A systematic review of randomised clinical trials for oral antibiotic treatment of acute pyelonephritis.

There is increasing resistance to the oral antibiotics currently recommended for the treatment of pyelonephritis, and increased healthcare costs are associated with the reliance on alternative intravenous agents. We, therefore, performed a systematic review of randomised controlled trials to determine the clinical efficacy and safety of oral antibiotics for the treatment of pyelonephritis in adults. A search of four major medical databases (MEDLINE, Embase+ Embase classic, CENTRAL and Cochrane Database for Systematic Reviews) in addition to manual reference searching of relevant reviews was conducted. Clinical cure and adverse event rates were reported, and trial quality and bias were assessed. A total of 277 studies were reviewed; five studies matched all eligibility criteria and were included. Antibiotics included were cefaclor, ciprofloxacin, gatifloxacin, levofloxacin, lomefloxacin, loracarbef, norfloxacin, rufloxacin and trimethoprim-sulfamethoxazole. In included studies, the clinical success of the outpatient treatment of pyelonephritis by cefaclor, ciprofloxacin and norfloxacin at 4 to 6 weeks was comparable at between 83 to 95%. Relatively high rates of adverse events were noted in a trial of ciprofloxacin (24%) and trimethoprim-sulfamethoxazole (33%). Significant heterogeneity between all aspects of the trial designs was identified, with all studies having a potential for bias. This review demonstrates a need for high-quality clinical trials into the oral antibiotic treatment of pyelonephritis, with more consistent designs and reporting of outcomes. There are data to support further research into oral norfloxacin and cefaclor for the outpatient treatment of pyelonephritis in adults.

Old antibiotics for multidrug-resistant pathogens: from in vitro activity to clinical outcomes.

Antimicrobial resistance is a major and emerging threat worldwide. New antimicrobials have been unable to meet the resistance challenge, and treatment options are limited for a growing number of resistant pathogens. More and more clinicians are relying on older antimicrobials for the treatment of multidrug-resistant (MDR) bacteria. Some older antimicrobials have maintained excellent in vitro activity against highly resistant pathogens. In some instances, use of older agents is limited by unfavourable pharmacokinetic/pharmacodynamic characteristics and/or toxicities. In general, clinical data pertaining to the use of older agents for the treatment of MDR pathogens are scarce. Research efforts should be focused on the evaluation of older agents for the treatment of MDR pathogens as well as evaluating how these agents perform in complex patient populations with various and multiple co-morbid conditions.

Drug-induced Hypersensitivity Syndrome Accompanied by Pulmonary Lesions Exhibiting Centrilobular Nodular Shadows.

A 51-year-old woman diagnosed with Crohn's disease developed drug-induced hypersensitivity syndrome (DIHS) 12 and six weeks after starting the oral intake of mesalazine and trimethoprim/sulfamethoxazole, respectively. Chest CT showed centrilobular nodular shadows and a transbronchial lung biopsy (TBLB) revealed infiltration of inflammatory cells predominantly in the small pulmonary artery walls and bronchiolar walls. Regarding pulmonary lesions of DIHS, infiltrative shadows have sometimes been reported, whereas nodular shadows have rarely been documented. This is a valuable case report for considering the mechanism underlying the development of pulmonary lesions in case of DIHS.

Retinal hemorrhages and intermediate uveitis in a patient with drug reaction with eosinophilia and systemic symptoms syndrome: a case report.

PURPOSE: To report a case of drug reaction (or rash) with eosinophilia and systemic symptoms syndrome in association with intraretinal hemorrhages and intermediate uveitis. METHODS: Single case report. RESULTS: A 22-year-old Hispanic woman developed a facial rash and blurry vision after the use of oral trimethoprim-sulfamethoxazole for a urinary tract infection. Fundus examination revealed bilateral +2 vitritis and intraretinal hemorrhages in all four quadrants. An oral mucosal biopsy revealed V-shaped coagulative necrosis, intraepithelial and superficial acute and lymphoplasmacytic inflammation, consistent with drug hypersensitivity reaction. CONCLUSION: Drug reaction (or rash) with eosinophilia and systemic symptoms syndrome can present as cutaneous rash, mucosal lesions, eosinophilia, intermediate uveitis, and intraretinal hemorrhages. In such cases, vitreoretinal manifestations may be considered as diagnostic criteria instead visceral involvement.

Short-acting sulfonamides near term and neonatal jaundice.

