Infections; Humans; Shock, Septic; Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

The estate of [name removed] will receive a $75,000 emotional distress award in addition to $104,109 in emotional damages from Dr. [name removed], [name removed], an infectious disease specialist. [Name removed] suffered an allergic reaction to Cotrim, a sulfa-based medicine prescribed by Dr. [name removed]. The reaction resulted in [name removed]'s hospitalization and eight months of recovery. [Name removed]'s allergy to sulfa-based drugs was noted on his chart. [Name removed]'s attorney argued that [name removed] was already in a frail emotional state and thus should not be entitled to full recovery of emotional distress damages. In 1995, the State Court of Appeals ruled that the damage award should go back to court. The Supreme Court turned down [name removed]'s request and restored the damage award.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Drug Hypersensitivity; Fluoroquinolones; Humans; Male; Malpractice; Medical Records; Oregon; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

In hospitals attended by patients with human immunodeficiency virus infection, adverse reactions are often observed to trimethoprim-sulfamethoxazole, particularly cutaneous reactions. Given the importance of this drug for prophylaxis we have attempted to establish a desensitization or tolerance protocol so that patients can continue the drug without repeated adverse reactions.. We studied 34 HIV patients with adverse cutaneous reactions to trimethoprim-sulfamethoxazole, slight to moderate in nature but not life-threatening. Skin tests (prick and intradermal) were done in an attempt to rule out a mechanism of hypersensitivity. Subsequently, trimethoprim-sulfamethoxazole was administered orally in increasing doses beginning with trimethoprim, 0.2 mg, and sulfamethoxazole, 1 mg. The same dose was repeated after 12 hours and then doubled every 24 hours until the therapeutic dose was achieved. If adverse reactions appeared we maintained the last dose administered and administered antihistamines until the reactions cleared or improved.. None of the patients had positive skin tests (immediate or delayed). Twenty- seven patients were satisfactorily desensitized. After a follow-up of 3 months, 25 patients were still incident-free on trimethoprim-sulfamethoxazole prophylaxis, and 19 returning for check-ups at 6 months could still tolerate the drug well.. Our data indicate that patients with adverse reactions to trimethoprim-sulfamethoxazole can continue prophylactic treatment after oral desensitization.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Desensitization, Immunologic; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Hypersensitivity; Drug Tolerance; Female; Humans; Male; Pneumocystis Infections; Trimethoprim, Sulfamethoxazole Drug Combination

To assess the safety of dapsone prophylaxis of Pneumocystis carinii pneumonia (PCP) in patients with prior intolerance to trimethoprim/sulfamethoxazole (TMP/SMX).. We conducted a retrospective study in the categorical human immunodeficiency virus out-patient program of a university hospital. Patients who had filled prescriptions for dapsone at our pharmacy between January 1991 and April 1994 were evaluated and 75 patients were found eligible for analysis.. The overall incidence of adverse events (AE) in our study cohort was 39%. The most common AEs were anemia (23%) and rash (16%). However, after critical evaluation of each case, only 3 cases of anemia (4%) and 2 cases of rash (3%) were judged to be "likely related" to dapsone. Only 5/75 patients (7%) developed the same intolerance to dapsone as previously experienced on TMP/SMX, and none of these cases was viewed as "likely related" to dapsone. A dapsone regimen of 100 mg qd and a prior episode of PCP were associated with a higher incidence of AEs. Eight cases of PCP occurred in spite of dapsone prophylaxis for an incidence of 7 cases per 1,000 patient-months. Seven of the cases of PCP occurred in patients who were receiving secondary prophylaxis.. Given the low incidence of AEs judged to be "likely related" to dapsone, this drug is a reasonable choice for PCP prophylaxis in patients with prior AEs to TMP/SMX.

Topics: Adult; Anti-Infective Agents; Anti-Infective Agents, Urinary; Dapsone; Dose-Response Relationship, Drug; Drug Hypersensitivity; Female; HIV Infections; Humans; Incidence; Male; Middle Aged; Pneumonia, Pneumocystis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

To determine whether HIV-infected patients have a deficiency of intracellular glutathione (GSH) in peripheral blood mononuclear cells (PBMC) and erythrocytes.. Initial experiments determining the stability of intracellular GSH preceded the measurement of GSH levels in 33 HIV-positive patients and 40 control subjects within 1 h of isolation of their blood cells. In addition, the susceptibility of erythrocytes to dapsone hydroxylamine-induced methaemoglobinaemia was evaluated.. GSH levels were determined by an high-performance liquid chromatography method utilizing a fluorescent probe, monobromobimane. The bimane-GSH adduct formed in PBMC was also characterized by mass spectrometry. Methaemoglobin formation on exposure to dapsone hydroxylamine was determined spectrophotometrically.. GSH levels remained stable for only 1 h after cell isolation, thereafter showing a decrease of 20 and 60% at 4 and 24H, respectively, There was no difference in the GSH levels in PBMC and erythrocytes of the HIV-positive patients compared with controls. The GSH levels were not related to the disease stage or to CD4+ cell counts. There was no difference in GSH levels in PBMC taken from trimethoprim-sulphamethoxazole-hypersensitive and non-hypersensitive patients. Methaemoglobinaemia on exposure of erythrocytes to dapsone hydroxylamine was concentration-dependent, but there was no significant difference between patients and controls.. In contrast to previous studies, no deficiency of intracellular GSH in the PBMC and erythrocytes of HIV-infected patients was found. The discrepancy between studies may be methodological reflecting the instability of GSH, which requires prompt sample analysis.

