B-Lactam antibiotics 1-10% allergy, IV injection with lots of Na/K, beware in renal impairment, Cholestatic jaundice Penicillin Penicillin

G IV: Immediate 3-6MU Q4-8H (total peak, IM: peak 12-30MU/day) 15-30 min Short t1/2: 0.5 hr
2-4 MU Procaine

Frequency dependent

G (+); G (-) Neisseria meningitides Anaerobe (actinomyces Israeli, Clostridium perfringens) X Enterobacteriaceae (almost all resistant) X GPC and CNB anaerobes (B-lactamase)

Strep infection; Meningococcal Syphilis; Anthrax; Actinomycosis Clostridial infection; Listeria monocytogenes1 Syphillis Rheumatic fever prophylasix Strep pharyngitis treatment For sore throat

penicillin IM, peak 1-4hr, Tubular secretion of penicillin blocked by duration 15hr probenecid IM, duration 2128Ds Oral Resists gastric acid breakdown

1.2- 2.4MU single Benzathine dose penicillin 500-750mg q6h Penicillin V

Penicillinase resistant penicillin

(modified B-lactam ring) Cloxacillin (Orbenin) Methicillin, Nafcillin, Oxacillin Dicloxacillin Flucoloxacillin 250-500mg Q6H po Ampicillin Amoxillin (Amoxil)

Bioavaliability of cloxacillin 40% only MSSA treat for endocarditis, change to oral not good enough if cellulites, change oral to Keflex (1st cepha) GI upset

Excrete both biliary and urine (No adjust dose)

Bioavailibility of Amoxillin better (75% v.s. 30%) If change to oral, use amoxillin Rash with IM injection. GI upset Tazocin better than Timentin; May add with aminoglycoside synergistic action Previously better in G(-), now much resistance Timentin not much use: if worry about Pseudomonas, use sulperazone, meroneum, piperazillin; If not use rocephin, claforen

Extended spectrum penicillin

Antipseudomonal Tazocin 2.25-4.5 Q6-8H

(carboxypenicillin) = piperacillin 4g + tazobactam 500mg

Timentin 1.6-3.2g Q6-8H

= Ticarcillin 3g + clavulanate 200mg

B-lactamase inhibitor

Human/animal bite wounds (375mg= 250+125; 1g = 875+125) MSSA (penilliniase producing S aureus) CAP, Acute exacerbation of COAD (Syrup 5ml 125+31.25)/ (IV1.2g=1g+200) B-lactamase producing G (-) Aspiration pneumonia 375-750mg BD Unasyn prodrug sultamicillin Anaerobes including B fragilis UTI; Intra abdominal infection Tazocin, timentin 375mg Ampicilin 220mg + sulbactam 147mg (NOT to all resistance e.g. NOT for pneumococci/ gonococci) DM foot infection (poor blood anaerobes)
(better in treating acinobacter infection)

Augmentin Amoxillin + clavulanic acid

No need add flagyl to cover anaerobes if used

Sulperazon sulbactam 500mg+

cefoperazone 500mg; 12g Q12H Carbapenem Imipenem 500mg q6h Renal excretion Tienam = imipenem 55-60% 500mg + cilastatin 500mg Good to CSF Meropenem 1g Q8H Slow infusion Potent activity against GP + GN, aerobic + anerobic Anti-pseudomonal activity +ve. BUT not cover MRSA Stable to most B lactamases, including ESBL ESBL GNB infection
Infections caused by path resistance to others

Menigitis NOT use tienam (cause seizure)

Prophylaxis for necrotizing pancreatitis Neutropenic fever

Cephalosporins - Most excreted in kidneys in unchanged form good in UTI, reduce dose in renal failure - Excreted in bile: cefoperazone (sulperazon), ceftriazone (rocephine) NO NEED FOR REDUCE DOSE - GPC: OK for streptococci; stable to MSSA (decreased activity with highter generation); NOT for: MRSA, Enterococci, Listeria monocytogenes) - GNB: OK for GNB - Only ceftazidime (Fortum), Cefoperazone (Sulperazon), Cefepime (Maxipime) have anti-pseudomonal activity - NOT cover anaerobes 1st Cefazolin (IV) 1gQ8H Cephalexin (Keflex, oral) Cefuroxime (Zinacef/ Zinnat) Cefoxitin (Mefoxin) Ceftibuten (Cedax) 400mg daily Cefprozil (Procef) 500mg daily

>90% bioav
Zinnat only 50% bioav oral change to augmentin

Stable against staphylococcal B-lactamase MSSA, Streptococcus pyogenes Stable to most B-lactamase GAS, pneumoncoccus, MSSA (less than 1st) H influena, M catarrhalis, E coli, Klebsiella NOT anaerobes Stable to most B-lactamase Potent against GPC and GN Hydrolyzed by ESBL Good BBB penetration if inflamed Claforan: T1/2 ~ 1 hr (need Q8H) Rocephin: T1/2 ~ 6-9hrs, biliary excretion

Cellulitis (better oral availability than Cloxacilin)

