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ANTIBIOTICS A brief overview for DMAT PA-1

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1 ANTIBIOTICS A brief overview for DMAT PA-1
Saundra J. Martino RpH

2 DEFINITIONS *Antibiotic- agents derived from natural sources (bacteria or molds) used to treat infection by suppressing or destroying the causative microorganism *Antimicrobial- those anti-infective agents which are derived from synthetic substances * these two terms are now used interchangeably Antiseptic- an agent used to inhibit bacterial growth Bacteria- microscopic single-celled organisms containing DNA and cell walls Bactericidal- kills the bacteria Bacteriostatic- inhibits the growth of the bacteria Disinfectant- an agent used to kill bacteria Normal flora-non-pathogenic bacteria that live on human skin and mucous membranes Pathogen-bacteria that cause disease Spectrum of activity- a product’s range of antimicrobial activity

I. Shape Spherical (cocci) single cells (micrococci) pairs (diplococci) clusters (staphylococci) chains (streptococci) cubical groups (sarcinae) Rod-like (bacilli) oval shapes (coccobacilli) chains (streptobacilli) Spiral (spirochetes) rigid (spirilla) flexible (spirochetes) curved (vibrios) II. Stain (gram-stain) gram-positive (stains blue) * gram-negative (stains pink) * have a unique outer membrane that prevents many drugs from penetrating them—making them more resistant to antibiotics III. Use of oxygen aerobic—require oxygen to live anaerobic---live in the absence of oxygen thrive in areas of the body with low levels of oxygen (intestines, decaying tissue, deep and dirty wounds—they tend to invade skin and muscle tissue that has been damaged) facultative---can live and grow in the presence or absence of oxygen

4 COMMON EXAMPLES Gram-positive aerobes Gram-positive anaerobes
streptococcus pneumoniae *pericarditis,pneumonia,acute sinusitis, meningitis, otitis media, septicemia enterococcus faecalis *burn wound sepsis, infective endocarditis staphylococcus aureus *pneumonia, cellulitis, boils, toxic shock, postoperstive bone and joint infections, peritonitis, styes, suppurative conjunctivitis, staphylococcus epidermis *human bites,burns,IV line infections, postoperative bone and joint infections bacillus anthracis *anthrax corynebacterium diphtheriae *pharyngitis, tonsilitis, diphtheria streptococcus agalactiae (group B streptococcus) *bacterial sepsis and meningitis in newborns, endometritis and fever in postpartum streptococcus pyogenes (group A streptococcus) *diabetic foot ulcers, pharyngitis, tonsilitis, burns, cellulitis, decubitus ulcers, impetigo, toxic shock, necrotizing fasciitis, scarlet fever, rheumatic fever Gram-positive anaerobes clostridium difficile *pseudomembraneous colitis clostridium botulinum *botulism clostridium tetani *tetanus clostridium perfringens *gas gangrene

5 Gram-negative aerobes neisseria meningitidis
*meningitis escherichia coli *urinary tract infections, pyelonephritis, septicemia, gastroenteritis, peritonitis neisseria gonorrhoeae *gonorrhea, pelvic inflammatory disease pseudomonas aeruginosa *puncture wounds, complicated urinary tract infections (catheter related), burns, pneumonia (ventilator related) haemophilus influenzae *pneumonia, meningitis, otitis media, acute sinusitis moraxella catarrhalis *pneumonia klebsiella pneumoniae * wounds, otitis media, aspiration pneumonia legionella sp. * Legionnaires’ disease shigella sp. *severe diarrhea, gastroenteritis salmonella sp. *severe diarrhea, gastroenteritis, salmonella bacteremia campylobacter jejuni *diarrhea Gram-negative anaerobes bacteroides fragilisclo *sepsis

Aminoglycosides B-lactams *Penicillins *Cephalosporins *Carbapenems Macrolides Quinolones Sulfonamides Tetracyclines Miscellaneous Agents *Vancomycin *Clindamycin *Metronidazole *Fluconazole *Terconazole *Miconazole *Nystatin *Rifaximin *Nitrofurantoin *Mebendazole *Bacitracin *Triple antibiotic ointment *Neomycin/polymyxin B/hydrocortisone otic suspension

7 AMINOGLYCOSIDES Miscellaneous facts: bactericidal
*”concentration-dependent killing”—the bactericidal effect increases as the antibiotic concentration increases *”post-antibiotic effect” – continues to inhibit bacterial growth for several hours after aminoglycoside concentrations are no longer detectable higher doses at longer intervals often used in combination with B-lactam antibiotics to achieve antibacterial synergy to treat serious pneumococcal and enterococcal endocarditis no oral absorption – must give IV/IM rapid renal excretion poor CNS penetration clinical differences among the agents are subtle Spectrum:gram-negative enterobacteria no activity against anaerobes Therapeutic uses: suspected sepsis, pneumonia, meningitis, complicated urinary tract infections, osteomyelitis, bacteremia, peritonitis Drawbacks: very limited by their toxic potential ototoxic (irreversible) and nephrotoxic nephrotoxicity: more common than ototoxicity, often reversible, most common in the elderly and those concurrently receiving amphotericin B, cephalosporins, or vancomycin accumulate in the proximal tubule of the kidney –mild renal dysfunction occurs in 25% of patients on these drugs for several days or more once daily dosing has been reported to be effective and less nephrotoxic caution in patients with decreased renal function caution with other ototoxic and nephrotoxic drugs neuromuscular blockade can occur with high doses, rapid IV administration, in addition to neuromuscular blocking agents or anaesthetics, hypocalcemia, myasthenia gravis, and with blood transfusions Pregnancy category D Monitoring parameters:blood draws—peaks & troughs, BUN, serum creatinine levels BLACK BOX WARNING nephrotoxicity & ototoxicity

