Medications in Infectious Disease

CHAPTER 13 Medications in Infectious Disease Medications in Infectious Disease 13.1 Antibacterial Agents 13.2 Selected Antiviral Agents 13.3 Selected Antifungal Agents 13.4 Selected Antiprotozoal/Anthelmintic Agents 1 13.1 Antibacterial Agents 13.1 Antibacterial Agents I. Cell Wall Inhibitors Ia. Beta-Lactams 1) Penicillins 2) Cephalosporins 3) Carbapenems 4) Monobactams Ib. Glycopeptides II. Protein Synthesis Inhibitors IIa. Macrolides IIb. Aminoglycosides IIc. Tetracyclines IId. Lincosamides IIe. Oxazolidinone III. Antimetabolites Sulfonamides IV. Nucleic Acid Synthesis Inhibitors IVa. Fluoroquinolones IVb. Rifampin V. Miscellaneous VI. Clinical Pearls 2 Antibacterial Agents 13.1 I. Cell Wall Inhibitors Ia. Beta-Lactams MOA: They interfere with the last step (cross-linkage) of cell wall synthesis by binding to Penicillin binding proteins COMMENT BOX Beta-Lactams are bactericidal agents. 1) Penicillins COMMENT BOX Penicillins are considered as Pregnancy Category (B) drugs. a. Narrow Spectrum Penicillins (Natural Penicillins) (Penicillin G, Penicillin V) Route of Administration: Penicillin G (Benzylpenicillin)—IV, IM (acid-labile; not to be given orally); Penicillin V (Phenoxymethylpenicillin)—oral (on empty stomach) Coverage: Gram-positive organisms; Gram-negative cocci; nonβ-lactamase-producing anaerobes; little activity against Gramnegative rods; susceptible to hydrolysis by β-lactamases 3 Medications in Infectious Disease Side Effects: Hypersensitivity reaction (if severe, IgE-mediated then it is contraindicated); cross sensitivity; GI irritation (orally); renal failure; seizures (rare) 13.1 Antibacterial Agents b. Penicillinase-Resistant Penicillins (Antistaphylococcal) (Nafcillin, Oxacillin) Route of Administration: Nafcillin—IV, IM; Oxacillin—IV Route of Excretion: Urine or bile Coverage: Active against streptococcus and staphylococcal (resistant to hydrolysis by β-lactamases); not active against enterococci, anaerobes, and Gram-negative cocci and rods Medications in Infectious Disease c. Broad Spectrum Penicillins (Aminopenicillins) (Amoxicillin, Ampicillin) Route of Administration: Amoxicillin—oral; Ampicillin—oral (on empty stomach), IV, IM Route of Excretion: Urine Dosage Range: Amoxicillin—immediate release: 500 mg to 1 g q8-12hrs; extended release: 775 mg once daily; Ampicillin—oral: 250-500mg q6hrs; IV or IM: 1-2g q4-6hrs, max 12g/day Coverage: They retain the antibacterial spectrum of Penicillin; improved activity against some Gram-negative rods (but not Pseudomonas); relatively susceptible to hydrolysis by βlactamases COMMENT BOX Broad spectrum Penicillins should be used with caution in infectious mononucleosis patients due to an increased risk of erythematous rash. 4 Antibacterial Agents 13.1 COMMENT BOX Broad spectrum Penicillins should be used with caution in infectious mononucleosis patients due to an increased risk of erythematous rash. d. Extended Spectrum Penicillins (Piperacillin, Ticarcillin, Carbenicillin) Piperacillin/Tazobactam Medications in Infectious Disease Route of Administration: IV Route of Excretion: Urine (primarily), feces Coverage: Includes the activity of Aminopenicillin; active against P.aeruginosa and Klebsiella species Additional Side Effects: Leukopenia/neutropenia (with prolonged use) Ticarcillin/Clavulanate Route of Administration: IV Route of Excretion: Urine Coverage: Includes the activity of Aminopenicillin; active against P.aeruginosa Additional Side Effects: Hypokalemia (should be monitored) COMMENT BOX Aminopenicillins and Extended Spectrum Penicillins are susceptible to hydrolysis by β-lactamases; that is why they are often combined with β -lactamase inhibitors like Tazobactam, Sulbactam, or Clavulanate. 