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1.
Rinsho Ketsueki ; 62(1): 42-46, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-33551424

RESUMO

A 75-year-old man was treated with bendamustine-containing chemotherapy for follicular lymphoma. Trimethoprim-sulfamethoxazole (TMP-SMX) for pneumocystis pneumonia (PCP) prophylaxis was discontinued at the last course of the chemotherapy. However, the patient developed PCP 6 months after the last course, and treatment with TMP-SMX (480 mg/day) was initiated. The TMP-SMX dose was reduced after 3 weeks of treatment. However, PCP recurred 6 days after dose reduction. Increasing the TMP-SMX dose to the therapeutic dose improved PCP. The dose was reduced to a maintenance dose after 7 weeks of the therapeutic dose of TMP-SMX treatment, and PCP did not recur thereafter. This case demonstrated that the early recurrence of PCP after appropriate treatment duration in immunocompromised conditions after chemotherapy, including bendamustine, may require prolonged treatment.


Assuntos
Linfoma Folicular , Pneumonia por Pneumocystis , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Idoso , Humanos , Linfoma Folicular/tratamento farmacológico , Masculino , Recidiva Local de Neoplasia , Pneumonia por Pneumocystis/induzido quimicamente , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/tratamento farmacológico
2.
Medicine (Baltimore) ; 99(33): e20746, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32871970

RESUMO

RATIONALE: Hyponatremia occurs frequently in the hospital setting and may be attributable to a host of etiologies. Drugs are frequently implicated. Trimethoprim-sulfamethoxazole (TMP/SMX) represents a well-recognized pharmacologic precipitant of drug-induced hyponatremia, with several reports extant in the retrievable literature. Nephrologists thus debate the mechanisms giving rise to TMP/SMX-induced hyponatremia and the precise mechanism by which treatment with TMP/SMX generates reductions of serum sodium concentration remain controversial. The agent has a well-known effect of antagonizing the effects of aldosterone upon the distal nephron. Renal salt wasting and the syndrome of inappropriate antidiuretic hormone secretion represent implicated mechanistic intermediaries in TMP/SMX-induced hyponatremia. PATIENT CONCERNS: The patient endorsed no explicit concerns. DIAGNOSES: We describe the case of an 83-year-old female clinically diagnosed with pneumonia found to have an initial serum sodium in the range of 130 to 134 mEq/L consistent with mild hyponatremia upon admission. Sputum cultures grew Achromobacter xylosoxidans susceptible to TMP/SMX. The patient's serum sodium concentration precipitously decline following institution of treatment with TMP/SMX to 112 to 114 mEq/L during the course of 5 days. INTERVENTIONS: Severe hyponatremia proved recalcitrant to initial therapy with supplemental salt tabs and standard doses of the vasopressin receptor antagonist tolvaptan. OUTCOMES: Escalating doses of tolvaptan increased the patient's sodium to 120 to 124 mEq/L. The patient was transferred to another hospital for further management. During her stay, the patient did not exhibit frank or obvious clinical features consistent with hyponatremia nor readily appreciable evidence of volume depletion. LESSONS: TMP/SMX represents a frequent, though underreported cause of hyponatremia in the hospital setting several authors believe natriuresis may represent the most common mechanism underlying TMP/SMX-induced hyponatremia. Evidence implicating natriuresis to be mechanistic in TMP/SMX-induced hyponatremia include clinically appreciable hypovolemia and resolution of hyponatremia with oral or intravenous salt repletion. Salt repletion failed to monotherapeutically enhance our patient's hyponatremiadisfavoring renal salt wasting as originately mechanistic. Contemporaneous refractoriness of serum sodium to fluid restriction nor standard doses of tolvaptan confounded our initial attempts to mechanistically attribute the patient's hyponatremia to a specific cause. Clinical euvolemia and rapid response of hyponatremia to exceptionally high doses of tolvaptan strongly favors syndrome of inappropriate antidiuretic hormone to represent the chief mechanism by which TMP/SMX exacerbates hyponatremia.


