Antibiotics - Principles, Mechanisms, and Medications PDF

t1: antibiotics. 10 principles of antibiotic therapy. 1.​ accurate differential diagnosis!! --> bacterial infection, select correct antibiotic. 2.​ only treat when therapy will improve the patient's clinical course (double-edged sword)....

t1: antibiotics. 10 principles of antibiotic therapy. 1.​ accurate differential diagnosis!! --> bacterial infection, select correct antibiotic. 2.​ only treat when therapy will improve the patient's clinical course (double-edged sword). 3.​ target microbes that likely cause the diseases (give specific meds). drug resistance mechanisms: 1.​ reduce entry. 2.​ drug inactivation (ex. penicillinase from MSSA). 3.​ target mutation/protection → drug unable to bind. 4.​ expel drug. antibiotic site of action name antimicrobial spectrum adverse effects beta-lactams disrupt cell wall penicillin (ex. cloxacillin, penicillin: Streptococcus, IgE-mediated reactions (immediate). synthesis ampicillin) Corynebacterium, diphtheriae, -​ anaphylaxis spirochetes -​ angioedema, urticaria ampicillin/amoxicillin: Streptococcus, -​ IgE antibodies tend to decline Enterococcus, Listeria over time cloxacillin: methicillin susceptible S. rashes, fever. aureus (MSSA) -​ maculopapular (more common piperacillin: widest spectrum, can also with ampicillin, amoxicillin be used on gram -. with EBV, CMV) -​ SJS, related syndromes cephalosporin 1st gen: streptococci, staphylococci 4+ neurologic. -​ 1st gen: cefazolin 2nd gen: community acquired -​ seizures, myoclonus -​ 2nd gen: cefuroxime Enterobacteriaceae GI. -​ cephamycins: cefoxitin 3rd gen: penicillin resistant S. -​ diarrhea (also classified as 2nd pneumoniae -​ C. difficile-associated diarrhea gen) 3rd, 4th gen: better for gram - than other effects: -​ 3rd gen: ceftriaxone gram + bacteria -​ serum sickness (cefaclor). -​ 4th gen: cefepime -​ neutropenia. -​ interstitial nephritis → eosinophiluria, hematuria, proteinuria -​ hepatitis carbanapem used in expanded spectrum beta -​ imipenem (not for brain lactamase bacteria (ESBL), or bacteria infections, can cause resistant to 3rd gen cephalosporins. seizures). broadest spectrum, for DR-GN bacteria -​ meropenem and anaerobic bacteria. -​ doripenem imipenem: only one that works for -​ ertapenem Enterococcus faecalis. meropenem: treatment of meningitis, does not cover enterococcus. ertapenem: community-acquired organisms, including ESBL but not for Pseudomonas, Enterococcus. narrow spectrum carbapenem. beta-lactamase binds to amoxicillin/clavulanate sulbactam: bactericidal against inhibitor beta-lactamase, ampicillin/sulbactam Acinetobacter only. preventing hydrolysis piperacillin/tazobactam extended spectrum of beta-lactam. has no cefoperazone/sulbactam for drug resistant bactericidal activity, gram - bacteria, but but helps to broaden can cause severe beta-lactam spectrum collateral damage → for drug resistant (ex. drug resistance gram +, gram -, in other bacteria). Bacteroides quinolones DNA gyrase inhibitor, nalidixic acid -​ photosensitivity preventing norfloxacin -​ hypersensitivity transcription of DNA. ofloxacin -​ QT prolongation ciprofloxacin -​ peripheral neuropathy levofloxacin -​ tendinitis, tendon rupture moxifloxacin -​ CNS effects sitafloxacin -​ myasthenia gravis exacerbation -​ dysglycemia -​ very broad spectrum. macrolide protein synthesis: 50S erythromycin -​ atypical bacteria (same as -​ nausea, vomiting, abdominal inhibitor clarithromycin fluoroquinolones) pain. roxithromycin -​ Bordatella pertussis -​ abnormal liver enzyme. azithromycin -​ Corynebacterium diphtheriae -​ QT prolongation → polymorphic ventricular -​ has non-antimicrobial effect: arrhythmia. modulates innate immune response (anti-inflammatory -​ macrolide + fluoroquinolone → effect). increased risk of QT -​ given alongside other prolongation. antibiotics. clindamycin -​ gram + : strep, staph -​ diarrhea, nausea, vomiting -​ some anaerobic bacteria. -​ abdominal pain, cramps -​ NOT for Bacteroides. -​ rash, itching -​ not active against enterococci, -​ high doses → metallic taste aerobic gram - -​ topical → contact dermatitis -​ reduce bacterial toxins from strep, staph, clostridium perfringens. -​ indicated in severe infections (necrotizing skin/soft tissue, toxic shock syndrome). -​ frequent antibiotic-associated colitis (c diff). aminoglycosides protein synthesis: 30s gentamicin -​ broad range of aerobic gram - nephrotoxicity. inhibitor amikacin bacilli, including P. aeruginosa, -​ proximal convoluted tubules. netilmicin A. baumanii -​ increased renal cortical streptomycin -​ used in combination therapy accumulation of AMG with with beta-lactam for dosing frequency → increased enterococci, staphylococci peak serum concentrations. -​ x anaerobes -​ esp. in elderly, prolonged use, -​ impaired effects in acidic or DM patients, those with anaerobic environments (such as concurrent use of nephrotoxic abscesses). agents. oto-vestibular toxicity.  -​cochlear, vestibular bodies of inner ear. neuromuscular blockade. -​ interferes with neurotransmission at NMJ. -​ worsens MG. glycopeptides. disrupts cell wall vancomycin gram + bacteria! (staph, strep, -​ fever synthesis (at the end of teicoplanin enterococcus, c diff, corynebacterium, -​ rash the process), so act bacillus) -​ phlebitis slower than used in serious infections due to -​ neutropenia beta-lactams. beta-lactam-resistant gram + pathogens: -​ nephrotoxicity -​ MRSA. -​ auditory toxicity (CN8 dmg) -​ ampicillin-resistant -​ infusion-related reactions: red Enterococcus. man syndrome if drip too fast -​ (not as potent as MSSA). gram + infections with serious beta-lactam allergies. C. difficile colitis. colistin act at cytoplasmic polymyxins (only have reserved for use in big 3 gram - IV polymyxins membrane polymyxin E in thailand) -​ MDR enterobacterales -​ nephrotoxicity -​ P. aeruginosa -​ neurotoxicity: dizziness, facial -​ Acinetobacter spp paresthesis, vertigo, aerosolized polymyxins: improve neuromuscular blockade concentrations of polymyxins in distal nebulization polymyxins airway, reduce systemic toxicity -​ bronchospasm -​ cough, sore throat, chest tightness trimethoprim- inhibit bacterial trimethoprim- -​ Listeria monocytogenes (second -​ bone marrow suppression → sulfamethoxazole production of sulfamethoxazole line) neutropenia tetrahydrofolic acid -​ B. pertussis, Y. enterolitica, -​ drug allergy Aeromonas, B. cepacia -​ hyperkalemia due to inhibition -​ Burkholderia pseudomallei of K+ excretion at distal -​ stenotrophomonas maltophilia nephron -​ Nocardia -​ Pneumocystis jirovecii tetracycline protein synthesis: 30S tetracycline broad-spectrum activity (aerobic gram -​ photosensitivity inhibitor doxycycline +, -, atypical bacteria, spirochetes) -​ teeth discoloration minocycline -​ nausea, vomiting, diarrhea tigecycline doxycycline: mainly for atypical -​ hepatotoxicity bacteria, spirochetes -​ teratogenic effect (bone minocycline, tigecycline: increased development) activity against MDR gram + and gram - -​ x young children, -​ big 2: A. bomb, pregnant, breastfeeding. Enterobacterales -​ beta-lactam and vancomycin-resistant GP bacteria -​ not active against PPPM (pseudomonas, proteus, providencia, morganella) -​ active against anaerobic organisms (incl. Bacteroides) -​ not for bacteremia and UTI metronidazole causes DNA metronidazole -​ Bacteroides -​ GI: nausea, vomiting, epigastric fragmentation -​ C. diff distress  -​ protozoa -​ metallic taste combined with other antibiotics for -​ darkening of urine complicated intra-abdominal infection. -​ peripheral neuropathy *พระเอก for anaerobic bacteria* -​ pancreatitis, hepatitis -​ fever -​ reversible neutropenia bacteria beta-lactam of choice streptococci -​ penicillin/amoxicillin -​ earlier-gen cephalosporins staphylococci -​ MS: cloxacillin, 2st-gen cephalosporin -​ MR: use other drugs enterococci -​ ampicillin/amoxicillin -​ if ampicillin resistant: use other drugs enterobacterales -​ non-MD R: ampicillin/amoxicillin, earlier-gen cephalosporin, BL/BLIs -​ MD R: later gen cephalosporins, piperacillin/tazobactam, carbapenem Pseudomonas -​ 3rd gen cephalosporins, 4th gen cephalosporins, piperacillin/tazobactam aeruginosa -​ MDR-PDR: use other drug hospital-acquired -​ mostly resistant to all beta-lactams (sulbactam อาจใชไ้ ด)้ Acinetobacter bacteria active antibiotics not active antibiotics Streptococcus pyogenes penicillins non group A beta-hemolytic mostly penicillins streptococci other streptococci penicillins, cephalosporins if cannot, use clindamycin, macrolides, levofloxacin, moxifloxacin enterococci ampicillin/amoxycillin, piperacillin all cephalosporins imipenem clindamycin vancomycin (if penicillin/ampicillin R) enterobacteriaceae penicillins, cephalosporins vancomycin carbapenems clindamycin aminoglycosides fluoroquinolones polymyxins tigecycline Pseudomonas aeruginosa piperacillin ceftazidime, cefoperazone (3), cefepime (4) carbapenems except ertapenem ciprofloxacin aminoglycosides polymyxins acinetobacter baumannii susceptible: beta-lactams, fluoroquinolones, aminoglycosides mdr/xdr: polymyxins, sulbactam, tigecycline atypical pathogens macrolides fluoroquinolones (cipro, levo, moxi) tetracyclines anaerobes (Bacteroides fragilis) BL/BLIs (piperacillin/tazobactam) carbapenems tigecycline, minocycline metronidazole (combined with others)