OBJECTIVE: To investigate the association between maternal use of sulfamethizole near term and the risk of neonatal jaundice. METHODS: We conducted a nationwide population-based retrospective cohort study using Danish registers. All Danish women giving birth between 1995 and 2007 were included from the Danish Fertility Database. Women redeeming a prescription for sulfamethizole up to 4 weeks before giving birth were identified from the National Prescription Register. The primary outcome was the number of neonates diagnosed with jaundice between birth and age 28 days identified in the National Hospital Register. Risk of neonatal jaundice was calculated as odds ratios (ORs) with linear logistic regression with and without adjustment for confounders. RESULTS: We identified 841,900 births. Of 1,823 (0.2%) neonates exposed to sulfamethizole up to 4 weeks before birth, 197 (10.8%) developed neonatal jaundice. The OR of developing neonatal jaundice after exposure to sulfamethizole was 2.35 (95% confidence interval [CI] 2.02-2.72). Adjustment for maternal age, education, household income, parity, and period of conception left OR unchanged at 2.29 (95% CI 1.97-2.67). After further adjustment for gestational age, the risk associated with sulfamethizole was rendered insignificant (OR 1.03, 95% CI 0.86-1.22). Narrowing exposure time to the last week before birth did not change the estimates. Broken into gestational age groups, the rate of neonates with jaundice after exposure was similar to the rate of unexposed neonates with jaundice. CONCLUSIONS: We found no association between redeeming a prescription of sulfamethizole near term and increased risk of neonatal jaundice. We showed that the presumed association is the result of preterm birth, which can be caused by maternal urinary tract infection. LEVEL OF EVIDENCE: II.

Cyclosporine for SJS/TEN: a case series and review of the literature.

Clear guidelines for the treatment of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are lacking due to its infrequency and the absence of large controlled studies. Systemic corticosteroids and intravenous immunoglobulin (IVIG) have received considerable attention, though reports of the use of these agents have demonstrated mixed success rates in improving morbidity and mortality from SJS/TEN. We present a case series of 4 patients with SJS/TEN who rapidly responded to treatment with cyclosporin A (CsA). We discuss the proposed mechanism of action and the rationale for the use of cyclosporin based on the currently understood pathophysiologic mechanism of TEN.

Trimethoprim-sulfamethoxazole-induced hyperkalemia in patients receiving inhibitors of the renin-angiotensin system: a population-based study.

BACKGROUND: Trimethoprim therapy can cause hyperkalemia and is often coprescribed with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs). The objective of this study was to characterize the risk of hyperkalemia-associated hospitalization in elderly patients who were being treated with trimethoprim-sulfamethoxazole along with either an ACEI or an ARB. METHODS: We conducted a population-based, nested case-control study of a cohort of elderly patients 66 years or older who were residents of Ontario, Canada, and who were receiving continuous therapy with either an ACEI or an ARB. Case patients were those with a hyperkalemia-associated hospitalization within 14 days of receiving a prescription for trimethoprim-sulfamethoxazole, amoxicillin, ciprofloxacin, norfloxacin, or nitrofurantoin. For each case, we identified up to 4 control patients from the same cohort matched for age, sex, and presence or absence of chronic renal disease and diabetes. Odds ratios were determined for the association between hyperkalemia-associated hospitalization and previous antibiotic use. RESULTS: During the 14-year study period, we identified 4148 admissions involving hyperkalemia, 371 of which occurred within 14 days of antibiotic exposure. Compared with amoxicillin, the use of trimethoprim-sulfamethoxazole was associated with a nearly 7-fold increased risk of hyperkalemia-associated hospitalization (adjusted odds ratio, 6.7; 95% confidence interval, 4.5-10.0). No such risk was found with the use of comparator antibiotics. CONCLUSIONS: Among older patients treated with ACEIs or ARBs, the use of trimethoprim-sulfamethoxazole is associated with a major increase in the risk of hyperkalemia-associated hospitalization relative to other antibiotics. Alternate antibiotic therapy should be considered in these patients when clinically appropriate.

Electrocardiographic changes after shoulder arthroplasty.

Hyperkalemia is a commonly encountered electrolyte abnormality in the hospitalized patient population, and can be fatal if not recognized and treated in a timely matter. Although most cases of hyperkalemia in the acute care setting occur in the context of renal failure, certain drugs can cause an increase in serum potassium. One such drug is trimethoprim-suflamethoxazole, a broad spectrum antibiotic utilized for a variety of infections. Reported herein, is the case of an elderly patient who developed marked changes noted on the cardiac monitor following shoulder surgery who was found to have severe hyperkalemia secondary to recent administration of trimethoprim-sulfamethoxazole for a urinary tract infection.