Assuntos
Achromobacter denitrificans , Antibacterianos/efeitos adversos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Hiponatremia/induzido quimicamente , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Diagnóstico Diferencial , Feminino , Infecções por Bactérias Gram-Negativas/sangue , Infecções por Bactérias Gram-Negativas/complicações , Humanos , Hiponatremia/complicações , Hiponatremia/fisiopatologia , Hiponatremia/terapia , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
3.
Am J Case Rep ; 21: e926464, 2020 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-32799217

RESUMO

BACKGROUND Although coronavirus disease 2019 (COVID-19) manifests primarily as a lung infection, its involvement in acute kidney injury (AKI) is gaining recognition and is associated with increased morbidity and mortality. Concurrent infection, which may require administration of a potentially nephrotoxic agent, can worsen AKI and lead to poor outcomes. Stenotrophomonas maltophilia is a multidrug-resistant gram-negative bacillus associated with nosocomial infections, especially in severely immunocompromised and debilitated patients. Trimethoprim/sulfamethoxazole combination (TMP/SMX) is considered the treatment of choice but can itself lead to AKI, posing a significant challenge in the management of patients with concomitant COVID-19 and S. maltophilia pneumonia. CASE REPORT A 64-year-old male with end-stage renal disease and post renal transplant presented with severe respiratory symptoms of COVID-19 and was intubated upon admission. His renal functions were normal at the time of admission. The patient subsequently developed superimposed bacterial pneumonia with S. maltophilia requiring administration of TMP/SMX. However, TMP/SMX led to the development of AKI, which continued to worsen despite appropriate management including hemodialysis. This coincided with and most likely resulted in the patient's clinical deterioration and ultimate death. CONCLUSIONS The etiology of kidney disease involvement in patients with COVID-19 is still evolving and appears to be multifactorial. The condition can significantly worsen especially when nephrotoxic agents are given, probably due to a cumulative or synergistic effect. Great caution should be taken when administering nephrotoxic agents in the setting of COVID-19 as it can lead to adverse patient outcomes.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Infecções por Coronavirus/complicações , Infecções por Bactérias Gram-Negativas/complicações , Pneumonia Bacteriana/microbiologia , Pneumonia Viral/complicações , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Betacoronavirus , Deterioração Clínica , Coinfecção , Infecções por Coronavirus/tratamento farmacológico , Evolução Fatal , Humanos , Hospedeiro Imunocomprometido , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Stenotrophomonas maltophilia , Transplantados , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem
4.
J Urol ; 204(6): 1320-1325, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32614253

RESUMO

PURPOSE: We evaluated the effect of long-term low dose antibiotic prophylaxis on children's gut microbiota. MATERIALS AND METHODS: We conducted 16S ribosomal RNA gene sequencing using stool samples from 35 patients younger than 3 years old (median age 5.2 months; male-to-female ratio 17:18) who underwent antibiotic treatment during the acute phase of febrile urinary tract infection. Samples were collected at 5 time points, ie before, during and at 1 to 2, 3 to 4, and 5 to 6 months after febrile urinary tract infection onset and antibiotic treatment. Continuous antibiotic prophylaxis using trimethoprim-sulfamethoxazole was initiated in 23 patients with grade III or higher vesicoureteral reflux and was not administered in 12 patients without reflux. RESULTS: Within 2 weeks after initiation of treatment for febrile urinary tract infection almost all enteric bacteria belonged to the order Lactobacillales, and gut microbiota diversity decreased compared to the pretreatment level (average Shannon index 2.9 before treatment, 1.4 during treatment). The diversity recovered within 1 to 2 months after febrile urinary tract infection onset in both groups. Diversity was maintained during the study period in both groups (p=0.43). A smaller proportion of gut microbiota component belonged to the order Enterobacteriales (p=0.002) in the antibiotic prophylaxis group. CONCLUSIONS: Our results revealed that patients receiving continuous antibiotic prophylaxis had normal gut microbiota diversity, indicating that the effect of trimethoprim-sulfamethoxazole on gut microbiota was insignificant. Furthermore, prophylaxis with trimethoprim-sulfamethoxazole might selectively suppress the growth of bacteria belonging to the order Enterobacteriales, such as Escherichia coli and Klebsiella species, which are the main causative bacteria of febrile urinary tract infections.


