Microbiology Flashcards
Tetracyclines
tetracycline, doxycyclne, minocycline
MOA: bacteriostatic
Bind to 30s and prevent attachment of aminoacyl-tRNA-limited CNS penetration
Doxycycline can be used in renal failure (fecal elimination)
Do not take with milk, antacids, or iron containing preparations due to divalent cations (Ca and Mg) inhibit absorption in gut
Clinical: Borrelia burgdorferi, M. pneumoniae, Rickettsia and Chlamydia
Acne
Toxicity: GI distress, discoloration of teeth and inhibition of bone growth in children, photosensitivity-sun burns
Contraindicated in pregnancy
resistance: decrease uptake or increase efflux out of bacterial cells by plasmid encoded transport pumps
3rd gen cephalosporins
Ceftriaxone, cefotoxamine, ceftazindime
MOA: Inhibit cell wall synthesis but less susceptible to penicillinases
Bacterocidal
Irreversibly binds to penicillin binding proteins (transpeptidases)
Clinical: serious gram- infections
Cetriaxone-meningitis and gonorrhea
Ceftazidime-Pseudomonas
Toxicity: hypersentivity reactions, vitamin K deficiency, low cross reactivity with penicillins
Increase nephrotoxicity of aminoglycosides
Resistance: change in protein structure in penicillin binding proteins
Macrolides
Azithromycin clarithromycin, erythromycin
MOA: inhibit protein synthesis by blocking translocation
Bind to 23S rRNA of the 50s ribosomal subunit
Bacteriostatic
Clinical: Atypical pneumonias, STDS-chlamydia, and gram psotiive cocci-allergtic to penicillin
Toxicity: GI motility issues, arrhytmia caused by prolonged QT, acute Cholestatic hepatitis, Rash, Eosinophilia,
Increases serum concentration of theophyllines, oral anticoagulants
Resistance: Methylation of 23S rRNA-binding site prevents binding of drug
4th gen Cephalosporins
Cefepime
MOA: Inhibit cell wall synthesis but less susceptible to penicillinases
Bacterocidal
Irreversibly binds to penicillin binding proteins (transpeptidases)
Clinical: increased activity against pseudomonas and gram+ organisms
Toxicity: hypersentivity reactions, vitamin K deficiency, low cross reactivity with penicillins
Increase nephrotoxicity of aminoglycosides
Resistance: change in protein structure in penicillin binding proteins
Oxacillin, nafcillin, dicloxacillin
MOA: bind penicillin binding proteins (transpetptidases)-catalyze cross linking of peptidoglycan cell wall formation specifically joining of amino acids with terminal D-alanine-D-alanine therefore structural analog of D-alanine-D-alanine
Activates autolytic enzymes by weakening cell wall
Clinical: S. aureus-except MRSA due to altered penicillin-binding proteins target site
Penicillnase resistant because bulky R group blocks access of B-lactamase to B-lactam ring
Toxicity: hypersensitivity reactions, interstitial nephritis
Vancomycin
MOA: inhibits cell wall peptiodglycan formation by binding D-ala D-ala portion of cell wall precursors
Bacterocidal
Clinical: gram+ only-major resistant organisms (MRSA, enterococci, and Clostridum difficile)
Toxicity: well tolerated in trouble
Nephrotoxicity, Ototoxicity, Thrombophlebitis, diffuse flusing (prevent with antihistamines and slow infusion rate)
resistance: Bacteria have amino acid modification of D-ala Dla to D-ala D-lac
Toxicity:
Ticarcillin, piperacillin
MOA: bind penicillin binding proteins (transpetptidases)-catalyze cross linking of peptidoglycan cell wall formation specifically joining of amino acids with terminal D-alanine-D-alanine therefore structural analog of D-alanine-D-alanine
Activates autolytic enzymes by weakening cell wall
Clinical: Pseudomonas and gram - rods
Susceptible to penicillinase-use with B-lactamase inhibitors
Toxicity: hypersensitivity reactions
B-lactamase inhibitors
Clavulanic acid, Sulbacam, Tazobactam
Added to penicillin antibiotics to protect the antibiotic from destruction by B-lactamase
Aminoglycosides
Gentamicin, Neomycin, Amicacin, Tobramycin, Streptomycin