Topics: Adult; Aged; CD4 Lymphocyte Count; Dapsone; Drug Hypersensitivity; Erythrocytes; Glutathione; HIV Infections; Humans; Leukocytes, Mononuclear; Male; Methemoglobinemia; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination

Although trimethoprim-sulfamethoxazole is the preferred chemoprophylaxis against Pneumocystis carinii pneumonia, there are frequent IgE-mediated reactions among children infected with the human immunodeficiency virus (HIV). Oral desensitization allows more patients to receive chemoprophylaxis, but it has been studied in only a limited number of children.. We desensitized five children infected with the HIV using a rapid, 4-h oral protocol.. Three children (including two infants) successfully completed desensitization and started maintenance therapy, but the other two experienced reactions that precluded further administration of trimethoprim-sulfamethoxazole.. We conclude that a rapid, oral trimethoprim-sulfamethoxazole desensitization protocol is safe and, in some instances, effective among HIV-infected children and infants with a history of non-life-threatening, IgE-mediated reactions to trimethoprim-sulfamethoxazole.

Topics: Administration, Oral; AIDS-Related Opportunistic Infections; CD4-CD8 Ratio; Child; Child, Preschool; Desensitization, Immunologic; Drug Hypersensitivity; Female; HIV Infections; Humans; Infant; Lymphocyte Count; Male; Trimethoprim, Sulfamethoxazole Drug Combination

The records of 206 patients with advanced infection due to human immunodeficiency virus type 1 who were receiving prophylaxis with clindamycin/primaquine (C/P), trimethoprim-sulfamethoxazole (TMP-SMZ), or dapsone to prevent Pneumocystis carinii pneumonia (PCP) were retrospectively examined. Two hundred sixty-two patient-years of prophylaxis were accrued (176.2 of TMP-SMZ, 63.4 of dapsone, and 22.8 of C/P). The rates of PCP in the TMP-SMZ, dapsone, and C/P groups were 3.4, 11.0, and 30.7 per 100 patient-years, respectively. Pairwise comparisons showed C/P to be less effective than TMP-SMZ (relative risk [RR], 9.02; 95% confidence interval [CI], 3.03-26.83). A similar trend was apparent for C/P vs. dapsone (RR, 2.78; 95% CI, 0.98-7.93). When only those receiving primary prophylaxis were analyzed, C/P recipients remained at greater risk than TMP-SMZ recipients (RR, 13.19; 95% CI, 3.54-49.12) and dapsone recipients (RR, 3.85; 95% CI, 1.12-13.31). Failure of C/P prophylaxis could be due, at least in part, to underdosing (clindamycin, 300 mg/d; primaquine, 15 mg/d). C/P recipients had more nonspecific diarrhea than did TMP-SMZ recipients (RR, 2.99; 95% CI, 1.61-5.55).

Topics: Adult; Anti-Bacterial Agents; Anti-Infective Agents; Antimalarials; CD4 Lymphocyte Count; Clindamycin; Dapsone; Diarrhea; Drug Hypersensitivity; Drug Therapy, Combination; Female; Gastrointestinal Diseases; Hematologic Diseases; HIV Infections; HIV-1; Humans; Male; Pneumonia, Pneumocystis; Primaquine; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

To study the outcome of a modified oral desensitization protocol for trimethoprim-sulfamethoxazole in human immunodeficiency virus infected patients with Pneumocystis carinii pneumonia and acquired immune deficiency syndrome.. A prospective study.. Tertiary care referral center.. Thirteen human immunodeficiency virus infected patients with Pneumocystis carinii pneumonia and allergy to sulfonamides who failed alternative therapy.. Oral desensitization to trimethoprim-sulfamethoxazole.. Nature of allergic reactions, toxicity of alternate medications, indication as well as outcome of trimethoprim-sulfamethoxazole desensitization and routine laboratory determinations.. The most common reaction to trimethoprim-sulfamethoxazole was generalized, pruritic maculopapular rash (n = 10, 76.9%) followed by urticaria/angioedema in two patients (15.38%). Two patients had generalized pruritus without rash. All patients (n = 13) tolerated oral desensitization to trimethoprim-sulfamethoxazole without any adverse reactions including three patients who were critically ill and on mechanical ventilation. Thus the success rate of our protocol was 100%. No patient had received antihistamines prior to or during the protocol. Four patients (5, 6, 7, and 9) were receiving prednisone for severe Pneumocystis carinii pneumonia. Total followup has ranged from 4 to 84 weeks. Two patients died during followup due to causes unrelated to desensitization. All other patients are tolerating trimethoprim-sulfamethoxazole without any allergic reactions.. Oral desensitization to trimethoprim-sulfamethoxazole, as per this protocol is safe, in that there were no systemic or cutaneous reactions during desensitization as well as followup. It is well tolerated in all patients, including the three critically ill patients. As judged by the outcome and ability to tolerate trimethoprim-sulfamethoxazole after desensitization, the procedure is successful in all patients in this study. Equipped with this protocol one can evaluate possible mechanisms of desensitization such as oral tolerance or mediator depletion in a controlled fashion.

