Antibacterials By Drug Class PDF

22 | INFECTIOUS DISEASES I BACKGROUND & ANTIBACTERIALS BY DRUG CLA 55 MONOBACTAM AZTREONAM Aztreonam has a mechanism of action similar to beta - lactams; it inhibits bacterial cell wall synthesis by binding to penicillin binding proteins (PBPs) , which prevents the final step of peptidoglycan synt...

22 | INFECTIOUS DISEASES I BACKGROUND & ANTIBACTERIALS BY DRUG CLA 55 MONOBACTAM AZTREONAM Aztreonam has a mechanism of action similar to beta - lactams; it inhibits bacterial cell wall synthesis by binding to penicillin binding proteins (PBPs) , which prevents the final step of peptidoglycan synthesis in bacterial cell walls. The monobactam structure makes cross- reactivity with a beta -lactam allergy unlikely. Aztreonam is primarily used when a beta-lactam allergy is present. Aztreonam covers many Gram - negative organisms, including Pseudomonas . It has no Gram - positive or anaerobic activity. DRUG DOSING SAFETY/ SIDE EFFECTS / MONITORING Aztreonam ( Azactam ) IV: 500- 2.000 mg Q6-12H Injection CrCI < 30 mL/min: dose adjustment required SIDE EFFECTS Similar to penicillins, including rash, N / V/ D, T LFTs Cayston - inhaled, for cystic fibrosis NOTES Can be used with a penicillin allergy See lab interactions , storage requirements and renal dosage information near the end of this chapter. SPECTRUM OF ACTIVITY SUMMARY The chart below provides a visual representation of the spectrum of activity for beta -lactams and aztreonam. It can be used to identify common coverage, including which drugs have unique coverage ( e.g., drugs active against Pseudomonas or MRSA ) , or where coverage is lacking (e.g., drugs that do not cover Enterococcus ). i ! i Q* l/> 2 Scc 2 o E 3 3 2 3 a w> ui o. § s E 8 3 * ~a £ E >& £ £3 M M s 2 st * a i /i UJ - Z . c UJ a UJ UJ C 5 I I E C T3 3 £ Penicillin 1- 1 Z II £2~ e « B SSI !s a 2 2 Penicillin Amoxicillin Amoxicillin Oxacillin Nafcillin Amoxicillin /Clavulanate Ampicillin /Sulbactam Amoxicillin /Clavulanate Ampicillin/Sulbactam Piperacillin /Tazobactam Cefazolin Cephalexin Cefuroxime Cefotetan Cefoxitin Cefotaxime Ceftriaxone Cefazolin Cefazolin Cephalexin Cephalexin Cefuroxime Cefotetan Cefoxitin Cefotetan Cefoxitin Cefotaxime Ceftriaxone Cefotaxime Ceftriaxone Ceftazidime Aztreonam Cefepime Ceftaroline Cefepime Ceftaroline Ceftazidime/Avibactam Ceftolozane/Tazobactam Ceftaroline Ceftazidime/ Avibactam* Ceftolozane/Tazobactam* Imipenem /Cilastatin* * Meropenem* * Doripenem** Ertapenem ’ Must be given with metronidazole for adequate anaerobic coverage *’ E. faecalis only * *‘ No Acinetobocter coverage ;4 Ertapenem* ** Ertapenem * E c o 2? o 3 a £ < RxPrep Course Book | RxPrep C 2019, RxPrep © 2020 ' AMINOGLYCOSIDES AMINOGLYCOSIDES: GOOD NEWS, BAD NEWS Aminoglycosides bind to the ribosome, which interferes with bacterial protein synthesis and results in a defective bacterial cell membrane. They primarily cover Gram - negative bacteria (including Pseudomonas ); gentamicin and streptomycin are used for synergy, in combination with a beta - lactam or vancomycin, when treating Gram - positive infections ( e.g., enterococcal endocarditis ). Streptomycin and amikacin are used as second - line treatment for Mycobacterial infections. Plazomicin, a newer drug in the class, is only indicated for complicated UT1 and pyelonephritis when there are no alternative treatment options. There are two dosing strategies for aminoglycosides; traditional dosing uses lower doses more frequently ( e.g., Q8H if renal function is normal ) . Extended interval dosing uses higher doses ( to attain higher peaks ) less frequently (e.g., once daily if renal function is normal ) . With extended interval dosing there is less accumulation of drug. This dosing strategy has been shown to decrease nephrotoxicity