Pharmacotherapy - Infectious Diseases PDF

Beta-lactam Antibiotics: Penicillins, Cephalosporins, Carabapenams/Monobactams Penicillins - Spectrum of Activity Penicillin G/VK Cloxacillin Ampicillin/Amoxicillin Amoxicillin/Clav Piperacillin/Tazo Gram (+) *Strept...

Beta-lactam Antibiotics: Penicillins, Cephalosporins, Carabapenams/Monobactams Penicillins - Spectrum of Activity Penicillin G/VK Cloxacillin Ampicillin/Amoxicillin Amoxicillin/Clav Piperacillin/Tazo Gram (+) *Streptococci Streptococci Streptococci Similar to amox/amp: Similar to amox/amp: *Some Enterococci (E. Staphylococci Some enterococci E. Streptococci Streptococci faecalis/faecium mostly) (MSSA,MSSE) faecalis mostly) Some enterococci E. Some enterococci E. Listeria monocytogenes faecalis mostly) faecalis mostly) No Staphylococci No enterococci Listeria Listeria monocytogenes No Staphylococci monocytogenes: Staphylococci *recent problems with *Bulky side chain (MSSA,MSSE) resistance ex. (S. projects the B-lactam *Amino group added Staphylococcus pneumoniae, ring from enzymes confers increased entry to (MSSA) S.viridians) the cell and increased *Pip/Tazo is only *Do not confuse affinity to PBP *Clavulanic acid is available IV Must be taken on an MSSA/MSSE with *Ampicillin poor absorption considered a “suicide empty stomach! [CAP] MRSA/MRSE PO and increased inhibitor” as it functions Broadest spectrum of *penicillin G incidence of skin rash and as an irreversibly activity out of all the Must be taken on an diarrhea (unlike amoxicillin) B-lacatamase inhibitor penicillin class (see empty stomach! gram (-) spectrum) [CAP] Must be taken on an empty *does have stomach! [CAP] *ampicillin dose-dependent GI *Do not confuse Does not require upset effects (diarrhea) MSSA/MSSE with renal adjustment as thus max dose in adults MRSA/MRSE it does have is 125mg/dose and in hepatobiliary children is 10mg/kg/day compensation Gram (-) Neissera meningitidis n/a Some: Enhanced activity: Enhanced activity: Treponema pallium -​ Haemophilus -​ Haemophilus -​ *Pseudomona (Sphyllius) Influenzae Influenzae s aeruginosa Corynebacterium -​ Escherichia coli -​ Escherichia -​ Haemophilus diphtheriae -​ Proteus mirabilis coli Influenzae -​ Proteus -​ Moraxella N.meningitidis mirabilis catarrhalis Borrelia burgdorferi Enhanced activity: Moraxella catarrhalis Borrelia burgdorferi -​ Enterobacterial es  Anaerobes Oral anaerobes n/a Clostridia (not C.difficile) Clostridia (not C.difficile) Closteria (not C.difficle) Clostridia (not C.difficile) Oral anaerobes Oral anaerobes Oral anaerobes Bacteroides fragilis Bacteroides fragilis Note: Table is not all-inclusive Remember: Natural Penicillin = Penicillin G/VK; Penicillinase (B-lactamase)-resistant Penicillin = Cloxacillin; Aminopenicillins = Ampicillin and Amoxicillin; Ureisopenicillin = Piperacillin (commonly combined with Tazobactam which is a B-lactamase inhibitor) Metabolism/Excretion: primarily secreted in the kidneys (intact molecule thus high levels are found in the urine despite normal kidney function) Dosage Adjustments: Majority of penicillins require renal adjustments (except for cloxacillin sue to hepatobiliary compensation) Taken on an empty stomach: Cloxacillin, Penicillin G (V?/) and Ampicillin → CAP! Adverse Effects (AE): hypersensitivity (can range from rash to anaphylaxis), CNS toxicity (seizures or when doses are not renally adjusted), transient increase in liver enzymes Drug Interactions: Oral contraceptives, when taken together (Allopurinol and Ampicillin), Probenecid (can keep serum levels high) Cephalosporins - Spectrum of Activity 1st Generation 2nd Generation 3rd Generation 4th Generation 5th Generation B-lactamase inhibitor combos Gram (+) Staphylococci (MSSA) ---------------------------------------------------------------------------------------------------> Worse Worse Similar to 1st gen Best (MRSA) Streptococci ——————————————————————————————————> Generally better as the the class of generation increases ----------------> No enterococci Gram (-) Proteus Haemophilus Haemophilus Pseudomonas *Pseudomonas Pseudomonas Enterococcus Proteus Enterobacter (Amp C (better) (ceftobiprole) H. Influenzae Klebsiella Enterococcus induction) M. catarrhalis Klebsiella Neisseria - Otherwise - Otherwise Enterobacterales M. catarrhalis Proteus similar to 3rd similar to 3rd B.burgdorferi Enterococcus generation but generation Klebsiella more stable to ampC Moraxella B-lactamases catarrhalis (such as B.burgdorferi SPICE-A  *Pseudomonas organisms) aeruginosa (ceftazidime only) Anaerobes