Topics: Administration, Oral; Adult; AIDS-Related Opportunistic Infections; Anaphylaxis; Desensitization, Immunologic; Drug Hypersensitivity; Female; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Prospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Desensitization, Immunologic; Drug Hypersensitivity; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

To measure the incidence of cutaneous hypersensitivity reactions to cotrimoxazole in the setting of primary Pneumocystis carinii pneumonia (PCP) prophylaxis: to measure the incidence of severe reactions: and to identify predictors for these outcomes.. Retrospective cohort study.. One university-based outpatient HIV clinic and one university-affiliated internal medicine and infectious disease medical practice.. Two hundred thirty-six HIV-infected individuals receiving cotrimoxazole for primary PCP prophylaxis.. None.. Occurrence of a cutaneous hypersensitivity reaction, defined as rash, fever, or pruritus that resulted in permanent discontinuation of cotrimoxazole. Severe reactions were defined as those resulting in hospital admission or systemic treatment with a corticosteroid. Cox regression was used to calculate relative rates (RRs) and 95% confidence intervals (CIs) for a number of clinical and laboratory variables.. Forty-eight (20%) subjects developed cutaneous hypersensitivity reactions, with six (12.5%) of these being severe. In the unadjusted analysis, the following factors demonstrated at least borderline association: male gender [RR (95% CI) = 0.46 (0.21-0.99)], higher CD4 percentage [RR (95% CI) = 0.95 (0.90-1.00)], syphilis history [RR (95% CI) = 0.37 (0.13-1.04)], and higher total protein [RR (95% CI) = 0.70 (0.45-1.09)]. Adjustment for potential confounding by measured variables did not meaningfully change these results.. Cutaneous hypersensitivity reactions to cotrimoxazole in the setting of primary PCP prophylaxis are common. Although male gender, higher CD4 percentage, syphilis history, and higher total protein have at least borderline associations with these reactions, routinely collected clinical and laboratory variables do not appear to be sufficiently associated with the reactions to permit development of a clinically useful prediction rule.

Topics: Adult; Aged; Anti-Infective Agents, Urinary; Antibiotic Prophylaxis; Cohort Studies; Drug Hypersensitivity; Female; HIV Infections; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

An undoubtable role of the melioidosis germ persistence in the form of L-variants with the development of DTH in the relapses of the disease was stated. Serological reactions such as CFT and PHAR were shown to be of the diagnostic value but it was by far lower than the allergotest. No correlation between the antibody titers in the tested sera and the isolation of the bacterial or L-variants of the melioidosis germ was observed. The criteria of the recovery from melioidosis were: stable normalization of the patient temperature, positive time course of the body weight changes, negative tests for the type and morphologically changed forms of the melioidosis germ and no allergic reactions.

Topics: Animals; Anti-Bacterial Agents; Burkholderia pseudomallei; Complement System Proteins; Drug Hypersensitivity; Drug Therapy, Combination; Guinea Pigs; Hypersensitivity, Delayed; Laboratories; Melioidosis; Quality Assurance, Health Care; Serologic Tests; Sulfamethoxazole; Titrimetry; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Desensitization, Immunologic; Dose-Response Relationship, Drug; Drug Hypersensitivity; HIV Infections; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

Antibody- and cell-mediated responses to sulfamethoxazole (SMX) were analyzed in AIDS patients with or without a history of hypersensitivity and in negative controls. In 20 of 20 (P < 0.01) human immunodeficiency virus (HIV)-seropositive patients with skin reactions to cotrimoxazole, we found SMX-specific antibodies, while only 9 of 20 and 17 of 20 HIV-seropositive patients without a history of hypersensitivity to cotrimoxazole had SMX-specific immunoglobulin M (IgM) and IgG, respectively. The levels of specific IgM and IgG were higher in patients with skin reactions than in patients without reactions (IgM, 1.0 +/- 0.19 versus 0.47 +/- 0.23 [P < 0.001]; IgG, 0.68 +/- 0.15 versus 0.47 +/- 0.14 [P < 0.001] [mean optical density values +/- standard deviations]). Seronegative controls with no history of exposure to sulfa compounds did not have SMX-specific IgG or IgM antibodies, and controls with a history of intake of SMX with or without reactions had low levels of IgG and IgM. The SMX-specific IgG subclasses were exclusively IgG1 and IgG3. None of the patients had detectable SMX-specific IgE or IgA antibodies nor did they exhibit a cell-mediated response as measured by a lymphocyte proliferation assay. Antibodies to SMX recognized N-acetyl-sulfonamide, N-(2-thiazolyl)-sulfanilamide, sulfadiazine, and sulfisoxazole but did not recognize sulfanilamide or 3-amino-5-methyl isoxazole in an inhibition assay. It is not known whether the SMX-specific antibodies associated with hypersensitivity reactions to SMX in HIV-seropositive patients have a pathogenic role in these reactions. Sulfanilamide or 3-amino-5-methyl isoxazole, on the other hand, could be potential alternative therapies in HIV-seropositive patients with a history of skin reactions to SMX.

