Pharm E1: ID & misc agents

Staphylococci

Staphylococci

G+: S. Aureus → MSSA or MRSA; G-: Staph epidermis

Streptococci

S. pneumoniae

Enterococci

Entero. faecalis, Entero faecium

Cocci

Petopstreptococcus, Peptococcus

Bacilli

C. diff, C. perfringens

Enterobacteriaceae

Escherichia, Klebsiella, Salmonella, Shigella

Anaerobes

Bacteroides fragilis

Atypical Pathogens

Chlamydia trach, chlamydia pneumonie, legionella pneumoniae, mycoplasma pneumoniae

Infectious agents of Skin/soft tissue

S. Aureus, Staph epidermis, Strep progenies, Pasteurella

infectious agents Bone and Joint

S. Aureus, Staph epidermis, Streptococcus, Neisseria gonorrheae, G- rods

infective agents for meningitis

S. pneumoniae, Neisseria mentngitidis, H. influenzae, Group B Streptococcus, Listeria, E. coli

infective agents of the abdomen

E. coli, proteus, Klebsiella, enterococcus, bacteroides

Infective agents of the urinary tract

E. coli, proteus, Klebsiella, enterococcus, staph saprophyticus

Infective agents of the mouth

Peptococcus, Peptostreptococcus, Actinomyces

Infective agents of the upper respiratory tract

S. pneumoniae, H. influenza, Moraxella catarrhalis, Streptococcus progenies (Group A)

Infective agents of the lower respiratory tract (community)

S. pneumonia, H. influenza, K pneumonia, Legionella, mycoplasma pneumoniae, Chlamydia penumoniae

Infective agents of the lower respiratory tract (nosocomial)

MRSA, P. aeruginose, enterobacteria, K. pneumonia, serratia

Resistant gram (+) bacteria

MRSA, VRE, VRSA

resistant gram (-) bacteria

ESBL, KPC’s, Klebsiella, escherichia, P aeruginosa, acintobactero

What causes bacterial resistance?

indiscriminate antimicrobial use, >7 days on ventilation, prolonged hospital stay, prior antibiotic use

What do you need to consider when choosing an antibiotic?

spectrum of activity, pharmacokinetics, pharmacodynamics, toxicities

Bactericidal

disrupts bacterial function so much that death will occur

Which antibiotics are bactericidal?

penicillins, cephalosporins, aminoglycosides, vancomycin, fluoroquinolones, metronidazole

Bacteriostatic

inhibits a vital pathway used in the growth of the bacteria, but does not directly cause death

What antibiotics are bacteriostatic?

erythromycin, tetracyclines, sulfonamides, trimethoprim, clindamycin

What is a concentration-dependent drug?

higher the drug concentration, the greater the killing

What is time-dependent?

killing extent remains stable at a particular drug concentration

Which type of antibiotic has the post-antibiotic effect?

concentration-dependent

Which type of antibiotic is best to give in continuous or frequent infusions?

time-dependent

Which drugs are B-lactam antibiotics?

penicillins, cephalosporins, carbapenems, monobactams

What drugs are B-lactamase inhibitors?

clavulanic acid, sulbactam, tazobactam

What are other antibiotics?

bacitracin, vancomycin, daptomycin

What are 1st gen cephalosporins?

cefadroxil, cefazolin, cephalexin

What are 2nd gen cephalosporins?

celadon, cefprozil, cefuroxime, cefoxitin

What are 3rd gen cephalosporins?

cefdinir, cefixime, cefotaxime, ceftrazidime, ceftibuten, cetizomine, ceftriazone

What are 4th gen cephalosporins?

cefepime

What is the MOA of Penicillin?

cross-linking enzyme (PBP) accidentally bind to penicillin → inactivates enzyme preventing new cross links → disrupts cell wall

Natural Penicillins: Pen G

Coverage: G+ (no staph coverage), anaerobic activity (-bacteroides), no activity against aerobic G-

Monitoring: signs and symptoms of anaphylaxis

Aminopenicillins: Amoxicillin

Coverage: G+ (no staph coverage), anaerobic activity (-Bacteroides), some Gram - aerobes

