Show Research BMJ 2018; 360 doi: https://doi.org/10.1136/bmj.k341 (Published 09 February 2018) Cite this as: BMJ 2018;360:k341
Ladies, if you think you have a urinary tract infection, you are probably right. One study found that women who self-diagnose a UTI are right 84% of the time. You can apply this know-how to partner with your health care provider to pick the right treatment The go-to treatment of a UTI, which is caused by a bacteria, is antibiotics. Your questions about treatment decisions can make a difference, especially since antibiotic recommendations have shifted and not all doctors have changed their practices. Types of antibioticsHealth care providers usually pick from one of three antibiotics for uncomplicated UTIs (UTIs in the lower urinary tract of non-pregnant, premenopausal women).
There are benefits and risks to each drug. While they all provide relief and help cure the infection, potential side effects include diarrhea, nausea and headaches. If you have allergies to any antibiotics, such as sulfonamide "sulfa" drugs, your treatment might be different. Sulfa allergies are often accompanied by a skin rash or fever, so let your doctor know if this occurs as a result of your treatment. If you are given antibiotics, be sure to follow the instructions and finish the full course of medication given to you. This helps prevent reinfection. Antibiotics that shouldn't be a first choice for uncomplicated UTIsOther antibiotics appear to be overused, and some physicians may misuse non-recommended antibiotics as first-line treatments. Ciprofloxacin (Cipro) is used in 35% of uncomplicated UTIs, while levofloxacin is used in 2%. These antibiotics can be important treatments in some cases of more complicated UTIs, but can have dangerous side effects. The U.S. Food and Drug Administration warns that the use of these drugs should be restricted because of their potentially disabling side effects involving tendons, muscles, joints, nerves and the central nervous system. Additionally, in many parts of the country, bacteria commonly causing UTIs are becoming resistant to these antibiotics. New therapies are emergingIn addition to antibiotics, there are some emerging treatment options, including d-mannose, a sugar that can be taken orally to stop the proliferation of bacteria in the bladder. This is a newer drug and has not yet been incorporated into routine clinical practice. Managing painIf you are prescribed antibiotics, the drugs should provide relief within two to three days. Symptoms such as dysuria, or painful urination, can often be relieved in just a few hours. However, UTIs often cause discomfort, in which case there are options for pain management. Phenazopyridine (brand name Pyridium or AZO) can be prescribed or obtained as an over-the-counter option to give immediate relief. This drug does cause urine and other secretions, such as tears, to turn bright orange, which can sometimes stain contact lenses. While effective as pain reliever, this drug does not treat UTIs. What if I don't go to the doctor?What happens when UTIs are left untreated? Contrary to popular belief, your immune system is often able to clear a UTI on its own. Studies have found that 25-42% of women are able to recover from an uncomplicated UTI without antibiotics. But that means a majority of UTIs do not go away on their own. If left untreated, they can lead to continued discomfort and other more serious health issues, such as kidney damage or a severe infection. Therefore, treatment is recommended. "Physicians tailor care plans to each patient, and there is no sole treatment for everyone," says Stanford physician Kim Chiang, MD. During your visit, feel free to ask in-depth questions, particularly if a non-recommended antibiotic is prescribed. This is the fifth post in the series Understanding UTIs. The goal of this seven-part series is to provide easy-to-understand, scientifically grounded information about UTIs. Patients referenced are composites, compiled from actual patient experiences. Data on medications used for UTIs were extracted from the National Disease and Therapeutic Index, a nationally representative physician survey produced by IQVIA. Joanna Langner is a graduate student in Community Health and Prevention