Assuntos
Antibacterianos/administração & dosagem , Antibioticoprofilaxia/efeitos adversos , Disbiose/diagnóstico , Microbioma Gastrointestinal/efeitos dos fármacos , Infecções Urinárias/tratamento farmacológico , Refluxo Vesicoureteral/tratamento farmacológico , Antibacterianos/efeitos adversos , Antibioticoprofilaxia/métodos , Bactérias/genética , Bactérias/isolamento & purificação , Pré-Escolar , DNA Bacteriano/isolamento & purificação , Relação Dose-Resposta a Droga , Esquema de Medicação , Disbiose/induzido quimicamente , Disbiose/epidemiologia , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/genética , Humanos , Lactente , Falência Renal Crônica/etiologia , Falência Renal Crônica/prevenção & controle , Masculino , RNA Ribossômico 16S/genética , Resultado do Tratamento , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Infecções Urinárias/complicações , Refluxo Vesicoureteral/diagnóstico , Refluxo Vesicoureteral/etiologia
5.
Int J Clin Pharmacol Ther ; 58(9): 511-517, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32567546

RESUMO

A 66-year-old male patient presented with fever, headache, mental status changes, and nuchal rigidity with a lumbar puncture revealing neutropenic pleocytosis, and a presumptive diagnosis of bacterial meningitis was made. A careful history revealed that symptoms started within hours of starting oral trimethoprim-sulfamethoxazole. Additional history uncovered a nearly identical episode 1 year earlier after 1 dose of trimethoprim-sulfamethoxazole. All microbiologic diagnostic testing for meningitis was negative and all antimicrobials were discontinued. The patient had resolution of symptoms by 96 hours after last dose of trimethoprim-sulfamethoxazole and went on to full recovery. Based on history, clinical course, and a score of 7 on the Naranjo scale, he was diagnosed with recurrent trimethoprim-sulfamethoxazole-induced aseptic meningitis (TSIAM). This case illustrates the profound importance of thorough medication history and medication reconciliation.


Assuntos
Meningite Asséptica , Idoso , Anti-Infecciosos/efeitos adversos , Humanos , Masculino , Meningite Asséptica/induzido quimicamente , Meningite Asséptica/diagnóstico , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos
7.
Ann Pharmacother ; 54(9): 852-857, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32106685

RESUMO

Background: Sulfamethoxazole-trimethoprim (SXT) therapy is commonly used in HIV-infected patients and is associated with hyperkalemia and elevated serum creatinine (SCr). Objective: The purpose of this study was to examine the frequency of hyperkalemia and elevated SCr in hospitalized, HIV-infected patients receiving SXT. Methods: This was a retrospective, single-center cohort study. HIV-infected hospitalized patients receiving a minimum of 3 consecutive days of SXT were included. Patients were grouped according to high dose (≥10 mg/kg/d) and low dose (<10 mg/kg/d) trimethoprim. The primary end point was the frequency of hyperkalemia, severe hyperkalemia, and elevated SCr. Secondary end points included an evaluation of concomitant potassium-altering medications and concomitant nephrotoxic drugs. Results: A total of 100 consecutive patients were selected from all possible patients who met inclusion criteria. Overall, 47 patients experienced at least 1 adverse drug event (ADE) of either hyperkalemia or increased SCr, with 20 patients experiencing these ADEs in the low-dose group and 27 patients experiencing these ADEs in the high-dose group (P = 0.229). The ADEs of hyperkalemia or increased SCr occurred after a shorter period (5.5 vs 8.7 days) in the high-dose group (P = 0.049). Overall frequency of elevated SCr was 24% and of elevated serum K was 36%. Hyperkalemia requiring a therapeutic intervention occurred in 12 patients in the high-dose group compared with 2 in the low-dose group (P = 0.009). Conclusion and Relevance: Rates of elevated SCr and hyperkalemia in hospitalized HIV-infected patients receiving SXT are significant. Hyperkalemia requiring intervention is more common in patients receiving high-dose SXT.


Assuntos
Infecções por HIV/tratamento farmacológico , Hiperpotassemia/induzido quimicamente , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Estudos de Coortes , Creatinina/sangue , Relação Dose-Resposta a Droga , Feminino , Infecções por HIV/sangue , Humanos , Hiperpotassemia/sangue , Masculino , Pessoa de Meia-Idade , Pneumocystis carinii/efeitos dos fármacos , Pneumonia por Pneumocystis/microbiologia , Pneumonia por Pneumocystis/prevenção & controle , Potássio/sangue , Estudos Retrospectivos , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
8.
N Z Med J ; 133(1508): 123-126, 2020 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-31945049

RESUMO

Methotrexate monotherapy is a common management strategy in rheumatoid arthritis (RA). Treatment with immunosuppression can lead to opportunistic infections such as Pneumocystis jirovecii pneumonia (PJP). The treatment options for PJP include cotrimoxazole, clindamycin-primaquine and dapsone. Though these drugs are generally well tolerated, they can result in potentially severe adverse effects. Sometimes several undesired events may occur in a single patient, reminding us of Murphy's law. Herein, we report a case which exemplifies this adage. A 50-year-old female developed PJP, while on methotrexate therapy for RA and was treated with cotrimoxazole. The latter resulted in painful peripheral neuropathy, which improved after cotrimoxazole was stopped. Salvage therapy for PJP with primaquine-clindamycin, lead to another serious adverse event, methemoglobinemia. Withdrawing the offending drug resulted in dramatic improvement.