Drug of choice: Enterococcus, Listeria, endocarditis prophylaxis, URTI, CAP

Rxn: anticoags → prolonged PT, dec effectiveness of oral contraceptives

Aminopenicillins: side effects

• hepatic dysfunction, hepatitis, jaundice

• C. diff infection

• SJS, TEN

• interstitial nephritis, hematuria, crystalluria

• anemia, thrombocytopenia

Penicillin: adverse reactions

• hypersensitivity rxn

• rash

• diarrhea

• NEED to monitor renal and hepatic function & platelets

B-lactamase Inhibitors

chemicals w/ no antibacterial activity that irreversibly inactivate B-lactamase

(sulbactam, tazobactam, clavulanate)

Aminopenicllin’s + B-lactamase Inhibitors

Increase anaerobe coverage and covers MSSA

Drug of choice: skin/soft tissue, diabetic foot, animal/human bites

(Augmentin: amox/calv)(Unasyn: amp/sulbact)

Penicillin-Resistant Penicillins (anti-staph pen)

Designed solely to cover S. Aureus (MSSA) (nafcillin, oxacillin, dicloxacillin)

Monitor: hepatic function & CBC, s/sx of anaphylaxis

What is the drug of choice for MRSA?

Vancomycin

Antipseudomonal Penicillins

Broad spectrum, Maintains G+ coverage (MSSA only), added G-

Piperacillin, Piper-tazobactam (Zosyn)

Drug of choice: polymicrobial, nosocomial, pseudomonal, intra-abdominal infections

Antipseudomonal Penicillins: adverse reactions

• Hypersensitivity

• Rash

• Diarrhea

• Monitor: S/sx analyphalxis, renal function, CBC -bleeding

Cephalosporins

• good cerebrospinal fluid penetration

• Penicillin cross-sensitivity

• spectra of activity

• anti-pseudomonas activity

• mostly renal elimination

Cephalosporins: side effects

• s/sx of allergic rxn

• nausea/vomiting/diarrhea

• CBC

1st Gen Cephalosporins

• great G+ activity (no enterococcus)

• some G- (E. coli, Protues, Klebsiella)

• Cefazolin: surgical prophylaxis (IV)

• Cephalexin: skin & soft tissue/cellulitis, & UTI (PO)

2nd Gen Cephalosporin

• often used for UTIs, URIs, surgical phrophylaxis

• more G- activity than 1st gen (H. influenza, Enterobacter, Proteus, Neisseria, E. coli, Klebsiella)

• Cefotetan & Cefoxitin (IV)

• Cefuroxime (PO/IV)

• Cefprozil (PO)

3rd gen Ceph

• loses some G+, even better G- coverage

• extra coverage against Serratia & M. catarrhalis

• Ceftrizone, Ceftazidime, Cefotaxime, (IV)

• Cefdinir, ceefixime (PO)

4th gen Cephalosporins

• Cefepime: broad spectrum Antibiotic

  • G- coverage, anti-pseudomonal activity, G+ coverage, no MRSA or Enterococcus, no anaerobic activity

• Drug of choice

  • neutropenic fever, nosocomial infections, pseudomonas infections

5th Gen Cephalosporins: Ceftaroline

• Uses

  • G- coverage, G+ (no enterococcus)

  • MRSA coverage

  • non anaerobic activity

• FDA approved indications

  • community acquired penumonia

  • skin/soft tissue infections

• must be renally adjusted

5th Gen Cephalosporins: Ceftolozane/tazobactam

• Uses

  • G-, G+ (no MRSA or enterococcus)

  • anti-pseudomonal activity

  • some anaerobic activity

• FDA approved indications

  • complicated intra-abdominal infections

  • complicated UTIs

Monobactam

• only G-, activity against P. aeruginosa, enterobact activity

• monitor liver function, diarrhea, S/sx of anaphylaxis

• NO cross-reactivity with B-lactams

Carbapenems

• very broad spectrum w/ G+, G-, anaerobic coverage

• more resistant to hydrolysis from B-lactamases

• uses: nosocomial infection, meningitis, MDR G- infxn, extended B-lactamse spectrum