5 13.1 Antibacterial Agents COMMENT BOX Clavulanate does not affect the half-life of Ticarcillin. COMMENT BOX Extended Spectrum Penicillins should be discontinued if bleeding disorders occur. Beta-Lactamase Inhibitors Medications in Infectious Disease • Clavulanate—with Amoxicillin called Augmentin; with Ticarcillin called Timentin • Tazobactam—with Piperacillin called Tazocin • Sulbactam—with Ampicillin called Unasyn • Avibactam—with Ceftazidime called Avycaz MOA: They bind to and inactivate beta-lactamases and inhibit them (not all types); they have no significant anti-bacterial activity and are thus combined with other beta-lactams 2) Cephalosporins Side Effects: Hypersensitivity reaction (if severe, IgE-mediated then it is contraindicated); cross sensitivity; GI irritation (orally); renal failure; seizures (rare) COMMENT BOX Cephalosporins are similar to Penicillins but are more stable to many bacterial beta-lactamases; therefore, they have a broader spectrum of activity. They are considered as Pregnancy Category (B) drugs. 6 Antibacterial Agents 13.1 a. First Generation Cephalosporins (Cefadroxil, Cefazolin, Cefalexin, Cephalothin (prototype)) Route of Administration: Cefadroxil/Cefalexin—oral; Cefazolin— IV, IM Route of Excretion: Urine Coverage: Very active against Gram-positive cocci (streptococci and staphylococci); some activity against Gram-negative bacteria (like E coli, K.pneumoniae, Proteus mirabilis); not active against MRSA and enterococci Additional Side Effects: Cefazolin and Cefalexin are associated with increased INR Route of Administration: Cefaclor—oral; Cefuroxime—oral, IV, IM; Cefoxitin/Cefotetan—IV, IM Route of Excretion: Urine (primarily) Coverage: Same as first-generation drugs but they have extended Gram-negative coverage (Klebsiella species including those resistant to first-generation cephalosporins); active against anaerobes (Cefoxitin and Cefotetan); not active against MRSA and enterococci COMMENT BOX These drugs should be used with Caution in patients with renal impairment, colitis, and seizure disorders. 7 Medications in Infectious Disease b. Second Generation Cephalosporins (Cefaclor, Cefuroxime, Cefoxitin, Cefotetan) 13.1 Antibacterial Agents COMMENT BOX None of the first or second generation Cephalosporins is active against P.aeruginosa species. Medications in Infectious Disease c. Third Generation Cephalosporins (Ceftriaxone, Cefotaxime, Ceftazidime, Cefoperazone, Cefixime, Cefdinir, Cefpodoxime) Route of Administration: Ceftriaxone/Cefotaxime/Ceftazidime/ Cefoperazone—IV, IM; Cefixime/Cefdinir/Cefpodoxime—oral Route of Excretion: Urine (primarily), bile (Cefoperazone and Ceftriaxone) Coverage: They have expanded Gram-negative coverage compared to second-generation agents (like Haemophilus and Neisseria species); not active against MRSA and enterococci COMMENT BOX Among third generation Cephalosporins, only Ceftazidime and Cefoperazone are active against P.aeruginosa. d. Fourth Generation Cephalosporins (Cefepime, Cefpirome) Route of Administration: Cefepime—IV, IM; Cefpirome—IV Route of Excretion: Urine (Cefepime) 8 Antibacterial Agents 13.1 Coverage: Good activity against P.aeruginosa, Enterobacter (resistant to hydrolysis by β-lactamases produced by Enterobacter unlike second and third generations which are facing newly-emerging resistance against this species), and S pneumoniae; highly-active against Haemophilus and Neisseria; not active against MRSA and enterococci Additional Side Effects: Positive direct Coombs test (hemolytic anemia); neurotoxicity; increased INR Medications in Infectious Disease e. Fifth Generation Cephalosporins (Ceftaroline Fosamil) MOA: Cell wall inhibitor through inhibition of PBP2a Route of Administration: IV (slow infusion) Route of Excretion: Urine Coverage: Active against MRSA; some in-vitro activity against enterococci; some Gram-negative activity (but not active against pseudomonas or ESBL) Additional Side Effects: Positive direct Coombs test 9 13.1 Antibacterial Agents 3) Carbapenems (Imipenem, Meropenem, Ertapenem, Doripenem) Side Effects: Hypersensitivity (because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty); seizures COMMENT BOX Meropenem, Ertapenem, and Doripenem are considered as Pregnancy Category (B) drugs, while Imipenem is considered as Pregnancy Category (C) drug. Medications in Infectious Disease Imipenem/Cilastatin Route of Administration: IV infusion only Route of Excretion: Urine (primarily) Half-life: 60 mins Coverage: Active against most Gram-negative rods (including P.aeruginosa); Gram-positive organisms; anaerobes Additional Side Effects: Decreased hematocrit and hemoglobin; thrombocytopenia; increased AST and ALT; CNS effects COMMENT BOX Imipenem