and decrease cost, but it is not clinically superior to traditional dosing. See Study Tip Gal for more on aminoglycosides. GOOD NEWS Aminoglycosides kill Gram * negatives fast, are synergistic with beta - lactams for some organisms, and have low resistance and drug cost. Aminoglycosides demonstrate concentrationdependent activity and have a post -antibiotic effect: the bacterial killing continues after the serum level drops below the MIC. BAD NEWS They have notable toxicities: renal damage and ototoxicity ( hearing loss / tinnitus / balance problems) and require monitoring. SMART IDEA Take advantage of the concentration- dependent kinetics - give larger doses less frequently - this gives the kidneys time to recover between doses. * * DRUG DOSING SAFETY/ SIDE EFFECTS / MONITORING Gentamicin IV, IM, ophthalmic, topical If underweight (< ideal body weight): use total body weight for dosing BOXED WARNINGS Nephrotoxicity, ototoxicity, (hearing loss, vertigo, ataxia); avoid use with other neurotoxic /nephrotoxic drugs; neuromuscular blockade and respiratory paralysis; fetal harm if given in pregnancy Tobramycin IV, IM, ophthalmic, inhaled Tobramycin inhalation for CF (TOBI TOBI Podhaler, Bethkis , Kitabis Pak ) . Amikacin IV, IM If not obese or underweight: ideal body weight or total body weight can be used for dosing (follow the hospital protocol) If obese, use adjusted body weight for dosing (see Notes) Traditional IV Dosing Gentamicin and tobramycin: 1- 2.5 mg/ kg/dose; lower doses are used for Gram -positive infections; higher doses are used for Gram - negative infections - Amikacin: 5 7.5 mg/kg/dose Q8H Renal Dose Adjustments (Traditional Dosing) CrCI 60 mL/min: Q8H CrCI 40- 60 mL/min: Q12H CrCI 20-40 mL/min: Q24H CrCI < 20 mL/min: lx dose, then dose per levels Streptomycin IM Extended Interval IV Dosing (Gentamicin / Tobramycin) Gentamicin and tobramycin: 4-7 mg/ kg/ dose (commonly 7 mg/kg) Frequency (dosing interval) is determined by a nomogram (see the example on the following page) Plazomicin ( Zemdri ) IV ( for complicated UTI; use only when there are no alternative treatment options) Contraindications: pregnancy, ascites, burns, cystic fibrosis, CrCI < 30 mL/min (including end- stage renal disease on dialysis) or when using for synergy in endocarditis Other Dosing Plazomicin 15 mg/kg IV Q24H (dose adjustments required if CrCI < 60 mL/min) WARNINGS Use caution in patients with impaired renal function, in the elderly, and those taking other nephrotoxic drugs (amphotericin B, cisplatin, polymyxins, cyclosporine, loop diuretics, NSAIDs, radiocontrast dye, tacrolimus and vancomycin) SIDE EFFECTS Nephrotoxicity (acute tubular necrosis), hearing loss (early toxicity associated with high-pitched sounds), vestibular toxicity (resulting in balance deficits) MONITORING Drug levels, renal function, urine output, hearing tests Traditional dosing: draw a trough level right before (or 30 minutes before) the 4th dose; draw a peak level 30 minutes after the end of the 30- minute drug infusion for the 4th dose (see the table on the following page for target peaks and troughs) Extended interval dosing: draw a random level per the timing on the nomogram (see the example on the following page) Plazomicin: measure trough concentration 30 minutes before the 2nd dose; goal trough < 3 mcg/mL NOTES Amikacin has the broadest spectrum of activity The clinical definition of obesity varies; for exam purposes, obesity will be obvious, and may be stated in the question, indicating that adjusted body weight should be used for weight-based dosing (see the Calculations IV chapter for more information on weight- based dosing) See lab interactions , storage requirements and renal dosage information near the end of this chapter. 3! 