Assuntos
Aplicação da Lei/métodos , Metemoglobinemia/induzido quimicamente , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Pneumonia por Pneumocystis/tratamento farmacológico , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Antimaláricos/efeitos adversos , Antimaláricos/uso terapêutico , Clindamicina/efeitos adversos , Clindamicina/uso terapêutico , Dapsona/efeitos adversos , Dapsona/uso terapêutico , Quimioterapia Combinada/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Pneumonia por Pneumocystis/complicações , Primaquina/efeitos adversos , Primaquina/uso terapêutico , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Suspensão de Tratamento
9.
Clin Pediatr (Phila) ; 59(3): 259-265, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31888378

RESUMO

It is a common practice to monitor blood tests in patients receiving long-term trimethoprim-sulfamethoxazole (TMP-SMZ) prophylaxis for recurrent urinary tract infections. This multicenter, randomized, placebo-controlled trial enrolled 607 children aged 2 to 71 months with vesicoureteral reflux diagnosed after symptomatic urinary tract infection. Study participants received TMP-SMZ (n = 302) or placebo (n = 305) and were followed for 2 years. Serum electrolytes (n ≥ 370), creatinine (n = 310), and complete blood counts (n ≥ 206) were measured at study entry and at the 24-month study conclusion. We found no significant electrolyte, renal, or hematologic abnormalities when comparing the treatment and placebo groups. We observed changes in several laboratory parameters in both treatment and placebo groups as would normally be expected with physiologic maturation. Changes were within the normal range for age. Long-term use of TMP-SMX had no treatment effect on complete blood count, serum electrolytes, or creatinine. Our findings do not support routine monitoring of these laboratory tests in children receiving long-term TMP-SMZ prophylaxis.


Assuntos
Anti-Infecciosos Urinários/efeitos adversos , Biomarcadores/sangue , Monitoramento de Medicamentos/métodos , Prevenção Secundária/métodos , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Infecções Urinárias/prevenção & controle , Refluxo Vesicoureteral/complicações , Anti-Infecciosos Urinários/uso terapêutico , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Estudos Prospectivos , Recidiva , Resultado do Tratamento , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Infecções Urinárias/sangue , Infecções Urinárias/diagnóstico , Infecções Urinárias/etiologia
10.
Int J Antimicrob Agents ; 55(1): 105820, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31622654

RESUMO

Evidence supporting the use of an echinocandin alone as an alternative agent for the treatment of Pneumocystis jirovecii pneumonia (PCP) is limited and controversial. This retrospective cohort study was conducted at National Taiwan University Hospital from 1 July 2015 to 31 December 2017. Using multivariable Cox regression analyses, the outcomes of patients receiving trimethoprim/sulfamethoxazole (TMP-SMZ) or anidulafungin single therapy as an alternative treatment for PCP were investigated. A total of 207 patients with PCP were screened and 170 patients were included in the final analysis, among whom 134 (78.8%) received TMP-SMZ and 36 (21.2%) received anidulafungin as alternative anti-PCP treatment. Overall 60-day mortality was 34.1% (58/170), and 60-day mortality did not differ significantly between the anidulafungin group (38.9%; 14/36) and the TMP-SMZ group (32.8%; 44/134) (P = 0.554). Age ≥60 years [hazard ratio (HR) = 1.840, 95% confidence interval (CI) 1.039-3.259; P = 0.036] and HIV infection (HR = 0.102, 95% CI 0.013-0.771; P = 0.027) independently predicted 60-day mortality. Patients with lower SpO2/FiO2 ratio (HR = 0.994, 95% CI 0.990-0.998; P = 0.005) showed a higher 60-day mortality. In the Kaplan-Meier survival analysis, anidulafungin as alternative anti-PCP treatment was not correlated with higher mortality (P = 0.605). Using TMP-SMZ or anidulafungin as alternative anti-PCP treatment had similar 60-day mortality. These findings suggest that anidulafungin therapy may be an effective and alternative treatment for PCP in patients who cannot tolerate TMP-SMZ.