is metabolized in the kidney to produce toxic metabolites; Cilastatin prevents that metabolism. Meropenem Route of Administration: IV Route of Excretion: Urine (primarily) Half-life: 60 mins 10 Antibacterial Agents 13.1 Coverage: Similar to Imipenem with slightly greater activity against Gram-negative aerobes and slightly less activity against Gram-positives Additional Side Effects: Can rarely cause CNS effects and dermatological effects (Stevens-Johnson syndrome and toxic epidermal necrosis) Ertapenem 4) Monobactams (Aztreonam) Route of Administration: IV, IM Route of Excretion: Urine (primarily) Coverage: Limited to aerobic Gram-negative organisms (including P.aeruginosa); no activity against Gram-positive bacteria or anaerobes (unlike other β-lactam antibiotics) Side Effects: Neutropenia; increased serum transaminases COMMENT BOX Monobactams are considered as Pregnancy Category (B) drugs. 11 Medications in Infectious Disease Route of Administration: IV infusion, IM Route of Excretion: Urine (primarily) Half-life: 4 hours (advantage of being given once daily) Coverage: Similar to other carbapenems but does not have activity against P.aeruginosa, Acinetobacter, Enterococcus spp., and Penicillin-resistant strains of S.pneumonia Additional Side Effects: GI effects (diarrhea) 13.1 Antibacterial Agents Ib. Glycopeptides (Vancomycin, Teicoplanin) COMMENT BOX IV Vancomycin is considered as Pregnancy Category (C) drug, while oral Vancomycin and Teicoplanin are considered as Pregnancy Category (B) drugs. Medications in Infectious Disease Vancomycin MOA: Binds to the D-ala-D-ala portion of cell wall precursor, preventing glycopeptide polymerization Route of Administration: IV, PO, rectal (off-label) Route of Excretion: IV—renal; PO—fecal (primarily) Coverage: Gram-positive species including MRSA and other Gram-positive anaerobes including C.difficile Side Effects: PO—abdominal pain; dysgeusia (solution); nausea; IV—Cardiovascular (hypotension with rapid IV administration less than 1.5 hours); red man syndrome; nephrotoxicity; ototoxicity; neutropenia; thrombocytopenia COMMENT BOX Vancomycin displays time-dependent antimicrobial killing activity (slowly bactericidal). However, it has no activity against Gram-negative bacteria because of its huge structure that prevents it from penetrating the outer membrane of these organisms. 12 Antibacterial Agents 13.1 II. Protein Synthesis Inhibitors IIa. Macrolides MOA: Inhibition of protein synthesis via binding to the 50S ribosomal subunit Side Effects: They have been associated with rare Qt prolongation and ventricular arrhythmias COMMENT BOX Macrolides are mainly bacteriostatic agents. Erythromycin Medications in Infectious Disease Route of Administration: Oral, IV (infusion only) Route of Excretion: Fecal (primarily) Coverage: Gram-positive bacteria (especially pneumococci, streptococci, staphylococci, and corynebacteria); Mycoplasma pneumoniae; Chlamydia trachomatis; H pylori; Gram-negative organisms such as Neisseria species Additional Side Effects: Signs of liver disease COMMENT BOX Erythromycin may be bactericidal at higher concentrations. Azithromycin Route of Administration: IV (infusion), oral Route of Excretion: Fecal (primarily) Coverage: Slightly less active than Erythromycin against staphylococci and streptococci and slightly more active against H influenzae 13 13.1 Antibacterial Agents Additional Side Effects: Diarrhea; nausea; abdominal pain; use with caution in patients with renal disease, liver disease and cholestatic jaundice (especially associated with prior Azithromycin use), and myasthenia gravis COMMENT BOX Azithromycin should not be given long-term to prevent bronchiolitis obliterans syndrome in patients with cancers of the blood or lymph nodes who undergo stem cell transplant because of increased rate of relapses of hematological malignancies and death. Medications in Infectious Disease Telithromycin Route of Administration: Oral Route of Excretion: Urine Coverage: Has better activity against macrolide-resistant species of S.pneumoniae, staphylococci, enterococci, Chlamydia trachomatis, and Neisseria gonorrhoeae Additional Side Effects: GI effects (Diarrhea) Contraindications: Myasthenia gravis (risk of respiratory