Research at Stanford who is interested in health disparities and women's health. She wrote this series with the support of Randall Stafford, MD, PhD, professor of medicine and director of the Program on Prevention Outcomes and Practices, and Kim Chiang, MD, clinical assistant professor of medicine. Photo by Christina Victoria Craft Trimethoprim/sulfamethoxazole, also known as co-trimoxazole and can be abbreviated in the following ways: SXT, TMP-SMX, TMP-SMZ, or TMP-Sulfa. It is an antimicrobial used to treat and prevent many bacterial infections. This drug is very cost affordable and used for many types of illnesses. The FDA-Approved indications include acute infective exacerbation of chronic bronchitis, otitis media in pediatrics only, travelers diarrhea for treatment and prophylaxis, urinary tract infections, shigellosis, pneumocystis jirovecii, pneumonia/pneumocystis carinii pneumonia (PJP/PCP), and toxoplasmosis, both as prophylaxis and treatment. There are also non-FDA-approved indications. This activity outlines the indications, mechanism of action, methods of administration, important adverse effects, contraindications, toxicity, and monitoring, of TMP-SMX, so providers can direct patient therapy where necessary for infections as part of the interprofessional team. Objectives:
Trimethoprim/sulfamethoxazole, also known as co-trimoxazole and can be abbreviated in the following ways: SXT, TMP-SMX, TMP-SMZ, or TMP-sulfa.[1][2] It is an antimicrobial used to treat and prevent many bacterial infections. In 1974, TMP/SMX healthcare professionals began prescribing the medication, and the drug is now on the list of the World Health Organization's (WHO) essential medicines.[3] This drug is very cost affordable and used for many types of illnesses.[4] The FDA-Approved Indications
The Non-FDA Approved Indications
Sulfamethoxazole is a sulfonamide (antimicrobial drug class) that works directly on the synthesis of folate inside microbial organisms, e.g., bacteria. Sulfamethoxazole achieves this directly as a competitor of p-aminobenzoic acid (PABA) during the synthesis of dihydrofolate via inhibition of the enzyme dihydropteroate synthase. Trimethoprim is a direct competitor of the enzyme dihydrofolate reductase, resulting in its inhibition, which halts the production of tetrahydrofolate to its active form of folate. The combination of these two agents is meant to create a synergistic anti-folate effect; tetrahydrofolate is a necessary component for synthesizing purines required for DNA and protein production. When used alone, these drugs only act in a bacteriostatic manner. However, when used in the combination of sulfamethoxazole-trimethoprim, they block two steps in the bacterial biosynthesis of essential nucleic acids and proteins, thus can be bactericidal, e.g., urine.[5] Sulfamethoxazole is hepatically metabolized by the CYP450 system; it is a CYP2C9 inhibitor. Its half-life is 6 to 12 hours, increasing to between 20 and 50 hours in renal failure. Trimethoprim has a half-life of 8 to 10 hours, is minimally metabolized in the liver, and is primarily excreted in the urine, essentially unchanged. Sulfamethoxazole/trimethoprim may be administered orally without regard to meals. However, it is best to take it with at least 8 ounces of water. It also has an intravenous formulation. The choice of oral or intravenously varies both on the type of infection/or type of prophylactic use. It should not be administered intramuscularly. Patients with impaired renal function must have calculated dosing regimens based on renal function, as listed below. Administration of the two drugs is in a 1 to 5 ratio (trimethoprim:sulfamethoxazole) as a tablet formulation; this is so when they enter the body, their concentration throughout the blood/tissues is 1 to 20, which is the peak synergistic desired effect ratio of the two drugs in combination.[6] Bacterial Infections Oral dosage in adults and children weighing 40 kg (88 pounds) or more should have a single tablet of 800 mg of sulfamethoxazole and 160 mg of trimethoprim every 12 hours for 10 to 14 days. Children 2 months and older must have a weight-adjusted dosage. Treatment of Pneumocystis jirovecii Pneumonia/Pneumocystis carinii Pneumonia Adults/children, two months of age and older: The dose is also weight adjusted. Usually 75 to 100 mg per kilogram of body weight for sulfamethoxazole and 15 to 20 mg per kilogram of body weight for trimethoprim each day for 14 to 21 days.