22 | INFECTIOUS DISEASES I ; BACKGROUND & ANTIBACTERIALS BY DRUG CLASS TRADITIONAL DOSING: TARGET DRUG CONCENTRATIONS When peak and trough levels are drawn with the 4 th aminoglycoside dose (see the Monitoring section of the drug table), the levels are compared to the goal peaks and troughs to determine if dose adjustments are needed. Hospitals have protocols that guide dose adjustments. See Pharmacokinetics chapter for details. DRUG PEAK TROUGH Gentamicin Gram - negative infection 5 -10 mcg/ mL < 2 mcg/ mL Gentamicin Gram - positive infection (synergy) 3 - 4 mcg/mL < 1 mcg/ mL Tobramycin 5 - 10 mcg/ mL < 2 mcg/mL Amikacin 20- 30 mcg/ mL < 5 mcg/mL Organism-specific peak goals are typically 10 times the MIC of the bacteria causing the infection. EXTENDED INTERVAL DOSING NOMOGRAM With extended interval dosing nomograms, a random level is drawn after the first dose ( the timing depends on the nomogram; the Hartford nomogram shown below uses a window of 6 - 14 hours after the start of the infusion ) . The nomogram is used to plot the patients level and determine the appropriate dosing interval. If the level plots on a line, round up to the next dosing interval to avoid potential toxicity. . . © Nicolou DP Freeman CD et at. Antimicrob Agents and Chemother 1995 :39 :650 -655 . . 6 RxPrep Course Book | RxPrep © 2019, RxPrep © 2020 QUINOLONES Quinolones inhibit bacterial DNA topoisomerase IV and DNA gyrase (topoisomerase II ) inside the bacteria. This prevents supercoiling of DNA and promotes breakage of doublestranded DNA. Quinolones have concentration-dependent antibacterial activity and a broad -spectrum of activity against a variety of Gram -negative, Gram - positive and atypical pathogens. Some notable distinctions in the class include: are typically used in combination with another agent (e.g., a beta-lactam ) when treating Pseudomonas infections empirically. Moxifloxacin has enhanced Gram- positive and anaerobic activity and can be used alone for mixed infections (e.g., intra -abdominal infections). Moxifloxacin is the only quinolone that cannot be used to treat urinary tract infections. Gemifloxacin , levofloxacin and moxifloxacin are referred to as respiratory quinolones due to enhanced coverage of S. pneumoniae and atypical coverage. Delafloxacin, a newer quinolone approved for skin infections, is active against MRSA. Other quinolones are noted in some resources to have activity against MRSA, but because of high rates of resistance, they should generally be avoided. Ciprofloxacin and levofloxacin have enhanced Gram - negative activity, including coverage of Pseudomonas . They DRUG DOSING Ciprofloxacin (Cipro , Cipro XR , PO: 250-750 mg Q12H Ciloxan eye drops, Cetraxal IV: 200- 400 mg Q8- 12H and Otiprio ear drops) CrCI 30- 50 mL/min: Tablet, suspension, injection, Q12H ointment, ophthalmic, otic CrCI < 30 mL/min: + dexamethasone (Ciprodex Q18- 24H ) ear drops + fluocinolone (Otovel ear SAFETY/ SIDE EFFECTS / MONITORING BOXED WARNINGS Tendon inflammation and /or rupture (often in the Achilles tendon) within hours/ days of starting, or up to several months after completion of treatment: T risk with concurrent use of systemic steroids, in organ transplant patients, and age > 60 years. Discontinue immediately if symptoms occur (see Patient Counseling section). Peripheral neuropathy: can last months to years after the drug has been discontinued and may become permanent. Discontinue immediately if symptoms occur (see Patient Counseling section). Delafloxacin ( Baxdela ) PO: 450 mg Q12H CNS effects [seizures, tremor, restlessness, confusion, hallucinations, depression (and suicidal thoughts), paranoia, nightmares, insomnia,T intracranial pressure (including pseudotumor cerebri)]. Use caution in patients with CNS disorders or with drugs that cause seizures