failure) COMMENT BOX Azithromycin and Erythromycin are considered as Pregnancy Category (B) drugs. Telithromycin, however, is considered as Pregnancy Category (C) drug. 14 Antibacterial Agents 13.1 IIb. Aminoglycosides (Tobramycin, Gentamicin, Amikacin, Streptomycin) COMMENT BOX Aminoglycosides have a concentration-dependent bactericidal effect and a significant post-antibiotic effect. They are considered as Pregnancy Category (D) drugs. COMMENT BOX Aminoglycosides are almost always used in combination with a βlactam antibiotic to extend empiric coverage and to take advantage of the potential synergism between these two classes. 15 Medications in Infectious Disease MOA: Inhibition of protein synthesis via binding the 30S ribosomal subunit Route of Administration: IV infusion, IM Route of Excretion: Urine Coverage: Mainly Gram-negative bacteria (including P.aeruginosa); Amikacin is resistant to many enzymes that inactivate Gentamicin and Tobramycin and has slightly better activity than them; Streptomycin is not currently useful due to developing resistance in most species with the exception of a few like M.tuberculosis (second-line agent) and Brucella Side Effects: Neurotoxicity (ototoxicity, irreversible); nephrotoxicity (usually reversible); neuromuscular blockade; local skin reactions with IM injection (should be administered in a large muscle) 13.1 Antibacterial Agents IIc. Tetracyclines Medications in Infectious Disease (Tetracycline, Minocycline, Doxycycline, Tigecycline) MOA: Protein synthesis inhibition via binding to the 30S ribosomal subunit Route of Administration: Tetracycline—oral (on empty stomach); Doxycycline/Minocycline—oral, IV; Tigecycline—IV only Coverage: Broad spectrum including Gram-positive (including MRSA) and Gram negative bacteria, certain anaerobes, rickettsia, chlamydia, and mycoplasmas (Tigecycline has an improved activity compared to other Tetracyclines) Side Effects: GI discomfort; light hypersensitivity; permanent teeth discoloration (in children); increased BUN; hepatotoxicity (more with Tetracycline and Minocycline than Doxycycline); tissue hyperpigmentation (with Doxycycline); autoimmune syndromes (with Minocycline) Contraindications: Severe hepatic dysfunction; pregnancy 2nd and 3rd trimesters (although recent data supported the use of these drugs in some cases of pregnant women with lifethreatening infections); breast feeding; children less than 8 years; avoid administration along with dairy products and divalent cations (Ca+2, Mg+2, Fe+2, Al+3) COMMENT BOX Tetracyclines are bacteriostatic agents. They are also considered as Pregnancy Category (D) drugs. 16 Antibacterial Agents 13.1 IId. Lincosamides (Clindamycin, Lincomycin) MOA: Protein synthesis inhibition via binding to the 50S ribosomal subunit Route of Administration: Clindamycin—oral, IV (never administer undiluted as bolus), IM; Lincomycin—IV, IM, subconjunctival injection Coverage: Active against Gram-positive bacteria (esp. streptococci, staphylococci (including MRSA), and pneumococci); not active against Enterococci and Gram-negative aerobic organisms Side Effects: Colitis (C.difficile-associated diarrhea); hypersensitivity; impaired liver function Medications in Infectious Disease COMMENT BOX Clindamycin is considered as Pregnancy Category (B) drug, while Lincomycin is considered as Pregnancy Category (C) drug. They both are bacteriostatic agents. IIe. Oxazolidinones (Linezolid) MOA: Binds to the ribosomal RNA of the 50S subunit Route of Administration: Oral, IV (do not mix or infuse with other medications) Route of Excretion: Urine, feces Coverage: Active against Gram-positive organisms (including staphylococci, streptococci, enterococci, and Gram-positive anaerobic cocci); also active against M.tuberculosis 17 13.1 Antibacterial Agents Side Effects: Diarrhea; bone marrow suppression (decreased WBCs, RBCs, and platelets); skin reactions; neuropathy; serotonin syndrome (increased risk when used with other serotonergic agents) Contraindications: Concurrent use or within 2 weeks of MAOinhibitors; hypertensive patients; patients with carcinoid syndrome COMMENT BOX Medications in Infectious Disease Linezolid is bacteriostatic against enterococci and staphylococci and