[6] Prevention of Pneumocystis jirovecii pneumonia/ pneumocystis carinii pneumonia In adults, 800 mg of sulfamethoxazole and 160 mg of trimethoprim is given once a day. In children two months of age and older, dosages are determined by body size.[6] Traveler's Diarrhea In adults, 800 mg of sulfamethoxazole and 160 mg of trimethoprim every 12 hours for five days. For children two months and older, use and dosage vary. Chronic Bronchitis For acute exacerbations due to strains of Streptococcus pneumoniae or Haemophilus influenzae, one tablet of 800 mg of sulfamethoxazole and 160 mg of trimethoprim every 12 hours for 10 to 14 days.[7] Shigellosis Enteritis caused by Shigella flexneri and Shigella sonnei: 1 tablet 800 mg of sulfamethoxazole and 160 mg of trimethoprim every 12 hours for five days; antimicrobial resistance is an increasing concern in this infection.[8] Urinary Tract Infections Pyelonephritis One tablet 800 mg of sulfamethoxazole and 160 mg of trimethoprim every 12 hours for 14 days Prostatitis One tablet 800 mg of sulfamethoxazole and 160 mg of trimethoprim every 12 hours for 14 days or 2 to 3 months if a chronic infection.[9] Acne Vulgaris (Non-FDA Approved) One tablet 800 mg of sulfamethoxazole and 160 mg of trimethoprim every 12 hours for 18 days Community-Acquired Pneumonia (Non-FDA Approved) One tablet 800 mg of sulfamethoxazole and 160 mg of trimethoprim every 12 hours for 10 to 14 days Renal impairment guidelines are as follows:
Use is not recommended in children younger than two months of age. The primary adverse effects of trimethoprim/sulfamethoxazole include rash, photosensitivity, as well as folate deficiency.[10][11] A list of the more common side effects includes:
More serious reactions can include Stevens-Johnson syndrome, various anemias, agranulocytosis, C. diff.-associated diarrhea, myelosuppression, renal failure/interstitial nephritis, pancreatitis, and hepatotoxicity. Hemolytic anemia can occur with sulfa drugs like sulfamethoxazole in patients with a glucose-6-phosphate-dehydrogenase (G6PD) deficiency. A patient with an unknown sulfa allergy and treated with trimethoprim/sulfamethoxazole may experience anaphylaxis or less serious yet severe symptoms such as hives, itchy eyes, swelling of the mouth and/or throat, and abdominal cramping.[12] Trimethoprim/Sulfamethoxazole Contraindications
Trimethoprim/sulfamethoxazole is an American pregnancy category D medication. Use during early pregnancy has been related to congenital malformations and maternal folic acid deficiency; this may cause neural tube defects (spina bifida), urinary tract defects, oral clefts, and clubbed feet. Use during late pregnancy has been related to preterm labor. The drug also gets excreted in breast milk, and breastfeeding patients should not use trimethoprim/sulfamethoxazole during this time. Administration of trimethoprim/sulfamethoxazole should not occur concomitantly with any of the following:
When initiating therapy with trimethoprim/sulfamethoxazole, some patients may require a baseline blood urea nitrogen and serum creatinine ratio, frequent complete blood counts (CBC), and electrolyte measurements if the patient has renal impairment or if they are taking a drug that has interactions with potassium. Overdosing on trimethoprim/sulfamethoxazole is possible, and potential signs of toxicity include:
If there is suspicion of a patient having trimethoprim/sulfamethazine toxicity, a treatment plan includes the administration of activated charcoal (if ingested), gastric lavage, and supportive intravenous (IV) and oral fluids. More severe treatment measures may consist of hemodialysis and alkalizing the patient's urine.