MOA: Bactericidal
Inhibit formation of initiation (bind 30s ribosomal subunit and distorts structure blocking INITIATION) complex and cause misreading of mRNA
Block translocation
Require O2 for uptake; ineffective against anaerobes
Clinical: Severe gram-rod infections
Synergggistic with B-lactams
Neomycin for bowel surgery
Toxicity: Nephrotoxicity (especially with cephalopsporins), Neuromuscular blockade, ototoxicity (especially with loop diuretics), teratogen
Resistance: baceriaal transferase enzymes inactivate the drug by acetylation, phosphorylation or adenylation
2nd gen cephalsporins
Cefoxitin, cefaclor, cefuroxime
MOA: Inhibit cell wall synthesis but less susceptible to penicillinases
Bacterocidal
Irreversibly binds to penicillin binding proteins (transpeptidases)
Clinical: gram + cocci, Heamophilus influenza, enterobacteri aerogenes, Neisseria, proteus, E. coli, Kelbseilla, serratia
Toxicity: hypersentivity reactions, vitamin K deficiency, low cross reactivity with penicillins
Increase nephrotoxicity of aminoglycosides
Resistance: change in protein structure in penicillin binding proteins
5th gen Cephalosporins
Ceftaroline
MOA: Inhibit cell wall synthesis but less susceptible to penicillinases
Bacterocidal
Irreversibly binds to penicillin binding proteins (transpeptidases)
Toxicity: hypersentivity reactions, vitamin K deficiency, low cross reactivity with penicillins
Increase nephrotoxicity of aminoglycosides
Clinical: broad gram+ and gram-organism coverage including MRSA
DOES NOT cover pseudomonas
Resistance: change in protein structure in penicillin binding proteins
Ampicillin, amoxicillin
MOA: bind penicillin binding proteins (transpetptidases)-catalyze cross linking of peptidoglycan cell wall formation specifically joining of amino acids with terminal D-alanine-D-alanine therefore structural analog of D-alanine-D-alanine
Activates autolytic enzymes by weakening cell wall
Wider spectrum than penicillin especially with clavulonic acid
Amoxicillin better oral bioavailiability
Clinical: haemophilus, E. coli, Listeria, proteus, Salmonella, Shigella, H. pylori (amoxicillin)
Toxicity: hypersensitivity reactions, rash, pseudomembranous colitis
Resistance: penicillinase in bacteria cleaves B-lactam ring
H2O2
MOA: Destructive free radical production
Oxidize cellular components
IS sporicidal
Used for inanimate objects
Skin cleansing and wound debridement
Aztreonam
MOA: monobactam resistant to B-lactamases
Prevents peptidoglycan cross-linking by binding to penicillin binding protein 3
Syngergistic with aminoglycosides
no cross-allergencity with penicillins
Clinical: gram- rods only
For penicillin allergic patients and those with renal insufficiency who cannot tolerate aminoglycosides
Toxicity: usually non-toxic ocasional GI upset
Carbapenems
Imipenem, meropenem, ertapenem, doripenem
MOA: imipenem is broad spectrum-B-lactamase resistant
Always admistered with cilistatin (inhibitor or renal dehydropepetdase I) which decreases inactivation of drug in renal tubules
Clinical: gram+ cocci, gram - rods and anaerobes
wide specrum
Side effects limit to to life threatening infections where other drugs have failed
Toxicity: GI distress, skin rash and seizures (meropenem less)
Penicillin G (IV), V (oral)
MOA: bind penicillin binding proteins (transpetptidases)-catalyze cross linking of peptidoglycan cell wall formation specifically joining of amino acids with terminal D-alanine-D-alanine therefore structural analog of D-alanine-D-alanine
Activates autolytic enzymes by weakening cell wall
Clinical: gram + organisms, N. meningtidis, and T. pallidum
Toxicity: hypersensitivity, hemolytic anemia
Resistance: Penicillinase in bacteria cleaves B-lactam ring
Alcohol (Disinfectant)
MOA: disrupts cell membranes and denatures proteins
Not sporicidal
Disorganizes lipid membranes making them leaky
Denatures cell proteins
Requires water