• monitor: renal/hepatic fxn, CBC, anaphylaxis, seizures

• -penem

Vancomycin

• Glycopeptide antibiotic

• targets cell well -blocks cross linking, more difficult to develop resistance

• G+ ONLY, generally IV

• Uses: MRSA, PCN allergic infections, C. diff, endocarditis, osteomyelitis, surgical prophylaxis

• Monitor: red man syndrome, phlebitis, fever, chills

How do Protein Synthesis Inhibitors work?

• target the bacterial ribosome

  • bacterial : 70s (50s/30s)

  • mammalian : 80s (60s/40s)

• 50s: macrolides, clinda, chloramphenicol, streptogramins

• 30s: aminoglycosides, tetracylines

Macrolides

• MOA: bind 50s and inhibit proteins synthesis by blocking transpeptidation

• Erythromycin, clarithromycin, azithromycin

• Coverage: G+, G-, not used for anaerobes, atypicals (legionella, mycoplams pneumo, chlamydophila pneumo, chlamydia trach)

• Uses: RTI, skin infxn, MAC, chlyamida tach, H. pylori

• can cause hearing loss and QT prolongation (Torsades de pointes)

• interacts w/ CYP3A

Tetracycline

• MOA: binds to 30s, bind 16s rRNA preventing tRNA, bacteriostatic, broad spectrum

• tetra, mino, doxy

• coverage: excellent- atypicals, animal borne organisms; good - GPs, enterococcus, MRSA, common Gns, anaerobes, H. pylori; poor- pseudomonas, C. diff

• Adverse Rxn: photosensitivity, discoloration of teeth

Glycylcyline (Tigecycline)

• MOA: binds to 30s, bacteriostatic

• uses: complicated skin infxn, complicated intra-abdominal infxn

• uses loading doses (IV)

• adverse: vomit, nausea, diarrhea, fever

Aminoglycosides

• G- ONLY, covers enterococcus

• Uses: febrile neutropenia, sepsis, enterococcal synergy

• watch: renal toxicity, ototoxic, renally adjusted

• Amikacin, Gentamicin, Tobramycin

• monitro peak/trough for administration

Oxazolinodinone

• resistant G+ (MDR pneumo, MRSA, VRE), no G- or anaerobes

• Linezolid (50s), Deptomycin (bactericidal, inhibits DNA, RNA, protein synthesis)

• Uses: HAP-MRSA, CA-MRSA

• toxicity → thrombocytopenia, SSRI interactions → serotonin synd

Fluoroquinolones

• dual MOA: inhibit bacterial DNA Gyrase, inhibition of bacterial topoisomerase IV

• Uses: CAP, sinusits, UTI, infectious diarrhea, osteomyelitis

• Interaction: iron, antiacids, QT interval, CNS, warfarin, dairy

• OVERUSE= resistance, collateral dammage, C. diff

• levofloxacin, ciprofloxacin, moxifloxacin

• Side effects: CYP450, QT prolong, tendonitis, peripheral neuropathies

2nd gen Fluoroquinolone

• Ciprofloxacin

• G- & atypical coverage; ± pseudomonas coverage

• Watch renal function

3rd gen Fluoroquinolone

• Levofloxacin: watch renal; + pseudomonas coverage

• Moxifloxacin: NOT for UTI; - pseudomonas coverage

• G-; more G+

• Uses: CAP, strep PNA, atypical coverage

Clindamycin

• G+, anaerobes, no G-, covers MRSA

• Uses: toxin-mediated disease, osteomyelitis, surgical prophylaxis (PCN allergy), intra-abdominal combination, skin/soft tissue

• Side Effects: rash, neutropenia, thrombocytopenia, C. diff, colitis

Sulfamethoxazole and Trimethoprim (Sulfa, Bactrim)

• MOA: inhibits PABA → DHF; inhibits DHF → THF

• G+, G-, MRSA, pneumo carinii, nocardia, toxoplasma gondii

• Uses: PJP treatment and prophylaxis, UTI, bacterial prostatitis, orchitis, epididymitis, RTI, GI infection

• Adverse: GI, can inc INR w/ warfarin, rash, SJS,TEN, hepatic, blood dyscrasias

Metronidazole (Flagyl)

• MOA: interacts w/ bacterial DNA → helical structure loss and strand breakage

• G± anaerobes, parasites

• Uses: C. diff, intra-abdominal combination, STI

• Side effects: HA, nausea/vomiting, disulfiram-like rxn w/ ethanol

Polymixin B & Polymixin E

• MOA: displaces Mg2+ & Ca2+ → disrupts membrane

• Broad G-

• resistance not common

• BLACK BOX: toxicity of nephro & neuro, neruomusclar blockade

Antifungal drugs

Polyenes, Flucytosine, Imidazoles, Triazoles, Echinocadins, Griseofulvin, Allymamines

Polyenes

MOA: effect cell membrane -alter membrane integrity and permeabilityand inhibit ergosterol synthesis

Drugs: Amphotericin B, Nystatin, Natamycin

Azoles

MOA: effect cell membrane -inhibit lanosterol demethylases (dec ergosterol)

Allyamines

MOA: effect cell membrane -inhibit squalene epoxidase (dec ergosterol)

Drugs: Naftifine, terbinafine

Echinocandins

MOA: effect cell wall - inhibit D-glucans in cell wall formation

Drugs: caspofungin, micafungin, anidulafungin

Griseofulvin

MOA: effect cell division -inhibits microtubules

Flucytosine

MOA: effects nucleic acid synthesis - converted to 5-Fluroracil then to 5-Fluorouradin → inhibits thymidylate synthase → inhibits DNA synthesis

Amphotericin B

• MOA: (polyene) forms channels in ergosterol membranes to allow K+ & Mg+ to leak out of cell → oxidative damage to membranes

• Uses: cryptococcus, blastomyces, histoplasma, candida, coccidioides, aspergillus

• Adverse: fever/chills, pretreat w/ acetaminophen, antihistamines, corticosteroids

5-Flurocytosine

• MOA: inhibits DNA and RNA synthesis

• Uses: cryptococcus neoformans, candida, w/ amph B for crypto meningitis

• Adverse: bone marrow suppression, hepatotoxicity, GI disturbances, rash

Imidazoles & Triazoles

• MOA: inhibits fungal CYP450 involved in conversion of lanosterol to ergosterol

• Uses: candida, cryptococcus, blastomyces, histoplasma, coccidoides, aspergillus, worms (tinea)

• ketoconazole. itraconazole, posaconazole, fluconazole, voriconazole

Echinocandins

• caspofungin, micafungin, anidulafungin

• MOA: inhibit cell wall formation

• Uses: esophageal candidias, systemic aspergillus, febrile patients -all when not responding to 1st line tx

• adverse: tachy, HA, insomnia, hypo K & Mg, blood dycrasias

Griseofulvin

• MOA: interrupts mitotic spindles, stops cell division in Dermatophytes; derived from PCN geriseofulvum

• Uses: effective against numerous dermatophytes, but not candida

• Adverse: HA, confusion, fatigue, blurred vision

Tolnafate

• MOA: inhibits ergosterol synthesis by inhbiting squalene epoxidase → distorts hyphae & stunts mycelial growth

• Uses: cutaneous mycoses, worms (tinea) - tinea unguium

Benzimidazoles (anthelminthics)

• MOA: inhibits formation of helminth microtubules, block glucose uptake → parasite death

• Use: hookworms, roundworms, pinworms, whipworms

• Adverse: GI upset, hypersensitivity, rash

Pyrantel pamoate (anthelminthic)

• releases acetylcholine and inhibits cholinesterase acting as a depolarizing neuromuscular blocker → paralysis and death

• Uses: pinworm, hookworm

• Adverse: dizziness, HA, GI upset