Topics: Acquired Immunodeficiency Syndrome; Adult; Antibody Formation; Antibody Specificity; Drug Hypersensitivity; Haptens; Humans; Immunity, Cellular; Immunoglobulin G; Immunoglobulin M; Infant; Lymphocyte Activation; Lymphocytes; Sulfamethoxazole; Sulfonamides; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adolescent; Central Nervous System; Drug Hypersensitivity; Female; Humans; Sulfanilamides; Trimethoprim, Sulfamethoxazole Drug Combination

The term bullous drug eruption connotes several heterogeneous diseases in which blisters occur as a complication of the administration of drugs. Blisters may occur in bullous erythema multiforme, fixed drug eruption, or severe dermatitis medicamentosa with blisters. The common denominator is thought to be a hypersensitivity reaction to a systemic medication. Nevertheless, little has been written about the blisters in these disorders, and neither common nor distinct pathogenic mechanisms have been proposed. We describe a patient who had a rapidly progressive bullous eruption that occurred within hours of receiving intravenous trimethoprim-sulfamethoxazole. Routine histologic study of lesional skin demonstrated subepidermal blisters. Transmission electron microscopy and immunomapping of various basement components revealed that the cleavage plane of the blister was well below the lamina densa. After healing of the blistering process, no scarring or milia formation was observed.

Topics: Basement Membrane; Blister; Cicatrix; Drug Eruptions; Drug Hypersensitivity; Epidermis; Female; Fluorescent Antibody Technique; Humans; Microscopy, Electron; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (T/S) is an effective and important prophylactic medication for HIV-infected patients that must frequently be discontinued because of allergic reactions.. Our objective was to assess the safety, the frequency of success, and the duration of desensitization to T/S in HIV-infected patients.. We studied oral desensitization with T/S of patients with a history of allergy to the medication and longitudinal follow-up. Twenty-eight men with a history of T/S-induced skin rashes were studied. Mean age was 35 years (range, 26 to 50 years). Mean CD4 count was 89 cells/mm3 (range, 0/mm3 to 210/mm3). Patients were seen every 4 to 6 weeks. Mean follow-up was 19.07 weeks (range 2 to 81 weeks).. After 32 weeks, 23 of 28 (82%) patients were successfully desensitized (four had rashes develop, and one could not continue for personal reasons). Of the 23 patients who were successfully desensitized, six were known to have subsequently discontinued T/S (four had rashes; two discontinued on the advice of their personal primary physicians). Six patients were lost to follow-up. One patient died of pulmonary Kaposi's sarcoma. Ten patients are taking the medication regularly without any problems.. T/S desensitization is a simple, safe and effective means to provide it for most patients with a history of "allergic" rashes.

Topics: Adult; AIDS-Related Opportunistic Infections; Desensitization, Immunologic; Drug Hypersensitivity; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Drug Hypersensitivity; Expert Testimony; Fatal Outcome; Female; Humans; Malpractice; Nursing Staff, Hospital; Texas; 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

Topics: Drug Hypersensitivity; Fever; Heart Arrest; HIV Infections; Humans; Hypotension; Infant; Male; Respiratory Insufficiency; Tachycardia; Trimethoprim, Sulfamethoxazole Drug Combination

The incidence of Pneumocystis carinii pneumonia (PCP) has been shown to be high posttransplantation in the absence of prophylaxis. For this reason, lung transplant recipients routinely receive prophylaxis. We report on our results using aerosolized pentamidine prophylaxis in nine patients post-lung transplantation (eight single lung transplants, one double). The patients received monthly treatments of 300 mg of aerosolized pentamidine for a mean of 10.6 months (range, 4 to 21 months). Patients were routinely monitored with serial pulmonary function studies and bronchoscopy as clinically indicated. Two of the patients experienced bronchospasm in response to the therapy. None of the patients experienced any episodes of PCP during the period of inhaled pentamidine prophylaxis. Inhaled pentamidine is a safe and effective form of PCP prophylaxis and may be used instead of sulfamethoxazole-trimethoprim in patients who have a sulfa allergy or other untoward sulfa side effects.

Topics: Administration, Inhalation; Aerosols; Bronchial Spasm; Bronchoscopy; Drug Hypersensitivity; Forced Expiratory Volume; Graft Rejection; Humans; Immunosuppressive Agents; Lung Transplantation; Maximal Midexpiratory Flow Rate; Nebulizers and Vaporizers; Pentamidine; Pneumonia, Pneumocystis; Retrospective Studies; Spirometry; Trimethoprim, Sulfamethoxazole Drug Combination; Vital Capacity

Topics: Drug Eruptions; Drug Hypersensitivity; Humans; Infant; Lymphocytosis; Male; Sulfamethoxazole; Trimethoprim, Sulfamethoxazole Drug Combination

Typical cutaneous hypersensitivity reaction to co-trimoxazole was seen in a woman after autologous bone marrow transplantation and immunotherapy. She had developed no such reaction during chemotherapy prior to the transplant or immediately after the transplant. The immunoperturbed state that exists for a period of time after bone marrow transplantation, especially in the presence of immunomodulation caused by combined therapy with recombinant human interferon alpha and interleukin-2, with exposure to potentially reaginic agents may have contributed to the development of the hypersensitivity reaction in this patient.