Chlrohexidine
MOA: disrupts cell membranes
Coagulation of cytoplasm
Not sporicidal
Antiseptic of choice for surgical and percutaneous procedures
CI: neurologic, ototoxic, and opthalamologic procedures due to neurotoxicity
Iodine
MOA: halogenation of proteins and nucleic acids
IS sporicidal
More skin irritation and toxicity than others
Less effective than chlorohexidine-alcohol combo
Formaldehyde and glutaraldehyde
MOA: alkylating and cross linking DNA and proteins
Used for sterilization of hospital instruments that cannot withstand autoclaves
Clindamycin
MOA: blocks peptide transfer at 50S ribsomal subunit
Bacteriostatic
Clinical: Anaerobic infections in aspiration pneumonia, lung abscesses, and oral infections
Effective against invasive Group A Strep. infection
Toxicity: psedomembranous colitis (C. difficile overgrowth), fever diarrhea
Treats anaerobes above the diaphragm
Chloramphenicol
MOA: blocks peptidyltransferase at 50s ribosomal subunit
Bacteriostatic
Clinical: Meningtis (H. influenzae, N. meningitidis, Strep. pneumo) and Rocky Mountain spotted fever (Rickettsia rickettsii)
Toxicity: anemia, apalstic anemia, gray baby syndrome (premature infants lack liver UDP-glucoronyl transferase)
Reversible cytopenia
Irreversible pancytopenia (without Bone marrow transplantation)
Resistance: plasmid encoded acetyltransferase inactivates the drug
Sulfonamides
Sulfamethoxazole, sulfisoxazole, sulfadiazine
MOA: inhibit folate synthesis
para-aminobenzoic acid (PABA) antimetabolites inhibit dihydropteroate synthase
Bacteriostatic
Clinical: gram+, gram-, Nocardia, Chlamydia, simple UTI
Toxicity: hypersensitivity raections, hemolysis if G6PD deficient, nephrotoxicity, photosensitivity, kernicterus in infants, displace other drugs from albumin
Resistance: altered enzyme (bacterial dihydropteroate synthase), decrease uptake, or increase PABA synthesis
Trimethoprim
MOA: inhibits bacterial dihydrofolate reductase
Clinical: used in combo with sulfonamides
Causes sequential blockade of folate synthesis
Combo used for UTIs, Shigella, Salmonella, Pneumocystis jirovecii, pneumonia treatment and prophylaxis
Toxicity: megaloblastic anemia, leukopenia, granulocytopenia
Fluoroquinolones
Ciprofloxacin, norfloxacin, levofloxacin, ofloxacin, sparfoxacin, moxifloxacin, gemifloxacin, enoxacin, Naldixic acid (quinolone)
MOA: Inhibit DNA gyrase (topoisomerase II)
Bacterocidal
Clinical: gram negative rods of urinary and GI tracts (Psudomonas), Niesseria, some gram positive organisms
Toxicity: GI upset, superinfections, skin rashes, headache, dizziness
Can cause tendonitis, tendon rupture (>60 or taking prednisone), leg cramps and myalgias
CI in preganncy, nursing mothers and children under 18 due to cartilage damage
Some prolong QT
Resistance: Chromosome-encoded mutation in DNA gyrase, plasmid mediated resistance, efflux pumps
Do not take with antacids
Metronidazole
MOA: forms free radical toxic metabolites in bacterial cell that damage DNA
Bacterocidal and antiprotozoal
Clinical: Giardia, Entamoeba, Trichomonas, Gardenerlla vaginalis, Anaerobes (below diaphragm)
Use with proton pump inhibits and clarythromycin against H. Pylori
Toxicity: Disulfuram-like reaction (sever flushing, tachycardia, hypotension) with alcohol, headache, metallic taste
Increase acetyladelhyde
Isoniazid
MOA: decreases synthesis of mycolic acids
Bacterial catalase-peroxidase (encoded by KatG) needed to convert INH to active metabolite
Bacteria cannot make cell wall or multiply and lose acid-fastness
Clinical: Mycobacterium tuberculosis
Solo prophylaxis against TB
Toxicity: neurotoxicity (peripheral neuropathy-use pyridoxine-B6), hepatotoxicity, lupus
Resistance:
- decrease in bacterial expresssion of catalase-peroxidase enzyme required for activation
- modifaction of protein target binding site
Can compete with B6 in the synthesis of NTs leading to defective end products