Oral anaerobes Oral anaerobes Oral anaerobes Oral anaerobes Oral anaerobes Some anaerobic Bacetiodis fragilis Clostridia (not Clostridia (not Clostridia (not coverage but and Clostridia C.difficile) C.difficile) C.difficile) generally thought (cefoxitin) to be poor (maybe oral anaerobes) Agents Cephalexin (PO) Cefuroxime Ceftazidime (IV) Cefepime (IV) Ceftobiprole (IV) Ceftolozane- Cefazolin (IV) (PO/IV) Ceftriaxone (IV) *Ceftaroline (IV) tazobactam Cefadroxil (PO) Cefprozil (PO) Cefixime (PO) Ceftazidime - Cefoxitin (IV) Cefotaxime (IV) avibactam “Ceph, Cef, or “Furox is a pro “Taz tries to fix his Cef” fox” taxes” Note: Ceftaroline Note: Note: Cefoxitin has Note: Ceftazidime not available in Ceftolozane-tazoba good coverage of active against Canada currently, ctam better for B.fragilis, but poor Pseudomonas, but but does have the Pseudomonas and coverage of much less active best general Gram Streptococci; Haemophilus against Staph and positive activity of Ceftaz-avi better for Strep than other 3rd cephalosporins Enterobacterales gens Note: Cefixime not reliable for S. pneumoniae or S. aureus Note: Table is not all-inclusive AmpC beta-lactamases (AmpC) are enzymes which convey resistance to penicillins, second and third generation cephalosporins and cephamycins What are the AmpC producing organisms? → remember mnemonic: SPICE-A → S = Serratia; P = Providencia; I = Indole-positive Proteus (P.vulgaris); C = Citrobacter; E = Enterovacter; A = Acinetobacter (recall: Pip/Tazo does not have any activity for SPICE-A organisms) -​ Key for studying this antibiotics= look for the generations and point out the unique outliers in each class -​ Some not available in Canada Carbapenams/Monobactams - Spectrum of Activity Imipenam/Cilastatin Meropenem/Doripenem Ertapenem Aztreonam Gram (+) Most gram (+) (excluding MRSA,MRSE) E.faecalis (not faecium) Gram (-) Most gram (-) AmpC B-lactamases and ESBLS P.aeruginosa Neisseria gonorrhoeae Neisseria meningitidis Treponema pallium (Sphyllius) Legionella Anaerobes Most anaerobes (except C.difficile) *No activity against the atypicals (Mycoplasma and Chlamydia) Carbapenems gain entry to gram-negative organisms via OprD (porin), they also have improved resistance to B-lactamases Note: this iteration of b-lactam antibiotics are the broadest spectrum thus it is easier to remember what it DOES NOT cover What are ESBL bacteria? → Extended-spectrum beta-lactamases are enzymes that confer resistance to certain antibiotics (i.e. penicillins and cephalosporins) Otitis Media (OM) Otitis Media - infection and inflammation of the middle ear Relevant Risk Factors Epidemiology Clinical Presentation Diagnosis Complications Organisms S. pneumoniae Immature immune → More common in infancy Pain (earache) 2 criteria for - Perforated Ear drum H. influenzae development in children and childhood than Fever (>40.5) diagnosis: - OM with effusion (aka serous M. catarrhalis 6 weeks conjunctivitis) with myringitis; which → *recent viral illness is an inflammatory Antibiotic therapy for S. pneumoniae (i.e. common cold) condition of the complicated AOM: (less incidence → young age tympanic membrane of spontaneous → male sex (clinical presentation Cefuroxime (early-mid) x 14 resolution and → contact with other does NOT involve days complications) infected individuals fluid build up) Ceftriaxone (mid-severe) x 14 → daycare (increased days exposure) → shorter breasting Rare complications: feeding (bottle feeding when lying down flat) - Mastoiditis (infection of the → allergy mastoid bone in the skull) → smoking - Facial paralysis (environmental) - Meningitis → seasonal peaks during colder seasons Management Strategy Watchful Waiting → Monitor patient’s condition BEFORE giving any antibiotic therapy; can start therapy when symptoms change. Consider watchful waiting for the first 24 - 48 hours, UNLESS (i.e. would not do watchful waiting): 1. They have a high fever and symptoms worsen with time 2. Presenting with Complicated AOM or have history of complicated AOM) 3. Immunodeficient or comorbid conditions (i.e. cardiac or respiratory problems, or anatomical complications) 4. Follow-up period is unreasonable or caregivers are unable to recognize worsening symptoms 5. Poor response to medications (i.e. antipyretic or analgesics) for symptom management 6. Less than 6 months of age IF waiting period is recommended, can treat symptomatically using OTC (ie.advil or tylenol) → 48 - 72 hours (only if follow-up can be done) → IF not resolved then antibiotic therapy is indicated for