Topics: Adult; Bone Marrow Transplantation; Drug Hypersensitivity; Female; Humans; Interferon-alpha; Interleukin-2; Skin; Trimethoprim, Sulfamethoxazole Drug Combination

A group of clinical, immunologic, and virologic variables was examined to determine if any predicted the development of hypersensitivity to trimethoprim-sulfamethoxazole (TMP-SMZ) during treatment of Pneumocystis carinii pneumonia in patients with human immunodeficiency virus (HIV) infection. Hypersensitivity occurred in 39 (27%) of 143 patients, who had significantly higher total lymphocyte and CD4+ and CD8+ cell counts and CD4:CD8 ratios than did those who did not develop hypersensitivity. Regression analysis identified having a CD4:CD8 ratio > 0.10 (95% confidence interval [CI], 1.75-3.94; P = .02) and treatment for < 14 days (95% CI, 1.57-3.75; P = .04) as independently predictive of hypersensitivity. Use of corticosteroids tended to reduce the frequency of hypersensitivity (7% vs. 30%; P = .07). T lymphocytes may be important in the pathogenesis of these hypersensitivity reactions. As the frequency of hypersensitivity declines with disease progression, T lymphocytes could be effector cells in these reactions or their sensitivity to TMP-SMZ may decline with HIV disease progression.

Topics: Adrenal Cortex Hormones; Adult; Aged; AIDS-Related Opportunistic Infections; Antibodies, Viral; CD4-CD8 Ratio; Cytomegalovirus Infections; Drug Hypersensitivity; Humans; Immunoglobulins; Male; Middle Aged; Pneumonia, Pneumocystis; Regression Analysis; Trimethoprim, Sulfamethoxazole Drug Combination

Hypersensitivity to trimethoprim-sulphamethoxazole (TMP-SMX) in patients with HIV infection may be a result of either immune dysregulation, a direct cytotoxicity of the SMX-hydroxylamine metabolite (SMX-HA) (rather than SMX per se), or glutathione deficiency. We evaluated the in vitro cytotoxicity of SMX and SMX-HA to peripheral blood mononuclear cells (PBMC) of HIV-infected subjects to determine if the degree of in vitro cytotoxicity is associated with hypersensitivity, whether glutathione inhibits cytotoxicity, and whether in vitro cytotoxicity is predictive for the development of hypersensitivity. Given that fever is often a prominent feature of hypersensitivity, we also assessed whether SMX or SMX-HA could induce the in vitro production of IL-1 beta, IL-6 or tumour necrosis factor-alpha (TNF-alpha) by PBMC. The cytotoxicities of SMX and SMX-HA to PBMC were assessed in 45 HIV-infected patients with prior TMP-SMX therapy, and in eight HIV- controls. Twelve HIV-infected subjects were studied prospectively before primary Pneumocystis carinii pneumonia (PCP) therapy or rechallenge with TMP-SMX in previously hypersensitive subjects. Cytokine production was measured in four hypersensitive and two non-hypersensitive HIV-infected subjects, and three HIV-uninfected controls. The cytotoxicity of SMX-HA to PBMC was significantly greater in the 22 HIV-infected patients with prior hypersensitivity than both the 23 HIV-infected patients without hypersensitivity and the control group. Cytotoxicity was significantly reduced by glutathione only in the hypersensitive group. SMX did not induce cytotoxicity in any group. In 12 subjects studied prospectively, SMX-HA cytotoxicity was also significantly greater in those with subsequent hypersensitivity. Exposure of PBMC to SMX-HA resulted in a modest increase in the production of IL-6, IL-1 beta and TNF-alpha, although no major difference was detected between subjects with or without hypersensitivity. These data suggest that SMX-HA and glutathione deficiency are involved in the pathogenesis of hypersensitivity to TMP-SMX in HIV-infected patients, and that in vitro cytotoxicity could be useful in the diagnosis of hypersensitivity and predicting its likelihood.

Topics: Adult; CD4-CD8 Ratio; Cytokines; Cytotoxicity, Immunologic; Drug Hypersensitivity; Glutathione; HIV Infections; Humans; Male; Sulfamethoxazole; Trimethoprim, Sulfamethoxazole Drug Combination