or lower the seizure threshold (see the Seizures/Epilepsy chapter). Tablet, injection IV: 300 mg Q12H Avoid in patients with myasthenia gravis (may exacerbate muscle weakness). Approved only for skin infections CrCI < 15 - 29 mL/min: dose adjustment required (IV only) Use last - line (only if no other possible treatments) for: acute bacterial sinusitis, acute exacerbation of chronic bronchitis and uncomplicated UTI (except moxifloxacin). drops) + hydrocortisone (Cipro HC ear drops) Gatifloxacin (Zymaxid eye No oral formulation QT prolongation (highest risk with moxifloxacin): avoid in patients with known QT Gemifloxacin PO: 320 mg daily Tablet CrCI < 40 mL/min: dose adjustment required Levofloxacin ( Levaquin ) PO / IV: 250- 750 mg daily Tablet, solution, injection, CrCI < 50 mL/min: extend dosing interval (Q48H) and/or i dose; adjustment varies based on indication and renal function Moxifloxacin ( Avelox , Moxeza and Vigamox eye drops) . Ciprofloxacin: concurrent administration of tizanidine drops) ophthalmic CONTRAINDICATIONS CrCI < 15 mL/min: not recommended (IV or PO) IV/ PO: 400 mg Q24H WARNINGS prolongation, or those with additive risks (hypokalemia, use of other drugs that prolong the QT interval, including Class la and Class III antiarrhythmics - see the Arrhythmias chapter). Hypoglycemia and hyperglycemia; hypoglycemia can lead to coma. Psychiatric disturbances (agitation, disorientation, lack of attention, nervousness, memory impairment and delirium). Avoid systemic quinolones in children and in pregnancy / breastfeeding due to the risk of musculoskeletal toxicity (exception: for anthrax exposure, the benefit outweighs the risk). Other: photosensitivity/phototoxicity, aortic aneurysm and dissection, hepatotoxicity, crystalluria (must stay hydrated). SIDE EFFECTS Nausea /diarrhea, headache, dizziness, serious skin reactions (SJS / TEN). Tablet, injection, ophthalmic No dose adjustment in renal impairment NOTES Cipro oral suspension - shake vigorously for 15 seconds before each use. Do not put through a NG or other feeding tube (the oil- based suspension adheres to the tubing). Ofloxacin (Ocuflox eye drops) PO: 200- 400 mg Q12H Cipro - can crush immediate - release tablets, mix with water and give via a feeding tube. Hold tube feedings at least 1hour before and 2 hours after the dose. Tablet, ophthalmic, otic CrCI < 30 mL/min: dose adjustment required Moxifloxacin does not reach adequate concentrations in the urine and should not be used for UTIs. ..a.. J •. 357 22 | INFECTIOUS DISEASES I: BACKGROUND & ANTIBACTERIALS BY DRUG CLASS Quinolone Drug Interactions Antacids and other polyvalent cations (e .g. , magnesium , aluminum, calcium , iron, zinc) , multivitamins, sucralfate , and bile acid resins can chelate and inhibit quinolone absorption . See the Patient Counseling section for more information . KEY FEATURES OF QUINOLONES Lanthanum carbonate ( Fosrenol ) and sevelamer ( Renvela ) can i the serum concentration of oral quinolones; separate administration by at least two hours before , and at least two hours after ( with lanthanum) or six hours after ( with sevelamer) . Antipseudomonal Quinolones Ciprofloxacin, levofloxacin Used for Pseudomonas infections ( including pneumonias), UTIs, intra- abdominal infections, travelers’ diarrhea (without Quinolones can T the effects of warfarin . Respiratory Quinolones Levofloxacin, moxifloxacin gemifloxacin Used for pneumonia (reliable S. pneumoniae activity) . dysentery) Moxifloxacin Only quinolone that is not renally adjusted Do not use to treat UTIs Quinolones can T the effects of sulfonylureas, insulin and other hypoglycemic drugs. IV to PO Ratio 1:1 Levofloxacin and moxifloxacin Caution with CVD, i potassium and magnesium and with other QT- prolonging drugs (e.g. , azole