Assuntos
Anidulafungina/uso terapêutico , Antifúngicos/uso terapêutico , Equinocandinas/uso terapêutico , Pneumocystis carinii/efeitos dos fármacos , Pneumonia por Pneumocystis/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia por Pneumocystis/microbiologia , Estudos Retrospectivos , Taiwan , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Adulto Jovem
11.
Ann Pharmacother ; 54(4): 351-358, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31694388

RESUMO

Background: Intravenous (IV) sulfamethoxazole/trimethoprim (SMX/TMP) has been associated with hyponatremia in adults. Objective: The primary objective was to identify the number of patients with a serum sodium <135 mEq/L. Secondary objectives between the hyponatremic versus nonhyponatremic groups included demographic comparisons, median serum sodium concentrations, SMX/TMP cumulative dose, number of diuretics, and other medications causing hyponatremia. Methods: This was a retrospective study of children <18 years receiving IV SMP/TMX. Comparisons were conducted via Mann-Whitney-Wilcoxon and Mantel-Haenszel χ2 tests with an a priori P value <0.05. Results: Sixty-one patients received 66 total courses; 20 courses (30.3%) were associated with hyponatremia with a decrease in the median nadir serum sodium concentration of 133 and 138 mEq/L in the hyponatremic and nonhyponatremic groups, respectively (P<0.001). The median age (interquartile range) was lower in the hyponatremic versus nonhyponatremic group, but this was not statistically significant: 0.6 (0.1-5.5) versus 3.9 (0.3-11.0) years; P=0.077. There was no significant difference in the median cumulative dose (mg/kg) between groups; P=0.104. In addition, there was a significant difference in the number of children in the hyponatremic versus nonhyponatremic groups receiving diuretics (16 [80.0%] vs 23 [50.0%], P=0.023) and other medications that cause hyponatremia (7 [35.0%] vs 5 [10.9%], P=0.034), respectively. Furosemide was noted to be the medication most associated with hyponatremia. Conclusion and Relevance: Approximately one-third administered IV SMX/TMP developed hyponatremia. Concomitant furosemide administration was one of the most common risk factors. Clinicians should be aware of this potential adverse event when initiating IV SMX/TMP in children.


Assuntos
Antibacterianos/efeitos adversos , Hiponatremia/induzido quimicamente , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Administração Intravenosa , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Feminino , Furosemida/administração & dosagem , Furosemida/efeitos adversos , Furosemida/uso terapêutico , Humanos , Hiponatremia/epidemiologia , Lactente , Masculino , Estudos Retrospectivos , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
12.
Einstein (Sao Paulo) ; 18: eRC5002, 2020.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31778467

RESUMO

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.


Assuntos
Dessensibilização Imunológica/métodos , Erupção por Droga/tratamento farmacológico , Erupção por Droga/etiologia , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Idoso , Hipersensibilidade a Drogas/tratamento farmacológico , Hipersensibilidade a Drogas/etiologia , Humanos , Masculino , Sulfametoxazol/efeitos adversos , Trimetoprima/efeitos adversos
13.
Pediatrics ; 145(1)2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31796504

RESUMO

OBJECTIVES: Antibiotics are among the most common prescriptions in children, and non-ß-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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.


Assuntos
Antibacterianos/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Adolescente , Criança , Pré-Escolar , Hipersensibilidade a Drogas/epidemiologia , Feminino , Hospitais Pediátricos , Humanos , Lactente , Macrolídeos/efeitos adversos , Masculino , Estudos Retrospectivos , Testes Cutâneos , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Vitória/epidemiologia
14.
Ann Transplant ; 24: 625-630, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31806862