This study was undertaken to determine whether patients infected with HIV and with prior hypersensitivity to trimethoprim-sulphamethoxazole (TMP-SMX) can be rechallenged successfully with TMP-SMX, what factors predict successful rechallenge, and whether hypersensitivity is due to TMP or to SMX.. A prospective, open study.. A tertiary referral hospital.. Thirty-one HIV-infected patients with a history of non-life-threatening hypersensitivity to TMP-SMX.. Patients received TMP (300 mg twice a week) for 2 weeks and, where no major reaction occurred, subsequently with TMP-SMX (160 and 800 mg per tablet, one tablet two times a day, twice a week). Patients who developed significant and persistent hypersensitivity ceased SMX and were subsequently challenged with TMP-dapsone (300 and 100 mg, respectively, twice a week).. That rechallenge is more likely to be successful in those with advanced HIV disease.. Five out of 31 (16%) patients developed hypersensitivity to TMP, and two ceased TMP as a result. Fifteen of the 26 (58%) patients who received subsequent TMP-SMX developed hypersensitivity, 12 of whom ceased TMP-SMX because of this reaction. Hypersensitivity to TMP-SMX was significantly less common in those with a CD4+ cell count < 20 x 10(6)/l than in those with a CD4+ cell count > 20 x 10(6)/l (31 versus 85%; P = 0.03). Hypersensitivity to TMP-dapsone occurred in two out of nine patients with hypersensitivity to TMP-SMX on rechallenge. One patient developed transient dyspnoea following a dose of SMX, but no other serious adverse drug reaction occurred.. Rechallenge with TMP-SMX appears safe in HIV-infected patients with a history of non-life-threatening hypersensitivity and is most likely to be successful in patients with a low CD4+ lymphocyte count. The data suggest a low rate cross-hypersensitivity between SMX and dapsone, at least at the doses used.

Topics: Adult; AIDS-Related Opportunistic Infections; Cross Reactions; Drug Eruptions; Drug Hypersensitivity; HIV Infections; Humans; Male; Pneumocystis Infections; Safety; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Drug Hypersensitivity; HIV Infections; Humans; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Drug Hypersensitivity; HIV Infections; Humans; Male; Trimethoprim, Sulfamethoxazole Drug Combination

A case of adverse side effects of co-trimoxazole (Biseptol) was observed, with predominance of neurological changes in the clinical picture. Attention is called to the infrequent occurrence of such side effects of this drug and to the necessity of prompt diagnostic and therapeutic management of such cases.

Topics: Acute Disease; Adult; Bronchitis; Combined Modality Therapy; Disorders of Excessive Somnolence; Drug Hypersensitivity; Headache; Humans; Male; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Administration, Oral; Child, Preschool; Diagnosis, Differential; Drug Hypersensitivity; Female; Fever; Humans; Infant; Male; Trimethoprim, Sulfamethoxazole Drug Combination

This study describes an in vitro method to evaluate a PAF acether release test (PART) from white blood cells after antigenic challenge. PAF acether activity of the supernatant was tested by platelet aggregation. The aggregating power was abolished by using SRI 63-441 (Sandoz), a PAF acether inhibitor. This method was applied to 57 patients with allergic or pseudo-allergic reactions to drugs by using different drug protein conjugates. The results of PART were evaluated in relation to the clinical history (score of imputability) and to other tests (skin tests, lymphocyte transformation tests (LTT), IgE-RAST). A good correlation was found between the release of PAF acether and a high predictability score: sensitivity 75%, specificity 83.8%. PART also correlated with skin tests (75% agreement, n = 60), with LTT (67.7% agreement, n = 74) and in 65.6% of cases with positive penicillin IgE-RAST (n = 32). This method brings a new possibility for the investigation of drug-allergic and pseudo-allergic reactions.

Topics: Antigens; Aspirin; Drug Hypersensitivity; Humans; Immunoglobulin E; Leukocytes; Lidocaine; Lymphocyte Activation; Penicillins; Platelet Activating Factor; Platelet Aggregation; Predictive Value of Tests; Quinolinium Compounds; Radioallergosorbent Test; Sensitivity and Specificity; Skin Tests; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Administration, Intranasal; Aerosols; Bone Marrow Transplantation; Cost-Benefit Analysis; Drug Hypersensitivity; Humans; Pentamidine; Pneumonia, Pneumocystis; Transplantation, Homologous; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (TMP-SMX) is frequently used in human immunodeficiency virus (HIV)-infected patients (HIV+) for treatment or prophylaxis of Pneumocystis carinii pneumonia (PCP). Up to 80% of those patients report adverse reactions to that drug combination. To test the hypothesis that these reactions are immunologically mediated, we quantitated specific IgG and IgE SMX-human serum albumin (HSA) antibodies and immune complexes (IC) in HIV+ patients and in HIV controls. Patients with mild HIV disease had elevated specific SMX-HSA IgG and IC levels compared with those having severe disease or with controls. Conversely, patients with severe HIV disease had statistically elevated levels of specific IgE when compared with patients having milder disease or with controls. There were no differences in either specific antibody or IC levels between patients reporting adverse reactions and those who did not. Results suggest that there are increased levels of SMX-HSA-specific antibodies in some HIV+ patients. The presence of these antibodies appears to be related to severity of disease, rather than clinically significant drug sensitivity.

Topics: Antigen-Antibody Complex; Drug Hypersensitivity; HIV Seropositivity; Humans; Immunoglobulin G; Sulfamethoxazole; Trimethoprim, Sulfamethoxazole Drug Combination

One week after treatment of a urinary infection with co-trimoxazole (twice daily 160 mg trimethoprim and 800 mg sulphamethoxazole) a 21-year-old man suddenly started to vomit, accompanied by watery diarrhoea, abdominal swelling and weight loss of 5 kg. Plain X-ray film of the abdomen while standing showed multiple fluid levels in the small intestine of the upper and lower abdomen. Serum IgE concentration was elevated to 325 U/ml. There was a leukocytosis of 25,800/microliters, with a differential count of 45% eosinophils. Protein-rich ascites contained numerous eosinophils and the mucosa of the terminal ileus and the duodenum was infiltrated with eosinophils, findings which indicated eosinophilic gastroenteritis. All symptoms regressed completely within 10 days of stopping co-trimoxazole and administering prednisolone (50 mg/day). Four years later a similar episode of eosinophilic gastroenteritis developed after the patient had taken trimethoprim with a sulphonamide (once daily 180 mg trimethoprim and 820 mg sulphadiazine). It again quickly responded to short-term administration of glucocorticoids.