antifungals, Profile Review Tips Caution with CVD i K / Mg and with other QT- prolonging drugs (e.g. azole antifungals antipsychotics, methadone, macrolides) Avoid in patients with a seizure history or if using seizure drugs Avoid in children Watch for tendon rupture, neuropathy CNS or psychiatric side effects antipsychotics, methadone , macrolides ) . . . . . Probenecid and NSAIDs can T quinolone levels. Ciprofloxacin is a P-glycoprotein substrate, a strong CYP1A2 inhibitor and a weak CYP3A4 inhibitor; ciprofloxacin can T the levels of caffeine and theophylline by reducing metabolism . Counseling Avoid sun exposure, separate from cations, monitor blood glucose (DM) MACROLIDES Macrolides bind to the 50S ribosomal subunit , resulting in inhibition of RNA - dependent protein synthesis. They have excellent coverage of atypicals ( Legionella, Chlamydia, Mycoplasma and Mycobacterium avium complex) and Haemophilus . Macrolides are treatment options for community- acquired upper and lower respiratory tract infections and certain sexually transmitted infections (e.g. , chlamydia , gonorrhea ) , but utility against S . pneumoniae, Haemophilus , Neisseria and Moraxella can be limited due to increasing resistance. DRUG DOSING SAFETY/ SIDE EFFECTS /MONITORING Azithromycin ( Zithromax , Z- Pak , Zithromax Tri - Pak , AzaSite eye Z - Pak : 500 mg on day 1, then 250 mg on days 2- 5 CONTRAINDICATIONS History of cholestatic jaundice /hepatic dysfunction with prior use drops) Tri - Pak : 500 mg daily for 3 days Clarithromycin and erythromycin: do not use with lovastatin or simvastatin, pimozide, ergotamine or dihydroergotamine Tablet, suspension, injection, ophthalmic Better Gram -negative coverage than erythromycin Clarithromycin ( Biaxin , Biaxin XL ) Tablet, suspension IV: 250- 500 mg daily No dose adjustment in renal impairment PO: 250- 500 mg Q12H or 1 gram ( Biaxin XL ) daily Clarithromycin: concurrent use with colchicine in patients with renal or hepatic impairment; history of QT prolongation or ventricular arrhythmia WARNINGS QT prolongation (highest risk with erythromycin); avoid in patients with known QT prolongation, or those with additive risks (hypokalemia, use of other drugs that prolong the QT interval, including Class la and Class III antiarrhythmics - see the Arrhythmias chapter) Better Gram-positive coverage CrCI < 30 mL/min: dose adjustment required Hepatotoxicity; use caution in patients with liver disease Erythromycin ( E.E.5., Ery -Tab , Erythrocin , EryPed , Ery and Erygel topical) Dosing varies by product Clarithromycin: caution in patients with CAD ( T mortality has been documented at 1 year after the end of a 2-week course of treatment) Capsule, tablet, suspension, injection, ophthalmic, topical E.E.S = erythromycin ethylsuccinate 358 Dosing regimens vary depending on indication E.E.S 400 mg = 250 mg erythromycin base or stearate Erythromycin lactobionate is the IV form No dose adjustment in renal impairment Exacerbation of myasthenia gravis SIDE EFFECTS Gl upset (diarrhea, abdominal pain and cramping), taste perversion, ototoxicity (reversible and rare), severe (but rare) skin reactions (SJS /TEN/ DRESS) See lab interactions, storage requirements and renal dosage information near the end of this chapter. RxPrep Course Book | RxPrep © 2019, RxPrep © 2020 Macrolide Drug Interactions Erythromycin and clarithromycin are major substrates of CYP 3A4 and are CYP 3 A 4 inhibitors (moderate for erythromycin and strong for clarithromycin ) . Medications metabolized by CYP3 A4 may need to be avoided (e .g., simvastatin and lovastatin ) and others may require close monitoring, or should be used with caution in combination with erythromycin and clarithromycin . Some examples include apixaban , colchicine , dabigatran, rivaroxaban, theophylline