Increase urinary excretion of B6 leading to deficiency
Rifamycins
Rifampin, rifabutin
MOA: Inhibits DNA dependent RNA polymerase
Clinical: Mycobacterium tuberculosis
delays resistance to dapsone when used for leprosy
Used for meingoccal prophylaxis and chemoprophylaxis in children with H. influenza
Toxicity: Hepatotoxicity Increases p450 (rifampin) Orange body fludis
Rifabutin preferred in HIV patients due to less cytochrome P450 stimulation
Resistance: alteration of structure of DNA dependent RNA polymerase
Pyrazinamide
MOA: thought to acidify intracellular environment via conversion to pyrazinoic acid
Effective in acidic pH of phgaolysosomes where TB is engulfed by macrophages
Clinical: Mycobacterium tuberculosis and intracellular organisms
Toxicity: hyperuricemia, hepatoxicity
Resistance: modified pyrazinamide
Echinocandins
Caspofungin, micafungin, anidulafungin
MOA: inhibits CELL WALL synthesis by inhibiting synthesis of B glucan (1,3 beta D-glucan)
Clinical: invasive aspergillosis, Candida
NOT active against crypto
Toxicity: GI upset, flushing (histamine release)
Suramin and melarsoprol (protozoa)
Trypanosoma brucei
Amphotericin B
MOA: binds ergosterol
Forms membrane pores that allow leakage of electrolytes
Clinical: Serious, systemic mycoses
Cryptococcus (with/without flucytosine), Blastomyces, Coccidioides, Histoplasma, Candida, Mucor
Intrathecally for fungal meningitis
Supplement with K+ and Mg2+ because of altered renal tubular permeability
Toxicity: Thrombophlepbitis, Reactions acutely, Electrolyte imbalances (hypokalemia and hypomagnesium), Anemia (decreases erythropoietin), Dose dependent nephrotoxicity (TREAD lightly with Ampho), fevers chills, hypotension
renal vasoconstriction leads to decreased GFR
Can cause ATN
hypokalemia leads to weakness and arrythmias, tachycardia and fibrillation
Hydration and liposomal amphotericin decreases toxicity
Nystatin
MOA: binds ergosterol
Forms membrane pores that allow leakage of electrolytes
Topical
Clinical: swish and swallow for oral candidiasis
topical for diaper rash or vaginal candidasis
Flucytosine
MOA: inhibits DNA and RNA biosynthesis by conversion to 5-fluoruracil by cytosine deaminase
Clinical: systemic fungal infections (esp. meningitis caused by cryptococcus) in combo with amphotericin B
Toxicity: bone marrow suppression
Griseofulvin
MOA: interferes with microtubule function
Disrupts mitosis
Deposits in keratin-containing tissues
Clinical: oral treatment for superficial infections, inhibits growth of dermatophytes (tinea, ringworm)
Toxicity: Teratogenic, carcinogenic, confusion, headaches, increase P450 and warfarin metabolism
Pyrmethamine (protozoa)
Toxoplasmosis
Terbinafine
MOA: inhibits the fungal enzyme squalene epoxidase (inhibits synthesis of ergosterol)
Clinical: dermatophyses (tinea corporis), especially onychomycosis-fungal infection of toes and fingers
Toxicity:GI upset, hepatotoxicity, taste disturbance
Ehthambutol
MOA: decreases carbohydrate polyemerization of mycobacterium cell wall by blocking arabinosyltransferase
Clinical: mycobacterium tuberculosis
Toxicity: optic neuropathy (red-green color blindness)
Decreased visual acuity, central scotoma,
Hepatotoxicity
Resistance: increased arabinosyl transferase
Nifurtimox (protozoa)
T. cruzi
Foscarnet
MOA: viral DNA polymrease inhibitor and RT inhibitor in HIV
Binds to pyrophosphate binding site of the enzyme
Does not require activation by viral kinase
Clinical: CMV retinitis in immunocompromised patietns when gancyclovir fails
Acyclovir resistant HSV
Toxicity: nephrotoxicity
decreased Ca and MG leading to seizures
Decreased PTH release
Resistance: mutated DNA polymerase
Ribarvirin
MOA: inhibits synthesis of guanine nucleotides by competitively inhibiting inosine monophosphate dehydrogenase
Pairs with uracil or cytosine causing hypermutation during RNA dependent RNA replication