Topics: Adult; Drug Hypersensitivity; Eosinophilia; Gastroenteritis; Humans; Male; Prednisolone; Recurrence; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Topics: Acquired Immunodeficiency Syndrome; Drug Eruptions; Drug Hypersensitivity; Humans; Male; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Child, Preschool; Desensitization, Immunologic; Drug Hypersensitivity; HIV Infections; Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

IgE-mediated allergic reactions to drugs may be diagnosed on the basis of anamnestic criteria, clinico-pathological manifestations as well as by the measurement of allergen-specific IgE. The concordance of these diagnostic procedures was investigated in 50 patients with a history of sensitivity to penicillin (12), sulphamethoxazole (9) or both (14), aspirin (2) and pyrazolones (13). All subjects displayed chronic urticaria/angioedema syndrome. Optimal concordance values were observed for penicillin and sulphamethoxazole, while no specific IgE were detected in the ASA-sensitive group. False positive results were noted in pyrazolone-sensitive patients with high total IgE levels. Based on these results, serological methods that detect drug-specific IgE may be carefully used as complementary diagnostic procedure only in those patients in whom an adverse reaction to antibiotics is suspected.

Topics: Antibody Specificity; Aspirin; Drug Hypersensitivity; Humans; Immunoglobulin E; Penicillins; Pyrazoles; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Coccidiosis; Drug Hypersensitivity; Enteritis; Humans; Male; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination

In three of eight patients with the acquired immune deficiency syndrome the Pneumocystis carinii pneumonia treated with intravenous trimethoprim sulfamethoxazole, drug-related reactions occurred 9, 10, and 13 days after therapy. The symptom complex consisted of a maculopapular eruption, fever, eosinophilia, and leukopenia. Oral desensitization with graded doses of trimethoprim sulfamethoxazole was successfully achieved in two of the three patients.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Adult; Anti-Infective Agents; Desensitization, Immunologic; Drug Combinations; Drug Eruptions; Drug Hypersensitivity; Humans; Male; Pneumonia, Pneumocystis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Thirty-four homosexual patients with AIDS were treated for Pneumocystis carinii pneumonia between April 1984 and November 1985. All 31 survivors were treated with oral trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis immediately upon completion of intravenous therapy, despite the prior occurrence of hypersensitivity reactions to intravenous TMP-SMX in 21 of these patients. Only four patients had subsequent reactions to oral TMP-SMX requiring the drug's discontinuation. None of the patients remaining on prophylaxis developed recurrent Pneumocystis pneumonia. Oral TMP-SMX appears effective at preventing recurrent Pneumocystis pneumonia in patients with AIDS. Hypersensitivity reactions during therapy with TMP-SMX may not be a contraindication to continuation of therapy and subsequent oral prophylaxis.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Adult; Anti-Infective Agents; Cohort Studies; Drug Combinations; Drug Eruptions; Drug Hypersensitivity; Fever; Humans; Injections, Intravenous; Male; Pneumonia, Pneumocystis; Recurrence; Sulfamethoxazole; Tablets; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Drug Hypersensitivity; Female; Humans; Hypersensitivity, Delayed; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination

We report the case of a 26-yr-old patient with fulminant liver failure and acute hemorrhagic pancreatitis secondary to the use of trimethoprim-sulfamethoxazole (Bactrim DS). Our patient presented with skin rash and decreased C3 and C4 levels, which we believed was due to a hypersensitivity reaction secondary to the sulfonamide component (sulfamethoxazole). To our knowledge, this is the first case reported in which sulfamethoxazole-trimethoprim has been implicated as a cause of fulminant liver failure and acute hemorrhagic pancreatitis simultaneously, and emphasizes the need of discontinuing this medication as soon as there is evidence of liver and pancreatic dysfunction.

Topics: Adult; Chemical and Drug Induced Liver Injury; Complement C3; Complement C4; Drug Hypersensitivity; Erythema; Hemorrhage; Humans; Male; Pancreatitis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Adult; Drug Combinations; Drug Hypersensitivity; Humans; Male; Pneumonia, Pneumocystis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Adult; Combined Modality Therapy; Desensitization, Immunologic; Drug Combinations; Drug Hypersensitivity; Humans; Male; Opportunistic Infections; Pneumonia, Pneumocystis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

A patient with acquired immunodeficiency syndrome (AIDS) developed rash, fever, neutropenia, and elevated liver function tests during an initial course of trimethoprim-sulfamethoxazole (TMP-SMX) therapy. Upon reexposure to the drug, the patient experienced a severe anaphylactoid reaction associated with pulmonary edema and rhabdomyolysis. Reactions associated with TMP-SMX rechallenge in this patient population have been previously reported but have not been associated with this degree of severity. TMP-SMX therapy should be instituted with extreme caution in patients with AIDS who have demonstrated a prior hypersensitivity reaction to the drug.