RESUMO

BACKGROUND Trimethoprim-sulfamethoxazole (TMP-SMX) is recommended as prophylaxis against Pneumocystis pneumonia (PCP) in renal transplant recipients. The optimal duration of prophylaxis is unknown. Longer duration of prophylaxis may increase the risk of adverse effects. The aim of this retrospective observational cohort study was to assess the impact of increasing duration of TMP-SMX prophylaxis from 3 to 6 months after transplant on drug-resistant urinary tract infection (UTI), hyperkalemia, peripheral blood cytopenias, and incidence of PCP. MATERIAL AND METHODS Patients transplanted over a 4.5-year period before and after a change in protocol from 3- to 6-months TMP-SMX prophylaxis in our unit were grouped according to planned duration of prophylaxis, and results were analyzed on an intention-to-treat basis. Baseline characteristics, laboratory values, and all urine microbiology results in the 6 months after transplant were analyzed. RESULTS The overall UTI incidence rate was higher in the 3-month (3-m) treatment group than the 6-month (6-m) treatment group (0.52 vs. 0.33 UTI per 100 patient days; rate ratio 1.56 [95% CI 1.27-1.95]). However, this was not attributable to TMP-SMX: the incidences were significantly different in months 0-3 but not months 4-6. Twenty-eight multi-resistant UTIs occurred in the 3-m group, but there were none in the 6-m group (p=0.004). There were no significant differences in renal function, serum potassium, or cytopenias during the first 6 months. There were 15 cases of PCP in the 3-m group, 3 cases in the 6-m group, and no cases during prophylaxis. CONCLUSIONS Extending the duration of TMP-SMX prophylaxis was not associated with change in frequency of UTIs or multi-drug-resistant UTIs, nor was it associated with increased adverse events. TMP-SMX is an effective PCP prophylaxis, and these data support recommendations to extend the duration of prophylaxis after transplant.


Assuntos
Antibioticoprofilaxia/métodos , Transplante de Rim , Pneumonia por Pneumocystis/prevenção & controle , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Antibioticoprofilaxia/efeitos adversos , Estudos de Coortes , Esquema de Medicação , Feminino , Doenças Hematológicas/etiologia , Humanos , Hiperpotassemia/etiologia , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Infecções Urinárias/etiologia
15.
J Immunol Res ; 2019: 8105075, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31886310

RESUMO

Background and Objectives: Pneumocystis pneumonia (PCP) is a common opportunistic infection in acquired immune deficiency syndrome (AIDS) patients that continues to result in a high mortality rate. To develop a better treatment strategy and improve PCP prognosis, a cohort study was conducted to evaluate the therapeutic potential of echinocandin treatment for AIDS patients with PCP (AIDS-PCP). Methods: The AIDS-PCP patients were analyzed in our retrospective cohort study that were hospitalized in The First Affiliated Hospital of Zhejiang University during 2013-2018. The antifungal effects of echinocandins were evaluated in two subgroups that were classified by oxygenation as a proxy for the disease state: PaO2/FiO2 > 200 mmHg and PaO2/FiO2 ≤ 200 mmHg. Intergroup comparisons and survival curves were used to evaluate the effectiveness of the two AIDS-PCP treatment regimens. Results: During the follow-up, 182 AIDS-PCP patients were diagnosed and analyzed in the study. After excluding 55 patients with other superinfections and five patients that were treated with HAART, the remaining 122 patients were enrolled in the study. The group treated with echinocandins combined with trimethoprim-sulfamethoxazole (TMP-SMZ) and clindamycin exhibited a lower mortality rate (9.62%, 5/52) than did the group with TMP-SMZ and clindamycin treatment (20%, 14/70). For AIDS-PCP patients in the PaO2/FiO2 > 200 mmHg subgroup, treatment with echinocandins combined with TMP-SMZ and clindamycin significantly reduced their mortality rate (4.44% (2/45) vs. 18.18% (10/55), P = 0.035). Conclusion: The results of this study indicate that treatment with echinocandins in combination with the standard TMP-SMZ and clindamycin regimen can improve the prognosis and reduce the mortality rate in patients with mild to moderate AIDS-PCP disease.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Clindamicina/uso terapêutico , Equinocandinas/uso terapêutico , Pneumonia por Pneumocystis/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Adulto , Antifúngicos/uso terapêutico , Clindamicina/administração & dosagem , Clindamicina/efeitos adversos , Quimioterapia Combinada , Equinocandinas/administração & dosagem , Equinocandinas/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/etiologia , Resultado do Tratamento , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos
16.
BMC Infect Dis ; 19(1): 950, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703645