Directly inhibits RNA polymerase
Inhibits guanylyltransferase and methyltransferase resulting in defective 5’ Cap
Enhances TH1 cell mediated immunity while inhibiting TH2 cytokine production
Depletes GTP
Clinical: RSV (infants), chronic hepatitis C
Toxicity: hemolytic anemia, severe teratogen
Cidofovir and tenofovir
MOA: preferentially inhibits viral DNA polymerase
Does not require phosphorylation by viral kinase
Clinical: CMV retinitis in immunocompromised patietns
Acycclovir resitant HSV
Long half life
Toxicity: nephrotoxicity-coadminster with probenecid and IV saline to decrease toxicity
Chloroquine
MOA: blocks detoxification of heme into hemozoin
Heme accumulates and is toxic to plasmodia
Clinical: Treatment of plasmodial species other than P. falciparum
Toxicity: retinopathy, pruritus (dark skinned individuals)
Resistance: membrane pump that decreases intracellular concentration of drug
P. falciparum infection treatment
artermether/lumefantrine
atovaquone/proguanil
Life threatening malaria
quinidine or artesunate
Zanamivir, Oseltamivir
MOA: inhibit influenza neuraminidase leading to decreased release of virus progeny
Clinical: treats and prevents influenza A and B
Slows viral penetration of mucus secretions or respiratory epithelium
Shortens course and complications of influenza A and B if taken within 48 hours
Acyclovir, famciclovir, valacyclovir
MOA: Monophosphorylated (rate limiting) by HSV/VZV thymidine kinase and not phosphorylated in uninfected cells
Guanosine analog
Triphosphate form is active by cellular enzymes
Preferentially inhibits viral DNA polymerase by chain termination
Uninfected cells not affected because uptake is poor, phosphorylation in absence of viral thymidine kinaseis minimal and cellular DNA polymerase has less affinity for acyclovir for acyclovir triphosphate than viral DNA polymerase
Clinical: HSV and VZV
Used for HSV induced mucocutaneous and genital lesions as well as for encephalitis
Prophylaxis in immunocompromised patients
No effect on latent forms
Recurrence suppressed by daily oral intake
Valacyclovir has better oral bioavalability
Toxicity: obstructive crystalline nephropathy and acute renal failure if not adequately hydrated
Resistance: mutated viral thymidine kinase (use foscarnet or cidofiovir for HIV induced resistance-cytidine analog)
Does not work in EBV or CMV because they do not use the same thymidine kinase
Ganciclovir
MOA: 5’-monophosphate formed by a CMV viral kinase
Guanosine analog
Triphosphate formed by cellular kinases
Preferentially inhibits viral DNA polymerase
Valagancicilvoir has better oral bioavailability
Clinical: CMV(retinitis)-immunocompromised
Toxicity: leukopenia, neutropenia, thrombocytopenia, renal toxicity
Resistance: mutated CMV DNA polymerase or lack of viral kinase
Protease inhibitors
-navir
MOA: assembly of virions depends on HIV-1 protease (pol gene) which cleaves the polypeptide products of HIV mRNA into their functional parts
Prevent maturation of new viruses
Ritonavir-inhibits cytochrome p450
Toxicity: hyperglycemia, GI intolerance, lipodystophy (ipoared hepatic chylomicron uptake and triglyceride clearance)
Nephropathy and hematuria (indinavir)
Azoles
Fluconazole, ketoconazole, clotrimazole, miconazole, itraconazole, voriconazole
MOA: inhibit fungal sterol (ergosterol) synthesis by inhibiting cytochrome p450 enzyme that converts lanosterol to ergosterol
Clinical: local and less serious systemic mycoses
Fluconazole for chronic suppression of cryptococcal meningitis in AIDS patients and candidal infections
Itraconazole for balstomyces, coccidiodes, histoplasma
Clotrimazole and miconazole for topical fungal infections
Toxicity: testerosterone synthesis inhibition (gynecomastia esp. ketoconazole), liver dysfunction (inhibits cytochrome p450)
Daptomycin
MOA: depolarization of the cellular membrane