and warfarin . Refer to the Learning Drug Interactions chapter for more information. Azithromycin is a minor substrate of CYP 3A4 and a weak inhibitor of CYP1A2 and P -gp; it has fewer clinically significant drug interactions. All macrolides: use caution with CVD, i potassium and magnesium and with other QT- prolonging drugs (e.g. , azole antifungals, antipsychotics, methadone, quinolones) . KEY FEATURES OF MACROLIDES Common Uses All macrolides: CAP, and as an alternative to a beta - lactam for strep throat Azithromycin: COPD exacerbations, monotherapy for chlamydia, combination therapy for gonorrhea, and prophylaxis for MAC: it is the drug of choice for severe travelers’ diarrhea (including dysentery, diarrhea with bloody stools) Clarithromycin: used for treatment of H. pylori (see the Gastroesophageal Reflux Disease & Peptic Ulcer Disease chapter) Erythromycin causes the most Gl upset due to T gastric motility Common Azithromycin Dosing ( Z- Pak ) Two 250 mg tablets PO xl, then 250 mg PO daily x 4 days QT Prolongation Caution with CVD, i K/ Mg and other QT- prolonging drugs (e.g., azole antifungals antipsychotics, methadone, quinolones) . Drug Interactions Clarithromycin and erythromycin are strong CYP3A4 inhibitors: lovastatin and simvastatin are contraindicated (t risk of muscle toxicity) TETRACYCLINES Tetracyclines inhibit bacterial protein synthesis by reversibly binding to the 30S ribosomal subunit. They cover many Gram positive bacteria (Staphylococci , Streptococci , Enterococci , Nocardia, Bacillus , Propionibacterium spp. ) , Gram - negative bacteria , including respiratory flora ( Haemophilus , Moraxella, atypicals) and other unique pathogens (e .g. , spirochetes, Rickettsiae, Bacillus anthracis , Treponema pallidum ) . Doxycycline has broader indications, including respiratory tract infections (e. g. , CAP) , tick - bome / rickettsial diseases, spirochetes and sexually transmitted infections (chlamydia and gonorrhea ) . Doxycycline is an option for the treatment of mild skin infections , caused by CA- MRSA, and VRE urinary tract infections. Minocycline is often preferred for skin infections, including acne . DRUG Doxycycline (Vibramycin, Doryx , Morgidox , Oracea, Acticlate, others) Capsule, tablet, suspension, syrup, injection Minocycline ( Minocin , Solodyn , CoreMino , Ximino) DOSING SAFETY/ SIDE EFFECTS /MONITORING PO/ IV: 100- 200 mg daily in 1- 2 divided doses WARNINGS Children < 8 years of age, pregnancy and breastfeeding (suppresses bone growth and skeletal development, and permanently discolors teeth) Take with food to 1Gl irritation (except take Oracea on an empty stomach 1 hr before or 2 hrs after meals) . No dose adjustment in renal impairment Photosensitivity, tissue hyperpigmentation, severe skin reactions (DRESS/SJS/ TEN) exfoliative dermatitis PO:/IV: 200 mg x 1, then 50-100 mg Q12H Gastrointestinal inflammation/ulceration (see Notes section) CrCI < 80 mL/min: max 200 mg/day Minocycline: drug-induced lupus erythematosus (PILE) Capsule, tablet, injection . SIDE EFFECTS N /V/ D, rash Eravacycline ( Xerava ) 1mg/kg IVQ12H Injection Only approved for complicated intra- abdominal infections MONITORING LFTs, renal function, CBC Omadacycline ( Nuzyra ) Dose based on indication: FDA - approved for community -acquired pneumonia and skin infections NOTES IV:PO ratio is 1:1 (doxycycline, minocycline) Dose based on body weight: approved for moderate- severe acne vulgaris Tablets and capsules should be taken with 8 oz of water: with doxycycline, sit upright for at least 30 minutes to avoid esophageal irritation Tablet, injection Sarecycline (Seysara) Tablet Tetracycline PO: 250- 500 mg Q6H on an empty stomach Capsule CrCI < 50 mL/min: dose adjustment required See lab interactions , storage requirements and renal dosage information near the end of this chapter. 