Topics: Acquired Immunodeficiency Syndrome; Adult; Dermatitis, Exfoliative; Drug Combinations; Drug Hypersensitivity; Fever; Humans; Hypersensitivity, Delayed; Male; Pneumonia, Pneumocystis; Pulmonary Edema; Rhabdomyolysis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Adult; Anti-Infective Agents; Drug Combinations; Drug Hypersensitivity; Hemophilia A; Humans; Male; Pneumonia, Pneumocystis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

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

Topics: Child; Drug Combinations; Drug Hypersensitivity; Humans; Male; Malpractice; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (co-trimoxazole) is used extensively for treatment of pulmonary and urinary tract infections. Side effects may affect skin, blood, bone marrow, kidney and the liver. Although a number of sulfonamides have been reported to have produced hepatic lesions, hepatitis following therapy with trimethoprim-sulfamethoxazole is a rather rare event. While trimethoprim has not yet been reported as a cause of hepatic disorders, sulfamethoxazole has occasionally been described as inducing hepatic injury. In some cases, these reactions are accompanied by symptoms indicative for allergic reactions such as fever, rash and eosinophilia. Seven well documented cases are analyzed and discussed with respect to the nature of side effects caused by co-trimoxazole.

Topics: Adult; Aged; Anti-Infective Agents; Chemical and Drug Induced Liver Injury; Drug Combinations; Drug Hypersensitivity; Female; Humans; Male; Middle Aged; 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

Topics: Acquired Immunodeficiency Syndrome; Drug Combinations; Drug Hypersensitivity; Humans; Pyrimethamine; Sulfadoxine; Sulfamethoxazole; Sulfanilamides; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Adult; Diphenhydramine; Drug Combinations; Drug Hypersensitivity; Drug Therapy, Combination; Humans; Male; Pneumonia, Pneumocystis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Chemical and Drug Induced Liver Injury; Cholestasis, Intrahepatic; Drug Combinations; Drug Hypersensitivity; Female; Humans; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Topics: Adult; Drug Combinations; Drug Hypersensitivity; Humans; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

We reviewed the charts of 38 patients with the acquired immunodeficiency syndrome who were treated for Pneumocystis carinii pneumonia. Only 5 of 37 patients started on trimethoprim-sulfamethoxazole were able to complete treatment; in 29 patients drug toxicity occurred and in 19 treatment was changed due to adverse reactions that included rash, fever, neutropenia, thrombocytopenia, and transaminase elevation. Pentamidine was given to 30 patients (1 as initial treatment); toxicity occurred in 13 but only 4 required a change in drug. Adverse reactions from pentamidine included fever, rash, neutropenia, transaminase elevation, azotemia, and hypoglycemia. Patients received trimethoprim-sulfamethoxazole a median of 9.5 days, and pentamidine, a median of 12.5 days. Toxicity from trimethoprim-sulfamethoxazole appeared earlier than toxicity associated with pentamidine (7.5 versus 9.5 days of treatment). In patients with the acquired immunodeficiency syndrome, trimethoprim-sulfamethoxazole has a higher incidence of adverse reactions than pentamidine (p less than 0.005).

Topics: Acquired Immunodeficiency Syndrome; Adult; Drug Combinations; Drug Eruptions; Drug Hypersensitivity; Fever; Humans; Leukopenia; Male; Middle Aged; Pentamidine; Pneumonia, Pneumocystis; Retrospective Studies; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Clinical features of 49 episodes of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome were compared with those of 39 episodes in patients with other immunosuppressive diseases. At presentation patients with the syndrome were found to have a longer median duration of symptoms (28 days versus 5 days, p = 0.0001), lower mean respiratory rate (23.4 versus 30, p = 0.005), and higher median room air arterial oxygen tension (69 mm Hg versus 52 mm Hg, p = 0.0002). The survival rate from 1979 to 1983 was similar for the two groups (57% and 50% respectively). Patients with the syndrome had a higher incidence of adverse reactions to trimethoprim-sulfamethoxazole (22 of 34 versus 2 of 17, p = 0.0007). Survivors with the syndrome at initial presentation had a significantly lower respiratory rate, and higher room air arterial oxygen tension, lymphocyte count, and serum albumin level compared to nonsurvivors. Pneumocystis carinii pneumonia presents as a more insidious disease process in patients with the syndrome, and drug therapy in these patients is complicated by frequent adverse reactions.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Aged; Child; Drug Combinations; Drug Eruptions; Drug Hypersensitivity; Female; Humans; Immunologic Deficiency Syndromes; Leukocyte Count; Leukopenia; Male; Middle Aged; Pentamidine; Pneumonia, Pneumocystis; Prognosis; Respiration; Retrospective Studies; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Adult; Drug Combinations; Drug Hypersensitivity; Humans; Male; Pneumonia, Pneumocystis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Drug Combinations; Drug Hypersensitivity; Female; Humans; Meningitis; Meningitis, Aseptic; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Conjunctival Diseases; Drug Combinations; Drug Hypersensitivity; Humans; Male; Middle Aged; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination