PROTEIN SYNTHESIS INHIBITORS THEY WORK BY TARGETING BACTERIAL RIBOSOMES AMINOGLYCOSIDES MACROLIDES TETRACYCLINES SPECTINOMYCIN

AMINOGLYCOSIDES GENTAMICIN TOBRAMYCIN AMIKACIN STREPTOMYCIN MOA: INHIBIT PROTEIN SYNTHESIS BY BINDING TO 30S RIBOSOMAL SUBUNIT CONCENTRATION DEPENDENT KILLERS

AMGS MOA CROSS THE OUTER MEMBRANE TO PERIPLASMIC SPACE THROUGH PORIN PROTEINS ACTIVELY TRANSPORTED ACROSS THE CELL MEMBRANE BY AN OXYGEN- DEPENDENT PROCESS IRREVERSIBLY BIND TO THE 30S RIBOSOMAL SUBUNIT LEADING TO MISREADING OF THE GENETIC CODE AND INHIBITION OF PROTEIN SYNTHESIS. PHARMACOKINETICS PENETRATE MOST BODY FLUIDS WELL, EXCEPT FOR THE CSF. HIGH CONCENTRATION OF AMG ACCUMULATE IN THE RENAL CORTEX AND INNER EAR NEPHROTOXCITY: DIRECTLY RELATED PLASMA LEVELS AND DURATION OF TREATMENT OTOTOXICITY: SEVERE ACUTE TUBULAR NECROSIS MAY OCCUR

AMINOGLYCOSIDES-PHARMACODYNAMIC SE: RENAL DYSFUNCTION: 5-25% MONITOR BUN / S.CR AND ADJUST DOSE MONITOR TROUGH LEVELS FOR TOXICITY GOAL TROUGH: < 1 MG / DL FOR ONCE DAILY DOSING NEUROMUSCULAR BLOCK: RARE, ASSOCIATED WITH RAPID IV INFUSION EXTENDED INTERVAL DOSING : LESS NEPHROTOXICITY POST ANTIBIOTIC EFFECT AGAINST GRAM -

AMINOGLYCOSIDES AGENTS GENTAMICIN TOBRAMYCIN AMIKACIN NETILMICIN STREPTOMYCIN PRIMARY COVERAGE: GRAM - !!!!!!!! INCLUDING PSEUDOMONAS VERY LITTLE GRAM + SYNERGY FOR ENDOCARDITIS STAPH, ENTEROCOCCUS

MACROLIDES BACTERIOSTATIC IN GENERAL BACTERIOCIDAL AGAINST STREPTOCOCCI-TIME DEPENDENT ERYTHROMYCIN CLARITHROMYCIN AZITHROMYCIN

MACROLIDES AGENTS ERYTHROMYCIN CLARITHROMYCIN AZITHROMYCIN PRIMARY COVERAGE ATYPICALS!!! CHLAMYDIA LEGIONELLA MYCOPLASMA MODERATE GRAM + MODERATE GRAM -

MACROLIDES MOA: INHIBIT BACTERIAL PROTEIN SYNTHESIS  BIND TO 50S RIBOSOMAL SUBUNIT ERYTHROMYCIN:  MORE SE’S ( ESPECIALLY GI )  MORE DI’S ( CYP1A2, CYP3A4 INHIBITOR ) AZITHRO / CLARITHRO BETTER TOLERATED  LESS SE’S, QD - BID DOSING CLARITHROMYCIN NEEDS RENAL ADJUSTMENT AT CRCL <30 ML/MIN AZITHROMYCIN HAS VERY FEW CLINICALLY SIGNIFICANT DRUG INTERACTIONS INDICATION: SKIN AND SOFT TISSUE INFECTIONS

MACROLIDE SIDE EFFECTS Side EffectErythroClarithro/Azithro GI upset25-30%5-10% Rash5%Rare  LFTs2-5%Rare Transient hearing loss Rare