359 22 \ INFECTIOUS DISEASES I: BACKGROUND & ANTIBACTERIALS BY DRUG CLASS Tetracycline Drug Interactions Antacids and other polyvalent cations (e .g. , magnesium, aluminum , calcium, iron, zinc ) , multivitamins , sucralfate , bismuth subsalicylate and bile acid resins can chelate and inhibit tetracycline absorption. Separate doses ( l - 2 hours before or four hours after) . Dairy products should be avoided 1 hour before or two hours after tetracycline . Doxycycline and minocycline can be taken with food to reduce GI upset. Dairy products are less of a concern than with tetracycline. Lanthanum carbonate ( Fosrenol ) can 1 the concentration of tetracycline derivatives; take tetracycline at least 2 hours before or after lanthanum. > KEY FEATURES OF TETRACYCLINES Common Uses Doxycycline and minocycline: CA - MRSA skin infections, acne Doxycycline: first line for Lyme disease, Rocky Mountain Spotted Fever (tick- borne illnesses), CAP CORD exacerbations, sinusitis (if an antibiotic is indicated), VRE UTI monotherapy for chlamydia, combination therapy for gonorrhea . . Tetracycline: used in H . pylori treatment (see the Gastroesophageal Reflux Disease & Peptic Ulcer Disease chapter) Do not use In pregnancy, breastfeeding or children age < 8 years Tetracycline is a major substrate of CYP 3A 4 and a moderate CYP3A4 inhibitor. Use caution with CYP 3 A 4 inhibitors, which T levels, and CYP 3A 4 inducers, which l levels. Tetracyclines can enhance the effects of warfarin and neuromuscular blocking drugs. SULFONAMIDES Sulfamethoxazole (SMX ) inhibits dihydrofolic acid formation from para -aminobenzoic acid, which interferes with bacterial folic acid synthesis. Trimethoprim ( TMP) inhibits dihydrofolic acid reduction to tetrahydrofolate, resulting in inhibition of the folic acid pathway. Sulfamethoxazole / trimethoprim covers Staphylococci ( including MRSA and CA- MRSA ); S. pneumoniae and Group A Strep coverage is unreliable . Activity against Gram - negative bacteria is broad, and includes Haemophilus , Proteus , E . coli , Klebsiella, Enterobacter, Shigella, Salmonella and Stenotrophomonas . Coverage includes some opportunistic pathogens ( Nocardia , Pneumocystis , Toxoplasmosis ) , but Pseudomonas , Enterococci , atypicals and anaerobes are not covered . DRUG DOSING SAFETY/ SIDE EFFECTS / MONITORING Sulfamethoxazole / Dose (including weight - based dosing) is based on the TMP CONTRAINDICATIONS Sulfa allergy, pregnancy (at term), breastfeeding, anemia due to folate deficiency, marked renal or hepatic disease, infants < 2 months of age Trimethoprim ( Bactrim, Bactrim DS , others) Tablet, suspension, injection component Severe Infections PO/IV: 10- 20 mg TMP/kg/day, divided Q6 -8H Single Strength (SS) 400 mg SMX/80 mg TMP (e.g , 2 DS tablets BID -TID) Double Strength (DS) 800 mg SMX/160 mg TMP 1 DS tablet PO BID x 3 days . Uncomplicated UTI Pneumocystis Pneumonia (PCP) Prophylaxis 1DS or SS tablet daily PCP Treatment IV/ PO: 15 - 20 mg TMP/kg/day divided Q6H CrCI 15 - 30 mL/min: dose adjustment required CrCI < 15 mL/min: not recommended WARNINGS Blood dyscrasias, including agranulocytosis and aplastic anemia Skin reactions: SJS /TEN, thrombotic thrombocytopenic purpura (TTP) G6PD deficiency; do not use with known deficiency and discontinue drug if hemolysis occurs Embryofetal toxicity SIDE EFFECTS Photosensitivity, T K, hemolytic anemia (identified with a positive Coombs i test), crystalluria (take with 8 oz of water), N / V/ D, anorexia, skin rash, folate, myelosuppression with prolonged use false elevations in SCr (due to inhibition of tubular secretion of creatinine), renal failure . MONITORING Renal function, electrolytes, CBC, folate NOTES See ID II chapter for a discussion