Cholestatic hepatitis with severe systemic reactions induced by trimethoprim-sulfamethoxazole.

Trimethoprim-Sulfomethoxazole (TMP-SMX) related hepatotoxicity and associated severe systemic reaction are not frequent and documented only in case reports. We report a case of a 30-year-old man, who underwent a 15-day therapy with TMP-SMX for urinary tract infection and two weeks later developed acute cholestatic hepatitis, fever and a skin rash followed by severe systemic reaction. He was admitted in Intensive Care unit and with supportive therapy and prednisolone administration, he showed subsequent improvement over a period of few days. He had fully recovered months later. All tests for other causes of liver disease were negative and his liver biopsy showed evidence of drug-induced hepatic injury.

Uncomplicated urinary tract infection in women. Current practice and the effect of antibiotic resistance on empiric treatment.

OBJECTIVE: To review treatment recommendations for empiric therapy of uncomplicated urinary tract infection (uUTI) in light of evolving antibiotic resistance and to consider use of guidelines to promote optimal practice. QUALITY OF EVIDENCE: PubMed was searched and additional relevant references were identified by reviewing articles found in the search. Guidelines were identified through discussion with family practitioners. Level of evidence was assessed for recommendations. MAIN MESSAGE: Many women have uUTIs. The treatment approach is usually empiric antimicrobial therapy without obtaining pretherapy cultures. Trimethoprim-sulfamethoxazole is standard first-line empiric treatment. While resistance to this drug is increasing, it remains only about 10% in community-acquired Escherichia coli in Canada. Concerns about increased resistance have contributed to greater use of fluoroquinolones, but widespread empiric use of this class of medications might promote resistance to fluoroquinolones. Hence, fluoroquinolones should not be considered first-line therapy. While guidelines for treatment of uUTIs have been developed, their usefulness is compromised by their conflicting recommendations. CONCLUSION: Trimethoprim-sulfamethoxazole and nitrofurantoin remain first-choice empiric therapy for uUTIs. Development of guidelines relevant to family physicians and community education programs that incorporate local susceptibility patterns are important strategies for promoting optimal practice.

Adverse pregnancy outcome in users of sulfamethizole during pregnancy: a population-based observational study.

OBJECTIVE: To estimate the risk of adverse birth and neonatal outcome, and miscarriage in women who used sulfamethizole during pregnancy. METHODS: The association between use of sulfamethizole and adverse birth and neonatal outcome was investigated in a case-control and a cohort study in Denmark. We used data from the Prescription Database, the Birth Registry and the Hospital Discharge Registry in North Jutland County to study any association between sulfamethizole use and first recorded miscarriage. The cohort analysis included 3484 women who received a prescription for sulfamethizole from 30 days before conception to date of delivery, and 60175 women who did not use a sulphonamide-containing drug during pregnancy or 30 days before conception. The case-control analysis included 3347 women who had a miscarriage, of whom 90 had taken sulfamethizole, and 22599 primiparous controls who had a live birth. RESULTS: Among women who received prescriptions for sulfamethizole, adjusted odds ratios and 95% confidence intervals for adverse birth outcome were: malformation 1.17 (0.95-1.43); low birth weight 0.69 (0.49-0.98); pre-term birth 1.12 (0.97-1.30); stillbirth 1.02 (0.61-1.68); neonatal jaundice 1.14 (0.38-3.46); and for receiving a prescription for sulfamethizole within 1 week before miscarriage 1.66 (0.92-2.99). CONCLUSIONS: We found no increased risk of congenital malformation, stillbirth or pre-term birth, and no association between use of sulfamethizole late in pregnancy and risk of neonatal jaundice. There was an increased risk of miscarriage after exposure to sulfamethizole during the week before miscarriage, but further studies are needed to evaluate whether this increased risk is causal.

Trimethoprim/sulfamethoxazole-induced toxic epidermal necrolysis.