Creates cell membrane channels causing leakage of intracellular ions and inhibition of DNA, RNA, and Protein syntesis
Treats: skin infections and bacteremia (with or without endocarditis), due to S. Aureus including MRSA
Inactivated by pulmonary surfactant-don’t use in pneumonia
Toxicity: increased CPK and myopathy
don’t use in pregnancy and adverse effect
Sulfonamides-kernicterus Aminoglycosides-ototoxicity Fluroquinolones-cartilage damage Clarithromycin-embryotoxic Tetracyclines-discolored teeth, inhibition of bone growth Ribavirin-tertogenic Griseofulvin-terotogenic Chlroramphenicol-gray baby
Sodium stibogluconate (protozoa)
leishmaniasis
Typical HIV therapy regimen
2 nucleoside RT inhibitors +
1 non-nucleoside RT inhibitor or 1 protease inhibitor or 1 integrase inhibitor
NRTIs
LT DAZES
Lamivudine, Tenofovir, Didanosine, Abacavir, Zidovudine, Emtricitabine, Stavudine
MOA: competitively inhibit nucleotide binding to reverse transcription and terminate the DNA chain
Disrupts 3’-5’ phosphodiester bond formation
Tenofovir is the only nucleotide
Nucleosides need to be phosphorylated to be active
ZDV is used for prophylaxis and during pregnancy to decrease risk of fetal transmission
ZDV inhibits cellular and mitochondrial DNA polymerases-watch with gancyclovir co-adminstration
Toxicity: bone marrow suppression (reversed with G-CSF and erythropoietin), peripheral neuropathy, lactic acidosis (nucleosides), rash (non-nucleoside), anemia (ZDV), pancreastitis (didanosine)
NNRTIs
Efavirenz, nevirapine, Delavirdine
(END)
MOA: bind to reverse transcriptase at site different than NRTIs
Do not require phosphorylation to be active
Toxicity: flu like symptoms, abdominal pain, jaundice, steven johnsons syndrome, or toxic epidermial necorlysis
Rash and hepatoxicity
Vivid dreams and CNS symptoms with efavirenz
Delvirdine and efavirenz CI in pregancy
Raltegravir
Integrase inhibitor
MOA: inhibits HIV genome integration into host cell chromosome by reversibly inhibiting HIV integrase
Inhibiting mRNA transcription
Toxicity: hypercholesterolemia
Enfurvirtide
Fusion inhibitor
MOA: binds gp41 inhibiting viral entry
Toxicity: skin reactions at injection site
Maraviroc
Fusion inhibitor
MOA: binds CCR5 on surface of T cells/monocytes
inhibiting interaction with gp120
1st gen Cephalosporins
Cefazolin, cephalexin)
MOA: Inhibit cell wall synthesis but less susceptible to penicillinases
Bacterocidal
Irreversibly binds to penicillin binding proteins (transpeptidases)
Clinical: Gram+ cocci, Proteus, E. Coli, Klebsiella
Cefazolin used prior to surgery to prevent S. aureus wound infections
Toxicity: hypersentivity reactions, vitamin K deficiency, low cross reactivity with penicillins
Increase nephrotoxicity of aminoglycosides
Resistance: change in protein structure in penicillin binding proteins
Interferons
MOA: Glycoproteins normally synthesized by virus-infected cells
Wide range of antiviral and antitumoral properties
Clinical: IFN-a: chronic hep B and C, Kaposi, hairy cell luekemia, condolyloma acurmintum, renal cell carcinoma, malignant melanoma
IFN-B: MS
IFN-y: CGD
Toxcity: neutropenia, myopathy
Dapsone
MOA: inhibits bacterial synthesis of dihydrofolic acid through competitive inhibition of dihydropteroate synthetase
Clinical: second line prophylaxis for pneumocystis pneumonia
Toxicity: fever, rash, methehemoglobinemia, agranuolocytosis
Causes hemolysis in G6PD
Fidaxomicin
Inhibits RNA polymerase
Given orally with minimal systemic absorption
Used for recurring C. Difficile
Palvizumab
Ab against F protein used to prevent pneumonia caused by RSV in premature infants
Specific indinavir (protease inhibitor) side effect
Nephrotoxicity and nephrolithiasis
Adequately hydrate to avoid
Specific didanosine side effect
Pancreatitis
Specific abacavir side effect
Hypersensitivity
NRTIs specific side effect
Lactic acidosis
Specific NNRTIs
Stevens Johnson syndrome
Specific nevirapine side effect
Liver failure