on use for UTIs during pregnancy See lab interactions, storage requirements and renal dosage information near the end of this chapter. RxPrep Course Book | RxPrep 02019, RxPrep 02020 Sulfonamide Drug Interactions SMX /TMP is a moderate - strong inhibitor of CYP2C8 and CYP2C9 and can cause significantly T INR . Caution should be used in combination with warfarin (see the Learning Drug Interactions chapter for more information) . Levels of SMX /TMP can be i by CYP2C8 and CYP2C9 inducers . The therapeutic effects of SMX / TMP can be diminished by the use of leucovorin or levoleucovorin. The risk for hyperkalemia will T if used in combination with ACE inhibitors, ARBs, aliskiren, aldosterone receptor antagonists ( ARAs ) , potassium- sparing diuretics, NSAIDs, cyclosporine, tacrolimus, drospirenone -containing oral contraceptives or canagliflozin . KEY FEATURES OF SULFAMETHOXAZOLE / TRIMETHOPRIM Common Uses CA - MRSAskin infections, UTI, Pneumocystis pneumonia (PCP) 5:1 Ratio of SMX / TMP ( Dose by TMP) Single strength ( SS) tablet contains 80 mg TMP Double strength (DS) tablet contains 160 mg TMP usual dose is 1 tablet BID Sulfa Allergy Most sulfa allergies occur with SMX/TMP (rash /hives are common) Rarely, severe skin reactions (e.g., SJS or TEN) can occur; if rash is accompanied by a fever or systemic symptoms, seek emergency care INR T when used with warfarin. Use alternative antibiotic when possible. ANTIBIOTICS FOR GRAM - POSITIVE INFECTIONS VANCOMYCIN Vancomycin is a glycopeptide that inhibits bacterial cell wall synthesis by binding to the D -alanyl - D - alanine cell wall precursor and blocking peptidoglycan polymerization . Vancomycin only covers Gram - positive bacteria, including Staphylococci ( MRSA ) , Streptococci , Enterococci ( not VRE) and C. difficile ( using the PO route only ) . DRUG DOSING SAFETY/ SIDE EFFECTS / MONITORING Vancomycin (Vancocin, Firvanq oral solution) Systemic infections (IV only) IV: 15 - 20 mg / kg Q8-12H Capsule, oral solution, injection Dose based on total body weight WARNINGS Ototoxicity and nephrotoxicity; caution with use of other nephrotoxic or ototoxic drugs or with prolonged high serum concentrations (dose adjustment required in renal impairment) First -line treatment for MRSA infections Consider alternative drug when MRSA MIC 2 mcg/mL CrCI 20- 49 mL/min; Q24H CrCI < 20 mL/min: give 1 dose, then dose per levels Peripheral IV infusions should not exceed 5 mg/mL C. difficile infections (PO only) PO: 125 - 500 mg Q I D x l O days (upper end used for severe, complicated disease) No dose adjustment in renal impairment PO is used only for C. difficile colitis and enterocolitis, not for systemic infections Infusion reaction/red man syndrome (maculopapular rash, hypotension, flushing and chills from too rapid of an infusion rate - do not infuse faster than 1 gram per hour) SIDE EFFECTS Abdominal pain, nausea (oral route), phlebitis (irritation to vein), myelosuppression (neutropenia /thrombocytopenia), drug fever, severe skin reactions (SJS/ TEN) MONITORING Renal function, trough serum concentration at steady state (generally 30 minutes before the 4th or 5 th dose), WBC Goal trough: 15 - 20 mcg/mL - pneumonia, endocarditis, osteomyelitis, meningitis, bacteremia Goal trough: 10-15 mcg/ mL - other infections See lab interactions , storage requirements and renal dosage information near the end of this chapter . Vancomycin Drug Interactions The risk of nephrotoxicity is T when used with other nephrotoxic drugs ( e.g. , aminoglycosides, amphotericin B , cisplatin, polymyxins , cyclosporine, tacrolimus, loop diuretics, NSAIDs and radiographic contrast dye ) . Vancomycin can T the risk of ototoxicity when used with other ototoxic drugs ( e .g. , aminoglycosides, cisplatin , loop diuretics) . 3<