[5] Prescribing clinicians, including nurse practitioners, primary care providers, physician assistants, and internists who prescribe trimethoprim/sulfamethoxazole (TMP-SMX), should be familiar with ints indications and adverse effects. Also, when a patient receives a prescription of trimethoprim/sulfamethoxazole, some patients may need a baseline blood urea nitrogen and serum creatinine ratio, frequent complete blood counts (CBC), and electrolyte measurements if renal impairment is a known issue or if taking a drug that has interactions with potassium. Pharmacists should be consulted to verify coverage in conjunction with an infectious disease specialist, verify dosing, perform medication reconciliation, and report any concerns to the rest of the healthcare team. Nurses will administer the drug inpatient and can also confirm that there are no adverse events resulting from therapy with TMP-SMX, reporting any concerns immediately to the prescriber. In instances of pediatric use or cases of renal impairment, the pharmacist, nurse, and prescriber should coordinate to ensure proper dosing. As with any medication therapy, antimicrobial treatment with TMP-SMX requires an interprofessional team approach, including physicians, specialists, specialty-trained nurses, and pharmacists, all collaborating across disciplines to achieve optimal patient outcomes. [Level 5] Review Questions1. García-Solache M, Rice LB. The Enterococcus: a Model of Adaptability to Its Environment. Clin Microbiol Rev. 2019 Mar 20;32(2) [PMC free article: PMC6431128] [PubMed: 30700430] 2.Huang L, Chen X, Xu H, Sun L, Li C, Guo W, Xiang L, Luo G, Cui Y, Lu B. Clinical features, identification, antimicrobial resistance patterns of Nocardia species in China: 2009-2017. Diagn Microbiol Infect Dis. 2019 Jun;94(2):165-172. [PubMed: 30679058] 3.Krooks J, Weatherall A, Markowitz S. Complete Resolution of Mycobacterium marinum Infection with Clarithromycin and Ethambutol: A Case Report and a Review of the Literature. J Clin Aesthet Dermatol. 2018 Dec;11(12):48-51. [PMC free article: PMC6334835] [PubMed: 30666280] 4.She WH, Chok KSH, Li IWS, Ma KW, Sin SL, Dai WC, Fung JYY, Lo CM. Pneumocystis jirovecii-related spontaneous pneumothorax, pneumomediastinum and subcutaneous emphysema in a liver transplant recipient: a case report. BMC Infect Dis. 2019 Jan 18;19(1):66. [PMC free article: PMC6339407] [PubMed: 30658592] 5.Eyler RF, Shvets K. Clinical Pharmacology of Antibiotics. Clin J Am Soc Nephrol. 2019 Jul 05;14(7):1080-1090. [PMC free article: PMC6625637] [PubMed: 30862698] 6.Weyant RB, Kabbani D, Doucette K, Lau C, Cervera C. Pneumocystis jirovecii: a review with a focus on prevention and treatment. Expert Opin Pharmacother. 2021 Aug;22(12):1579-1592. [PubMed: 33870843] 7.Falcon M, Iberico C, Guerra F, Reyes I, Felix E, Flores M, de Los Ríos J, Diaz ME, Casas A, Sanchez-Gambetta S, Carrasco R. A pilot study of safety of sulfamethoxazole, trimethoprim and guaifenesin in pediatric and adult patients with acute bronchitis. BMC Res Notes. 2019 Mar 04;12(1):119. [PMC free article: PMC6399863] [PubMed: 30832720] 8.Hosseini Nave H, Mansouri S, Sadeghi A, Moradi M. Molecular diagnosis and anti-microbial resistance patterns among Shigella spp. isolated from patients with diarrhea. Gastroenterol Hepatol Bed Bench. 2016 Summer;9(3):205-10. [PMC free article: PMC4947135] [PubMed: 27458513] 9.Wan CD, Zhou JB, Song YP, Zou XJ, Ma YQ. [Pathogens of prostatitis and their drug resistance: an epidemiological survey]. Zhonghua Nan Ke Xue. 2013 Oct;19(10):912-7. [PubMed: 24218946] 10.McGee M, Brienesse S, Chong B, Levendel A, Lai K. Tropheryma whipplei Endocarditis: Case Presentation and Review of the Literature. Open Forum Infect Dis. 2019 Jan;6(1):ofy330. [PMC free article: PMC6329903] [PubMed: 30648125] 11.Hanlon JT, Perera S, Drinka PJ, Crnich CJ, Schweon SJ, Klein-Fedyshin M, Wessel CB, Saracco S, Anderson G, Mulligan M, Nace DA. The IOU Consensus Recommendations for Empirical Therapy of Cystitis in Nursing Home Residents. J Am Geriatr Soc. 2019 Mar;67(3):539-545. [PMC free article: PMC7980083] [PubMed: 30584657] 12.Gallardo-Cartagena JA, Chiappe-Gonzalez AJ, Astocondor-Salazar LM, Salazar-Mesones BN, Narcizo Susanibar JA, Cucho-Espinoza C, Huaroto-Valdivia LM, Ticona-Chávez ER. [Vibrio cholerae NO-O1/NO-O139 bacteremia in a cirrhotic patient. First case report in Peru and literatura review]. Rev Gastroenterol Peru. 2018 Jul-Sep;38(3):301-305. [PubMed: 30540737] |
A client is prescribed trimethoprim-sulfamethoxazole for treatment of a urinary tract infection
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