OBJECTIVE: To report a case of toxic epidermal necrolysis (TEN) associated with trimethoprim/sulfamethoxazole (TMP/SMX). CASE SUMMARY: A 34-year-old Asian woman developed a severe, desquamating mucocutaneous reaction (TEN) after six days of taking TMP/SMX to treat a presumed urinary tract infection (UTI). DISCUSSION: TMP/SMX is often recommended as first-line therapy for UTIs, sinusitis, bronchitis, and as prophylaxis and treatment for Pneumocystis carinii pneumonia. TEN is a rare, but severe condition associated with sulfonamide use. This article describes a typical case and offers an opportunity for review of this potentially serious reaction. CONCLUSIONS: Sulfonamides are often implicated in the majority of drug-induced cases of TEN. This case report illustrates the typical presentation of sulfonamide-induced TEN with a prodrome, characteristic rash, mucous membrane lesions, and systemic involvement. Practitioners should be aware of this rare adverse effect and closely observe patients for cutaneous manifestations or complaints. Any suspected drug should be discontinued if clinical evaluation leads to the suspicion of Stevens-Johnson syndrome or TEN.

[Effects of drugs on the liver. A review illustrated with 3 clinical cases]. / Medikamentel leverpåvirkning. En oversigt illustreret med tre kliniske tilfoelde.

Eleven hundred cases of drug induced liver disease have been reported in Denmark from 1978 to 1987, including 52 fatal cases. Approximately 100 new cases have been reported every year since 1987. The definition and classification of drug induced liver disease are presented together with a review of the most common patho-anatomical pictures and pathogenetic mechanisms, followed by a description of symptoms and paraclinical abnormalities for each of the ten most common drugs causing serious liver disease. Individual cases of liver disease caused by paracetamol, sulfamethizole and androgenic steroid hormones are presented. Guidelines to minimize the risk of liver disease when using halothane, disulfiram or methotrexate are mentioned. Finally there are some proposals for diminishing the number of and the severity of drug induced liver disease.

Nocardiosis. A literature review with selected case reports in two dogs.

Two dogs with systemic nocardiosis are presented and the pathobiology, diagnosis, and treatment of nocardial infections are discussed. Both dogs had nonspecific respiratory signs and depression. The diagnosis was made by isolation of the organism only after surgical drainage was established and appropriate tissues were cultured. The response to surgical drainage and antimicrobial therapy was dramatic in both dogs, but one dog experienced a drug reaction to trimethoprim-potentiated sulfonamide. Although systemic nocardial infections traditionally have had a grave prognosis, through early diagnosis, surgical intervention, and the use of newer, safer and synergistically acting antimicrobials, the prognosis has improved. This article reviews current human and veterinary literature regarding the microbiology, pathogenesis, and treatment of nocardiosis and reports on the successful treatment of systemic nocardiosis in two dogs.

Computed tomography of the brain, hepatotoxic drugs and high alcohol consumption in male alcoholic patients and a random sample from the general male population.

Computed tomography (CT) of the brain was performed in a random sample of a total of 195 men and 211 male alcoholic patients admitted for the first time during a period of two years from the same geographically limited area of Greater Stockholm as the sample. The same medical, social and neuroradiological methods were used for examination of the alcoholic inpatients as for the random controls. Laboratory tests were performed, including liver and pancreatic tests. Toxicological screening was performed and the consumption of hepatotoxic drugs was also investigated and the following were the types of drugs used: antiarrhythmics, antiepileptics, antiphlogistics, mixed analgesics, barbiturates, sulphonamides, benzodiazepines, clomethiazole and phenothiazine derivatives, all of which are metabolised by the liver. The group of male alcoholic inpatients and the random sample were then subdivided with respect to alcohol consumption and use of hepatotoxic drugs: Group IA, men from the random sample with low or moderate alcohol consumption and no use of hepatotoxic drugs; IB, men from the random sample with low or moderate alcohol consumption with use of hepatotoxic drugs; IIA, alcoholic inpatients with use of alcohol and no drugs; and IIB, alcoholic inpatients with use of alcohol and drugs. Group IIB was found to have a higher incidence of cortical and subcortical changes than group IA. Group IB had a higher incidence of subcortical changes than group IA, and they differed only in drug use. Groups IIB and IIA only differed in drug use, and IIB had a higher incidence of brain damage except for anterior horn index and wide cerebellar sulci indicating vermian atrophy. Significantly higher serum (S) levels of bilirubin, gamma-glutamyl transpeptidase (GGT), aspartate aminotransferase (ASAT), alanine amino-transferase (ALAT), creatine kinase (CK), lactate dehydrogenase (LD) and amylase were found in IIB. The results indicate that drug use influences the incidence of cortical and subcortical aberrations, except anterior horn index. It is concluded that the groups with alcohol abuse who used hepatotoxic drugs showed a picture of cortical changes (wide transport sulci and clear-cut or high-grade cortical changes) and also of subcortical aberrations, expressed as an increased widening of the third ventricle.