bactericidal against most strains of streptococci. It is considered as Pregnancy Category (C) drug. III. Antimetabolites (Sulfonamides combinations) Sulfamethoxazole (SMX)–Trimethoprim (TMP) or CoTrimoxazole MOA: They inhibit the formation of tetrahydrofolate (THF) Route of Administration: Oral, IV Route of Excretion: Urine Coverage: Active against Gram-negative (esp. Salmonella and Shigella); most Gram-positive especially Nocardia and Listeria (also including MRSA but not streptococcus group A); Pneumocystis jiroveci Pneumonia Side Effects: GI upset; crystalluria; hepatotoxicity; hyperbilirubinemia; hyperkalemia; use during the last 2 weeks of pregnancy is associated with increased risk of neonates with prolonged physiological jaundice 18 Antibacterial Agents 13.1 Contraindications: Hypersensitivity to any sulfa drug; concomitant use with other sulfonamides; blood dyscrasias COMMENT BOX Each one of SMX or TMP is bacteriostatic when used alone; however, when combined, they are often bactericidal. SMX-TMP is considered as Pregnancy Category (C) drug. IV. Nucleic Acid Synthesis Inhibitors IVa. Fluoroquinolones First Group—Norfloxacin Second Group—Ciprofloxacin, Levofloxacin, Ofloxacin, Enoxacin • Third Group—Gemifloxacin, Moxifloxacin, Gatifloxacin MOA: They inhibit bacterial DNA gyrase and topoisomerase IV Route of Administration: Oral, IV infusion Route of Excretion: Mixed (renal and nonrenal) Coverage: Generally, they have excellent Gram-negative coverage and variable Gram-positive coverage; • First group—least active against both Gram-negative and Gram-positive organisms • Second group—excellent Gram-negative activity (including P.aeruginosa, with Ciprofloxacin being the most active) and moderate to good Gram-positive activity (including S.pneumonia, with Levofloxacin being the most active) 19 Medications in Infectious Disease • • 13.1 Antibacterial Agents • Third group—improved activity against Gram-positive organisms (esp. S pneumoniae) and atypical pneumonia agents like Chlamydia, Mycoplasma, and Legionella (alongside Levofloxacin, they are called Respiratory Fluoroquinolones) Side Effects: Hypersensitivity; QT prolongation; dysglycemia; hepatotoxicity; phototoxicity; CNS effects; peripheral neuropathy; GI effects; psychiatric effects; mental illness; tendonitis and tendon rupture (DC in patient who display these effects) Contraindications: Previous tendonitis associated with quinolones use; concomitant administration with antacids, dairy products, and metal cations Medications in Infectious Disease COMMENT BOX Fluoroquinolones have many drug-drug interactions. Also, their side effects can be irreversible. All of this largely participated in discouraging their use in practice in case a less toxic alternative is available. IVb. Rifampin/Rifampicin MOA: Blocks RNA transcription via binding to RNA polymerase Route of Administration: Oral (on empty stomach), IV infusion Route of Excretion: Feces (primarily), urine Coverage: Active against Gram-positive organisms; some Gramnegative organisms (including Neisseria and Haemophilus species); also active against M.tuberculosis and Brucella Side Effects: Rash; thrombocytopenia; nephritis; flu-like symptoms; orange-colored urine, sweat, and tears (harmless) COMMENT BOX Rifampin is a bactericidal agent. It is considered as Pregnancy Category (C) drug. They also have a lot of drug-drug interactions. 20 Antibacterial Agents 13.1 V. Miscellaneous Fosfomycin MOA: It is a phosphonic acid derivative that Inactivates the enzyme pyruvyl transferase, which is critical in the synthesis of cell walls by bacteria Route of Administration: Oral, IV Coverage: Has activity against both Gram-positive and Gramnegative organisms Side Effects: Headache; diarrhea; vaginitis COMMENT BOX Nitrofurantoin MOA: Nitrofurantoin is reduced by bacterial flavoproteins to reactive intermediates that inactivate or alter bacterial ribosomal proteins Route of Administration: Oral (with meals) Coverage: Active against E. coli, Enterococci, Staphylococcus aureus, and certain strains of Klebsiella and Enterobacter species Side Effects: Anorexia; nausea; vomiting COMMENT BOX Nitrofurantoin is considered as Pregnancy Category (B) drug. 21 Medications in Infectious Disease