KETOLIDES: TELITHROMYCIN (KETEK) STRUCTURALLY RELATED TO MACROLIDES MOA: SAME AS MACROLIDES, BUT HAS ACTIVITY AGAINST RESISTANT STRAINS CONC DEPENDENT, BACTERICIDAL PO FORMULATION FDA INDICATION:  COMMUNITY-ACQUIRED PNEUMONIA Lacks portion of macrolide structure = less resistance

TELITHROMYCIN (KETEK) ADVERSE EFFECTS VISION PROBLEMS: 3% BLURRED VISION ACCOMODATION ISSUES DIARRHEA: 11% NAUSEA: 8% HEADACHE: 6% DIZZINESS: 4% PREGNANCY CATEGORY C ACTIVITY STREPTOCOCCUS SPP. STAPHYLOCOCCUS AUREUS NOT MRSA H. INFLUENZAE MORAXELLA CHLAMYDIA MYCOPLASMA LEGIONELLA Requires renal and hepatic dosing adjustment!

TETRACYCLINES DOXYCYCLINE, TETRACYCLINE, MINOCYCLINE

MOA: BIND TO 30S RIBOSOMAL SUBUNIT TO INHIBIT BACTERIAL PROTEIN SYNTHESIS NOT USED AS MUCH ANYMORE: OTHER OPTIONS AVAILABLE COVERAGE: GRAM +: STAPH (NOT MRSA), STREP GRAM -: MORAXELLA, H. FLU, E. COLI ANAEROBES: B. FRAG, C. DIFFICILE ATYPICALS: CHLAMYDIA, LEGIONELLA, MYCOPLASMA DOXYCYCLINE USED FOR OUTPATIENT TX. OF CAP ALL CAN BE USED TO TREAT ACNE

TRIMETHOPRIM-SULFAMETHOXAZOLE (BACTRIM, COTRIM, SEPTRA)

MOA: EACH INHIBITS A STEP IN BACTERIAL FOLIC ACID SYNTHESIS NO FOLIC ACID  BACTERIAL CELL DEATH (BACTERICIDAL) HIGH URINARY CONCENTRATIONS PRIMARY USE CURRENTLY: UTI HIV PROPHYLAXIS OF OPPORTUNISTIC INFECTIONS PRIMARY COVERAGE: STREP PNEUMO  PROTEUS H. FLU  ENTEROBACTER E. COLI COMMUNITY ACQUIRED MRSA (METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS)

TRIMETHOPRIM-SULFAMETHOXAZOLE SIDE EFFECTS N/V ( >10%) DIARRHEA (>10%) RASH (>10%) FEVER (>10%) LEUKOPENIA/THROMBOCYTOPENIA STEVENS-JOHNSON SYNDROME (1-10% ) DRUG INTERACTIONS BACTRIM MAY DISPLACE OTHER HIGHLY PROTEIN BOUND DRUGS WARFARIN PHENYTOIN METHOTREXATE CONTRAINDICATIONS: PREGNANCY (3RD TRIMESTER ONLY) SEVERE LIVER DISEASE

CLINDAMYCIN & METRONIDAZOLE CLINDAMYCIN MOA: INHIBITS BACT. PROTEIN SYNTHESIS SIDE EFFECTS: GI!!!!! 25-30% #1 ABX CAUSING C.DIFF COLITIS/ # TREATED  LFTS: RARE RASH: 2-5% DIS MAY ENHANCE NEUROMUSCULAR BLOCKADE OF SUCH AGENTS ALSO ACTIVE AGAINST: STREP, MSSA METRONIDAZOLE MOA: DAMAGE BACTERIAL DNA  BACTERIOCIDAL SIDE EFFECTS: GI: 5-10% SEIZURES 2-5% PANCREATITIS: RARE DARK URINE: HIGH INCIDENCE DIS ETOH: DISULFIRAM-LIKE REACTION INHIBITS WARFARIN METABOLISM  INR ONLY REQUIRES RENAL DOSING IF CLCR <10 ML/MIN Grouped together because they are potent at treating ANAEROBES