treatment (*see below)  Overall criteria for watchful waiting: > 6 months of age Symptoms can be managed with analgesics and/or antipyretics Follow-up can be assured Initial therapy: 1st Failure of Initial therapy: The treatment is considered failed if symptoms do not resolve after 48 hours No purulent conjunctivitis of treatment initiation and No recent use of antibiotics (< 3 months), Cefuroxime > Cefprozil > Cefixime > Cephalexin Pharyngitis (URTI) Pharyngitis - Infection of the pharynx Relevant Organisms Clinical Presentation Epidemiology Diagnosis Complications S.pyogenes Bacterial etiology: Can be viral (more *it is important remember - Acute Rheumatic Fever Group A Strep testing for strep common) or bacterial in that you can not diagnose (autoimmune (B-hemolytic) origin and spread via strep based on symptoms complications) - Sore throat direct contact with alone or lab testing alone inflammatory response Viruses Fever respiratory droplets or that affects the heart, Tender/enlarged cervical secretions 1. Modified Centor joints, brain, skin, and soft lymph nodes - Strep caused by GABHS Score: the higher score tissue : Carditis and *Rash (untreated) are infectious the higher the risk of strep Arthritis are common Difficulty swallowing for 1-3 weeks 1. Fever (+1) (odynophagia) 2. Absence of cough (+1) - Peritonsillar abscess No cough High Risk Groups: 3. Tonsillitis OR - Retropharyngeal pharyngeal exudate (+1) abscess *rashes (24-48 hrs after - Children 5 -15 yrs 4. Tender anterior cervical - Otitis media onset) that are diffuse and (rare for a child 27 kg: 600 mg BID-TID Pediatrics (suspension): 50 mg/kg once or BID daily Severe allergy: Initial therapy with penicillin allergy: Clindamycin 20 mg/kg/day TID x 10 days Azithromycin 20 mg/kg x 3 days Adult: Clarithromycin 15 mg/kg/day BID x 10 days Cefuroxime 500 mg BID OR Clindamycin 300 mg daily OR Azithromycin 500 mg daily OR Clarithromycin 250 mg BID  Follow-Up: Symptoms may last 2 -7 days Follow-up cultures are not routinely done or recommended UNLESS: history of complications (rheumatic fever), persistent, recurrent symptoms *If it is viral in origin, most cases can be self-limiting so if they are experiencing symptoms of a viral infection, you would treat/manage the symptoms and allow the viral infection to resolve itself (i.e. antipyretics and analgesics etc.) *If asymptomatic carrier [test positive for strep throat] even if they don’t have symptoms: Can be a carrier based on recent exposure or a carrier for other reasons *If the individual was exposed to an infectious individual, and they started taking antibiotics within the last 24 hours, they are not considered infectious *If RADT is positive = does not require follow-up throat culture BUT if RADT is negative = recommended follow-up for children/adolescents not for adults) Sinusitis (URTI) Sinusitis (aka. Rhinosinusitis) - inflammation of the sinuses Relevant Bacteria Risk Factors Epidemiology Clinical Diagnosis Complications Presentation - Respiratory The sinuses are the 1. Fever Rare: common colds infections active apparatus for 2. Nasal congestion are rarely - Allergic rhinitis drainage in the nasal 3. Facial pain and complicated by -Immunodeficiency cavity. When not swelling (can assess bacterial sinusitis but - Tobacco, pollution drained properly and by having the patient viral infection can - Anatomical infections can occur told their head down) predispose to (deviated nasal and result in 4. Headache (or bacterial septum, tumours) inflammation migraine) complications due to - Medications 5. Cough (more the cilia are render (overuse of - The most common significant in children) immobile by viruses decongestants, illicit predisposing factor is 6. Nasal discharge drug use) viral upper respiratory (the colour of the - Trauma infection (children sputum should not be _________________ have higher incidence used to diagnosis Prevention: of infection)  - handwashing, avoiding *recall: sinusitis just environmental means inflammation tobacco smoke, of the sinus which allergen exposure, can be caused by vaccinations etc. both viral and bacterial etiology Management Strategy Pneumonia (LRTI) Pneumonia Relevant Bacteria Risk Factors Epidemiology Clinical Diagnosis Complications Presentation S. pneumoniae > 65 years of age at C. pneumoniae highest risk M. pneumoniae H. influenzae A viral infection precedes pneumonia in up to 50% of cases Management Strategy Bacterial Pathogens Gram (+) Bacteria Key Points Bacterial Pathogens (Gram-negative) Gram (-) Bacteria Key Points