Fosfomycin is considered as Pregnancy Category (B) drug. 13.1 Antibacterial Agents Isoniazid MOA: Inhibition of mycolic acid synthesis (an essential component of cell wall) Route of Administration: Oral (on empty stomach), IM Coverage: M.tuberculosis Side Effects: Increased serum transaminases; risk of hepatitis and pancreatitis; peripheral neuropathy (usually given with Vitamin B6) COMMENT BOX Medications in Infectious Disease Isoniazid is considered as Pregnancy Category (C) drug. Ethambutol MOA: Inhibits arabinosyl transferase resulting in impaired mycobacterial cell wall synthesis Route of Administration: Oral Coverage: Mycobacterial species (combined with other agents) Side Effects: Visual disturbances (including color blindness, visual field defects, and optic neuritis) COMMENT BOX Ethambutol is considered as Pregnancy Category (B) drug. 22 Antibacterial Agents 13.1 VI. Clinical Pearls • • • • • 23 Medications in Infectious Disease • In this section, we will mention briefly the antimicrobials that are used empirically in certain site-specific infections It is important to weigh-out risk against benefit before starting empirical antimicrobial therapy, and to do cultures to establish the particular microbial diagnosis when possible Once the causative organism and its susceptibility for antimicrobials are identified, the antimicrobial regimen should be narrowed down to the narrowest possible coverage Note that the choice of antimicrobial agents should be guided by the common microorganisms causing the disease and their susceptibility to different antimicrobials in that specific community or hospital according to data collected as well as the clinical status of the patient, site of infection, and drug properties (e.g. site penetration) Certain antimicrobials have synergistic effects when combined together The treatments that we will mention are typically the firstline regimens for immunocompetent adults (unless otherwise mentioned) 13.1 Antibacterial Agents 1) Bacterial Meningitis/Meningoencephalitis Choice of Empirical Antimicrobial: • Medications in Infectious Disease Community acquired (in immunocompetent patients <50 years)—Third Generation Cephalosporin + Vancomycin • Healthcare acquired (greater coverage of gram negative is required)—Vancomycin + Meropenem or Ceftazidime or Cefepime Common Causative Microbes: Pneumococcus, Meningococcus, H.influenza, herpes, CMV Duration of Treatment: Typically 7-21 days depending on causative organism and clinical status of patient COMMENT BOX Add Ampicillin for patients >50 year old to cover L. Monocytogenes. If encephalitis is present, herpetic infection should be suspected and patient should be started on Acyclovir (it can be difficult to differentiate between meningitis and encephalitis). COMMENT BOX Moxifloxacin can be used in patients with Penicillin or Cephalosporin allergy. 24 Antibacterial Agents 13.1 2) Sinusitis/Acute Otitis Media Choice of Empirical Antimicrobial: Amoxicillin-clavulanate; others include Doxycycline and Fluoroquinolones Common Causative Microbes: Streptococcus pneumonia, H.influenza, Moraxella catarrhalis Duration of Treatment: Typically 5-10 days 3) Pneumonia Community Acquired Pneumonia (CAP) Inpatient 3-drug regimen: Beta-Lactam No risk factors (1): First-line: (Beta-lactam or antipseudomonal Macrolide or DoxycyCarbapenem) + (Macrolide or (e.g. Ceftazidime cline respiratory Fluoroquinolone) or Imipenem or Risk factors (2): (Beta- Suspected Pseudomonas (3): Piperacillinlactam + Macrolide) (Levofloxacin/Ciprofloxacin + Tazobactam) + or a respiratory Fluoro- Carbapenem) or (Piperacillin- Anti–MRSA quinolone Tazobactam) or Cefepime or (Vancomycin or (Levofloxacin + AminoglycoLinezolid) + Amiside + Aztreonam) (4) noglycoside (e.g. Amikacin) Suspected MRSA (5): add Vancomycin or Linezolid to the above regimen (1): Immunocompetent patient, no comorbidities, bacterial resistance less than 26%, and no use of antibiotics in the last 3 months (2): e.g. COPD (3): e.g. COPD, Gram-negative bacilli in sputum (4): The last regimen is used in case of Penicillin allergy (5): e.g. recent influenza infection 25 Medications in Infectious Disease Outpatient Hospital Acquired Pneumonia 13.1 Antibacterial Agents Common