RESUMO

BACKGROUND: Bacterial infection of the urinary tract is among the common reasons for seeking medical attention in the community. Rapidly increasing antibiotic resistance of uropathogens is resulting in limited treatment options. Therefore, knowledge of the current uropathogens and their antibiotic susceptibility is important for better treatment of urinary tract infection. METHODS: A cross-sectional study design was conducted from February to September thirty, 2017 among students who came to Mekelle University student's clinics with symptomatic urinary tract infection during the study period.. Mid-stream urine specimens were collected from 341individuals with suspected urinary tract infection for bacteriological identification and antimicrobial susceptibility testing. Data on socio-demographic, clinical and risk factors were also collected using a structured questionnaire. RESULTS: Among the 341 study participants, 72(21.1%) showed significant bacteriuria. Escherichia coli (48.6%), Coagulase-negative staphylococci (23%), Staphylococcus aureus (13.5%), and Klebsiella spp. (8.1%) were common bacterial isolates. Resistance to ampicillin (81-100%), amoxicillin/clavulanic acid (77-93.6%), co- trimoxazole (55 72.3%), nalidixic acid (57.4%) and tetracycline (46-55.5%) was seen by most isolates. Multidrug resistance was observed in 73% of the bacterial isolates, and 25.5% of the Gram-negative isolates were extended-spectrum beta-lactamase producers. Being female, a history of urinary tract infection, a history of catheterization and frequent sexual activity were found to be statistically associated with urinary tract infection. CONCLUSION: Urinary tract infection is a problem among university students with a prevalence of 21.1%. All isolates have developed resistance to most of the commonly used antibiotics. Therefore, health education on the transmission and causes of urinary tract infection are recommended for the students.


Assuntos
Bacteriúria/microbiologia , Infecções por Escherichia coli/microbiologia , Escherichia coli/isolamento & purificação , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação , Estudantes , Adolescente , Adulto , Combinação Amoxicilina e Clavulanato de Potássio/efeitos adversos , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Ampicilina/efeitos adversos , Ampicilina/uso terapêutico , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Bacteriúria/tratamento farmacológico , Estudos Transversais , Farmacorresistência Bacteriana Múltipla , Infecções por Escherichia coli/tratamento farmacológico , Etiópia , Feminino , Humanos , Testes de Sensibilidade Microbiana , Prevalência , Fatores de Risco , Infecções Estafilocócicas/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Universidades , Adulto Jovem
18.
BMC Biol ; 17(1): 76, 2019 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533707

RESUMO

BACKGROUND: The selection pressure exercised by antibiotic drugs is an important consideration for the wise stewardship of antimicrobial treatment programs. Treatment decisions are currently based on crude assumptions, and there is an urgent need to develop a more quantitative knowledge base that can enable predictions of the impact of individual antibiotics on the human gut microbiome and resistome. RESULTS: Using shotgun metagenomics, we quantified changes in the gut microbiome in two cohorts of hematological patients receiving prophylactic antibiotics; one cohort was treated with ciprofloxacin in a hospital in Tübingen and the other with cotrimoxazole in a hospital in Cologne. Analyzing this rich longitudinal dataset, we found that gut microbiome diversity was reduced in both treatment cohorts to a similar extent, while effects on the gut resistome differed. We observed a sharp increase in the relative abundance of sulfonamide antibiotic resistance genes (ARGs) by 148.1% per cumulative defined daily dose of cotrimoxazole in the Cologne cohort, but not in the Tübingen cohort treated with ciprofloxacin. Through multivariate modeling, we found that factors such as individual baseline microbiome, resistome, and plasmid diversity; liver/kidney function; and concurrent medication, especially virostatic agents, influence resistome alterations. Strikingly, we observed different effects on the plasmidome in the two treatment groups. There was a substantial increase in the abundance of ARG-carrying plasmids in the cohort treated with cotrimoxazole, but not in the cohort treated with ciprofloxacin, indicating that cotrimoxazole might contribute more efficiently to the spread of resistance. CONCLUSIONS: Our study represents a step forward in developing the capability to predict the effect of individual antimicrobials on the human microbiome and resistome. Our results indicate that to achieve this, integration of the individual baseline microbiome, resistome, and mobilome status as well as additional individual patient factors will be required. Such personalized predictions may in the future increase patient safety and reduce the spread of resistance. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02058888 . Registered February 10 2014.


Assuntos
Antibacterianos/efeitos adversos , Ciprofloxacino/efeitos adversos , Resistência Microbiana a Medicamentos , Microbioma Gastrointestinal/efeitos dos fármacos , Plasmídeos/efeitos dos fármacos , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Antibacterianos/uso terapêutico , Ciprofloxacino/uso terapêutico , Estudos de Coortes , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Resistência Microbiana a Medicamentos/genética , Genes Bacterianos/efeitos dos fármacos , Alemanha , Humanos , Estudos Longitudinais , Metagenômica/métodos , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
19.
J Allergy Clin Immunol Pract ; 7(7): 2116-2123, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31495421