Surgical prophylaxis UTI CAP Soft tissue infection Intraabdominal infec (+ flagyl to cover anaerobes) Surgical prophylaxis CAP Meningitis Intra-abdominal infection Osteomyelitis Typhoid fever UTI Neonatal sepsis More against P. aeuroginosa, Burkhoderia cepacia

2nd

3rd

Cefotaxime (Claforan) 1g BD Rocephin Ceftriaxone (Rocephin) 2g QD/BD better as Ceftibuten (Cedax, oral)

less freq dose cheaper

Ceftazidime (Fortum) 1g TDS

LESS USE

Strong inducer of ESBL, expensive

Cefoperazone (500mg+sulbactam 500mg Sulperazon) 2-4g/D iv Q12 4th Cefepime (Maxipime) 1.5-1g Q12H, 2g Q8H Cefditoren, Defpirome

NOT for meningitis

If not with sulbactam not reliable activity Less induce ESBL better than fortum

Moderate against P aeuroginosa Less stable to enterobacterial B lactamases NOTE: all not cover MRSA, Enterococci, Listeria, Anaerobes (except sulperazone) 2nd-3rd G: NOT cover MSSA If blood C/ST +ve, need to add cloxacillin to cover

Gp of cephamycin e.g. cefoxitin, cefmetazole, cefminox Some anaerobic effect. More resistance to Blactam than other true2nd generation

Aminioglycosides
Streptomycin, Gentamicin, Amikacin, Tobramycin, Netilmicin, Neomycin Once daily dose: 1. Concentration dependent killing 2. May reduce occurrence of toxicity (saturable transport system occupied at high conc) Rapid bactericidal, protein synthesis MOST aerobic GNB Some GPC (need + B-lactam, de to synergistic effect with cell wallactive agents) NO anaerobic Antimycobacterial activity (TB, MAI) Seldom use along except UTI due to potential toxicity Very poor oral absorption - All equal Gentamicin: less expensive Rapid absorb after IMI or serious cavity Nosocomial acquired Poor penetration to cells, lung CSF - Tobramycin (P aeruginosa) T1/2 ~ 2 hrs - Amikacin: lowerest resistant rate Excreted by glomerular filtration Very high conc in renal cortex Suspect or documented CN septicemia (pyelonephrotis)
Community acquired GNB: Enterococcal endocarditis GPC prosthetic valve infection Pneumonia with GNB (with B-lactam) UTI/pyelonephritis Bone infection

S/E 1. Ototoxicity: irreversibel - Auditory: higher freq tone then speak Tinnitus, fullness, bilateral - Vestibular: vomiting, nystagmus, vertigo, dizziness 2. Nephrotoxicity: mild and reversible 8%

Glycopeptides vancomycin 1g BD/ 750mg BD in elderly, teicoplanin (Targocid) 400mg Q12H

(For G+ cocci, NO G-ve effect) Inhibits 2nd stage of cell wall formation; B-lactam inhibit 3rd stage different site of action lack of cross-resistance Frequency dependent: usual dose 1gm Q12H (if obese, burn increase freq) (better to reduce dose than to incrase dosage interval) Penetrate well Variable in CSF Excreted by kidneys (t1/2 in anephric pt >7D) Red man sydrome USE: 1.B-lactam resistant GP 2.allergy to B-lactam GP: - most GPC (Staph, Strep), except enterococci (inhibited, bactericidal with combined with aminoclycoside) - Less active than Cloxacillin against MSSA -less active than penicillin again Penicillin-sus sstrep No activity again GN Anaerobic: Active against anaerobic and microaerobic streptococci, clostridia No activity against GN anaerobes
Only monitor trough level, if renal function normal at 3rd dose)

Trough level ~ 10mg/L 7umol For serious infection 15-20mg/L 15umol Indication for monitoring - severe burn patient - morbid obesity - renal impairment - serious infections e.g. prosthetic valve infection

Fluoroquinolones (FQ) Nalidixic acid, ciprofloxacin, levofloxacin (cravit), New: moxifloxacin

Concentration dependent Act on 2 site: 1. DNA gyrase, 2. topoisomerase IV (old FQ: if one mutation resistance; new FQ, new 2 mutation but still easy) Moxifolxacin: respiratory FQ (better killing on strep pneumonia), enhanced activity against G (+) cocci and anaerobes High resistance rate rate Use: 1. UTI, CAP (less good in HK due to high prevalence of pTB) 2. 2nd line agent of pTB 3. Others: STD, travel diarrhea, enteric fever (but high resistance rate) S/E: GI upset, Liver toxicity (trovofloxacin); CNS toxicity (1-4%, alteration of mood, anxiety, depression, seizures); QT prolong (torsades de pointes), tendon rupture (Achilles tendon if >50 you, use steroid also); affect developing cartilage and fetus not in pregnancy, young children