Causative Microbes (CAP): Streptococcus pneumonia, Chlamydia, Mycoplasma, Legionella, viral; more virulent organisms include Staphylococcus, Pseudomonas, Enterobacteria, and certain strains of influenza virus Duration of treatment: 7-10 days (can be longer); CAP—typically 5 days (3 days for Azithromycin 500 mg) COMMENT BOX Avoid using Fluoroquinolones in the outpatient treatment of CAP if possible to slow the development of microbial resistance against these drugs. COMMENT BOX Medications in Infectious Disease Macrolides and Fluoroquinolones have high oral bioavailability so they can be used in patients orally rather than parentally. 4) Infective Endocarditis Choice of Empirical Antimicrobial: Varies; as per culture (blood cultures are typically positive in more than 90% of cases and empirical antibiotic is not necessary if the patient is clinically stable) Common Causative Microbes: MRSA, MSSA, Enterococci, Streptococci, HACEK, Brucella Duration of Treatment: Typically 6 weeks, but can be shorter in uncomplicated right-sided IE or with less virulent organisms COMMENT BOX Once cultures are positive, treatment options include Penicillin G +/Gentamycin or Ceftriaxone for S.Viridans, Nafcillin for MSSA or coagulase-negative Staphylococcus, Vancomycin for MRSA, and Gentamycin + Ampicillin or Vancomycin for Enterococcus. 26 Antibacterial Agents 13.1 5) Septic arthritis Choice of Empirical Antimicrobial: Typically Vancomycin + third generation Cephalosporin (Vancomycin can be substituted with Clindamycin in clinically stable patients aged >3 months) if sensitive organism) Common Causative Microbes: MRSA, Enterobacteria, Gonococcus, H.influenza Duration of Treatment: 3-4 weeks in adults COMMENT BOX Cefepime must be used instead of third generation Cephalosporin in case P.aeruginosa is suspected (e.g. in patient with history of penetrating injury). Medications in Infectious Disease COMMENT BOX Joint aspiration and blood cultures should be sent before starting antibiotic therapy if possible. IV antibiotic therapy is then started until the patient is clinically stable. After the patient reaches a good clinical status, therapy can be then switched to oral as outpatient (as per culture). 6) Osteomyelitis Choice of Empirical Antimicrobial: Typically Vancomycin + third generation cephalosporin or Cefepime (as per culture) Common Causative Microbes: Staphylococcus, Gram-negatives Duration of Treatment: Typically 8 weeks (IV) in adults 27 13.1 Antibacterial Agents COMMENT BOX An attempt for surgical debridement is typically done before antibiotic therapy to allow better penetration of the antimicrobial agent by removing necrotic tissue, and for sampling to establish microbiological diagnosis. COMMENT BOX The treatment varies if a prosthesis is present, which if not removed surgically could involve added Rifampicin for its great biofilm penetrance (for S.aureus). 7) Cellulitis Medications in Infectious Disease Choice of Empirical Antimicrobial: Cefazolin (IV) or Cephalexin (oral). If there is pus or an abscess, MRSA should be covered (Vancomycin or Clindamycin or Linezolid) Common Causative Microbes: Group B Streptococcus, Staphylococcus Duration of Treatment: Typically 5-14 days COMMENT BOX Choice of oral vs. IV therapy should be guided by the clinical status of the patient and the presence of risk factors (severely ill or immunocompromised patients should receive IV antibiotics). COMMENT BOX If there is an abscess, it should be drained first and the antibiotics may or may not be initiated depending on the clinical picture. 28 Antibacterial Agents 13.1 Antibiotic groups according to their activity against specific microorganisms Anti-pseudomonas activity Anti-MRSA activity Anti-TB activity Carbapenems (NOT Ertapenem) Glycopeptides (Vancomycin, Teicoplanin) Rifampicin Aminoglycosides Ceftaroline Fosamil Isoniazid Ticarcillin/Clavulanate, Piperacillin/Tazobactam SMX-TMP Ethambutol Monobactams Clindamycin Pyrazinamide Medications in Infectious Disease Third generation CephaTetracycline (Tigecycline, losporin (Ceftazidime minocycline) and Cefoperazone) Streptomycin Cefepime Linezolid Fluoroquinolones Ciprofloxacin Rifampicin Aminoglycosides Colistin Daptomycin Para-amino salicylic acid 29