RESUMO

Sulfonamide antimicrobials are commonly reported as causing drug allergy and have been implicated in a variety of hypersensitivity reactions including immediate IgE-mediated reactions, benign T-cell-mediated rashes, and severe cutaneous adverse reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms. Cross-reactivity is unlikely between sulfonamide antimicrobials and sulfonamide non-antimicrobials. In patients who develop reactions to a sulfonamide non-antimicrobial, there is no evidence to suggest that sulfonamide antimicrobials and other sulfonamide non-antimicrobials would cross-react. Although immediate skin testing can be performed in patients with histories of immediate reactions, they are infrequently positive and wane over time. Delayed skin testing including patch tests to sulfonamides is rarely positive. Drug challenges are a useful tool for patients with both immediate and delayed reactions to sulfonamides. The role of sulfamethoxazole desensitization is controversial as rates of hypersensitivity reactions are similar between desensitization and drug challenge.


Assuntos
Anti-Infecciosos/efeitos adversos , Hipersensibilidade a Drogas/etiologia , Sulfonamidas/efeitos adversos , Quimioprevenção , Reações Cruzadas/imunologia , Dessensibilização Imunológica , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/imunologia , Hipersensibilidade a Drogas/terapia , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Síndrome de Hipersensibilidade a Medicamentos/imunologia , Infecções por HIV , Humanos , Hipersensibilidade Tardia/induzido quimicamente , Hipersensibilidade Tardia/imunologia , Hipersensibilidade Imediata/induzido quimicamente , Hipersensibilidade Imediata/imunologia , Pneumonia por Pneumocystis/prevenção & controle , Teste de Radioalergoadsorção , Testes Cutâneos , Síndrome de Stevens-Johnson/etiologia , Síndrome de Stevens-Johnson/imunologia , Sulfametoxazol , Sulfonamidas/imunologia , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos
20.
BMJ Open ; 9(9): e033393, 2019 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-31551394

RESUMO

OBJECTIVES: This study aimed to assess the evolution of body mass index (BMI) of HIV-positive adults on second-line antiretroviral therapy (ART) over time and factors affecting it in north-west Ethiopia. DESIGN: An institution-based retrospective follow-up study was conducted using data extracted from 1016 patient cards from February 2008 to February 2016. SETTING: Eight referral hospitals from Amhara region, Ethiopia were included. PARTICIPANTS: HIV patients who started second-line ART. OUTCOME MEASURES: Change in BMI since starting second-line ART. RESULTS: Five hundred and thirty-eight (52.95%) participants were males and the median age of the participants was 33 years (IQR: 28; 39). The median follow-up time was 18 months (IQR: 5.2; 32.2). The average change of BMI showed linear increase over time. The amount of BMI increment or decrement according to each variable was shown as ß coefficients. Treatment duration (ß=0.013, 95% CI 0.004 to 0.022), isoniazid prophylaxis (ß=0.87, 95% CI 0.32 to 1.42), cotrimoxazole prophylaxis (ß=0.63, 95% CI 0.08 to 1.19), ambulatory functional status (ß=-1.16, 95% CI -1.95 to 1.31), bedridden functional status (ß=-1.83, 95% CI -2.47 to 1.21), WHO stage III (ß=-0.42, 95% CI -0.65 to 0.20), WHO stage IV (ß=-0.62, 95% CI -1.02 to 0.22), CD4 count (ß=0.001, 95% CI 0.0008 to 0.0015), and time interaction of variables like tertiary educational status (ß=0.02, 95% CI 0.01 to 0.04), ambulatory functional status (ß=0.03, 95% CI 0.01 to 0.05) and WHO stages III (ß=0.01, 95% CI 0.007 to 0.02) were found to be significant predictors. CONCLUSION: The BMI of patients has shown linear increment over the treatment time. Factors affecting it have been identified but its effect on cardiovascular disease needs further study.


Assuntos
Fármacos Anti-HIV , Índice de Massa Corporal , Coinfecção/prevenção & controle , Infecções por HIV , Isoniazida , Combinação Trimetoprima e Sulfametoxazol , Ganho de Peso/efeitos dos fármacos , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/efeitos adversos , Terapia Antirretroviral de Alta Atividade/métodos , Contagem de Linfócito CD4/métodos , Coinfecção/epidemiologia , Etiópia/epidemiologia , Feminino , Seguimentos , Infecções por HIV/sangue , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Isoniazida/administração & dosagem , Isoniazida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos
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