Macrolides
Gp 1 (14-member ring): clarithromycin (Klacid), erythromycin, roxithromycin Gp 2 (16-member ring): leucomycin, rokitamycin, spiramycin Gp 3 (15-member ring): azithromycin (zithromax) Activity: 1. Most GPC 2. Neisseria spp. Haemophilus spp., Bordetella pertussis, Moraxella catarrhalis 3. Against intracellular pathogens: chlamydia trachomatis, Chlamydophila pneumoniae, Legionella pneumophila, MAC, Rickettsia spp. Ureaplasma urealyticum, Mycoplasma spp. Samonella spp. Borrelia burgdorferi (Lyme disease) Poor activity against Enterobacteriace and pseudomonas, enterococci Clinical use: atypical pneumonia, MAC, H pylori, STD (chlamydia) GPC, Rickettisal infections, Lyme disease, Salmonella, Pertussis, Camylobacter jejuni Erythromycin/ klacid met by cytochrome p450 T 1/2 Dose Erythromycin/ klacid -> haptic enzyme induction Klacid also by renal Erythromycin Azithromycin excreted via feces Klacid Liver failure: avoid erythromycin (other 2 no change) Azithromycin Renal failure: reduce klacid (other 2 no change) 1 to 2 hrs 3 to 4 hrs 2- 3 days 500mg q6h 500mg bd 500mg qd x 3/7 Interfere clearance of other dugns e.g. theophyllin, carbamazipine increased their plasma level e.g. COAD on theophyllin use azithromycin better if need to use macrolide

Cockcroft formula (CrCl estimation) CrCl (male) = [1.24 x wt (kg) x (140-age)]/ serum Cr (umol/L); CrCl (female) = 0.85 x CrCl (male) 1. For meningitis Most common 4: Strep pneumonia, H influenzae, Montellia, Listeria Penicillin is for covering listeria monocytogenes infection not needed in every patient, only in 3 cases: a. neonate, b. elderly, c. immunocompromised Good penetration Cephalosporins: Cefotaxime (Claforan), Ceftriazone (Rocephin), Ceftazidime (Fortum), Cefepime (Maxipime) 2. If suspect strep pneumonia Empirically start vancomycin if severe infection As mostly resistant to all peniciilin and cephalosporin If C/ST came back to be sensitive, stop vancomycin 3. Pyelonephritis Aminoglycoside has high renal cortex concentration good for treatment If fever not decreased when using B-lactam or rocephin, may aminoglycoside can see RFT gradually improved i.

Tetracyclines
Tetracycline, oxytetracycline, doxycycline, minocycline, demeclocycline Broad spectrum BUT widespread resistance. Intracellular organisms e.g. Chlamydiae (psittacosis, trachoma), Rickettsiea (Q fever), Brucellae (with streptomycin or rifamipicin), Spirochaetes (Borrelia burgdorferiLyme disease)/ acne/ SIADN Avoid in MG/ SLE NOT to take with milk/ Zince, Irone, Mg, aluminium

Other antibiotics for mutiresistant organisms

Linezolid (oxazolidinone antibiotics, reversible MOI): MRSA, Vancomycin-resistant enterococci Quinupristin with dalfopristin (Mixture of strephtogramin antibiotics) for MRSA (NOT for Enterococcus faecalis/ G-ve organims)

Anaerobes Naturally resistant to certain abx e.g. aminoglycosides and fluoroquinolone Anaerobic G (=) non=sporeforming rods susceptible to B-lactam, NOT metronidazole Anaerobic G (-) bacilli are usually B-lactamase produces B-lactam/ B-lactamase inhibitors MSSA Penicilin-resistant SA - Penicillinase (B-lactamase) production S aureus bacteremia if no obvious source, must treat and order echocardiogram as 2-41% associated with infective endocarditis No penicillin allergy Minor allergy Life threatening allergy MRSA Cloxacillin Cefazolin IV/ cephalothin oral Vancomycin/ Linezolid

Metronidazole (Flagyl) Clindamycin B-lactam/ B-lactamase inhibitors Carbapenem Chloramphenicol Cloxacillin B-lactamase inhibitor Cephalosporin 1>2/3 Carbapenems no need to add cloxacillin unless bacteremia or endocarditis Macrolides Clindamycin FQ Glycopeptides Rifampicin Murpirocin

PBP2a with low affinity of B-lactam abx Resistant to all B+lactam (including carbapenem) Need glycopeptides, linezolide, quinupristin-dalfopristin Colonization e.g. superficial wound, bedsore No tx Invasive/ severe infection e.g. bacteremia Uncomplicated UTI Imipene or meropenem Augmentin, FQ, aminoglycoside, nitrofurantoin, cotrimoxazole

Vancomycin Linezolid (Zyvox)

ESBL

B-lactam/B lactamases inhibitors FQ, aminoglycosides Tazocin; Timentin; imipenem/meropenem Tazocin, Timentin Fortum, Sulperazon, Maxipime Imipenem, meropenem FQ: levo/ cipro Aminoglycoside: amikacin, gentamic, tobramycin (best)

Anti PA

Thrives in moist environment e.g. soil and water Human colonization within GI tract Underlying disease: cystic fibrosis/ bronchiectasis, hematological malignancy, burns, mechanical ventilation