8 Gentamicin(Garamycin)IV/IM
More active than tobramycin against serratia organisms (septicemia) Activity against mycobacterium and e.coli Used in combination with other antibiotics to treat staph. aureus and certain species of streptococcus Serum concentrations are unpredictable after IM administration—IV is the preferred route Gentamicin ophth soln (Garamycin) Potential ocular irritation and burning Tobramycin (Nebcin)IV/IM Better activity than gentamicin against pseudomonas aeruginosa (puncture wounds,urinary tract infections,burns, pneumonia) Some studies suggest it is less nephrotoxic than gentamicin—not firmly established Used in combination with other antibiotics to treat staph. aureus and certain species of streptococcus IV is the preferred route of administration Amikacin Kanamycin Neomycin Netilmicin Streptomycin Paromomycin

9 B-LACTAMS Miscellaneous facts:
contain a unique 4 member ring that is essential for antibacterial activity certain bacteria produce and enzyme (B-lactamase) that breaks the ring and inactivates the antibiotic B-lactamase producing bacteris: staph. Aureus h. influenzae bacteroides sp. pseudomonas sp. legionella sp. drug interaction with probenecid—probenecid inhibits renal excretion of the antibiotics causing higher, prolonged serum levels anaphylactic reactions are common (urticaria, laryngeal edema,bronchospasm) *Penicillins *Cephalosporins *Carbapenems

10 PENICILLINS Miscellaneous facts:bactericidal Spectrum:broad spectrum
Four Subdivisions *Natural Penicillins *Aminopenicillins *Penicillinase-Resistant Penicillins *Extended-Spectrum Penicillins Spectrum:broad spectrum gram-positive and gram-negative Therapeutic uses:oropharyngeal infections, sexually transmitted diseases, pharyngitis, otitis media, sinusitis, bacteremia, anthrax, skin and soft tissue infections, mild respiratory infections, uncomplicated urinary tract infections Drawbacks: resistance hypersensitivity reactions (occur in up to 10% of people receiving penicillins) bone marrow depression gastrointestinal distress potential to cause seizures when given in high doses to patients with renal dysfunction ticarcillin and carbenicillin can cause platelet dysfunction

11 NATURAL PENICILLINS Miscellaneous facts:
highly active against gram-positive cocci and gram-negative cocci most common use is for streptococcus sp. Penicillin G Sodium (Pfizerpen) IV/IM Penicillin VK (Veetids) oral Penicillin G procaine repository form IM use only Penicillin G benzathine

12 AMINOPENICILLINS Miscellaneous facts: broad-spectrum penicillins
their spectrum is similar to but broader than that of the natural and penicillinase-resistant penicillins ineffective against most staphylococcal organisms commonly used for upper respiratory infections, uncomplicated urinary tract infections and otitis media Amoxicillin oral capsules & suspension semisynthetic agent better absorption and less frequent dosing than ampicillin better bioavailability than penicillin—more stable to gastric acid Amoxicillin/clavulanic acid (Augmentin)oral chewables, tablets and suspension clavulanic acid—no antibacterial activity, it inhibits B-lactamase by binding to it and inactivating it-therefore increasing the spectrum of activity of amoxicillin clavulanic acid causes a high incidence of gastrointestinal effects more effective than amoxicillin against staph. aureus, klebsiells sp., and bacteroides fragilis Ampicillin sodium IV/IM more effective than amoxicillin against shigellosis sp. Ampicillin sulbactam (Unasyn) IV

Miscellaneous facts: active against gram-positive aerobes limited activity against gram-negative and anaerobic bacteria are not inactivated by B-lactamase less potent than natural penicillins against organisms susceptible to natural penicillins– cannot substitute for natural penicillins complete cross-resistance exists among the group all are identical except for their route of administration commonly used for bacteremia, skin and soft tissue infections, respiratory tract infections, bone and joint infections, urinary tract infections ineffective against MRSA/MRSE Dicloxacillin(Dynapen)oral capsule food decreases oral bioavailibility—administer on an empty stomach Nafcillin(Nallpen)IM/IV semisynthetic metabolized by liver – useful in patients with renal impairment associated with neutropenia in 10 to 20% of patients multiple drug interactions (warfarin,etc.) Cloxacillin Methicillin Oxacillin

Miscellaneous facts: also known as antipseudomonal penicillins have broadest spectrum of all penicillins used to treat serious infections caused by gram-negative aerobes ineffective against staphylococci sp. hypersensitivity reactions are more common in this subdivision all inhibit platelet aggregation– result in bleeding Piperacillin Piperacillin/tazobactam (Zosyn)IV tazobactam—no antibacterial activity, inhibits B-lactamase therefore enhancing the intrinsic activity of piperacillin—increased gastrointestinal side effects most potent extended-spectrum penicillin against pseudomonas sp. effective in treatment of nosocomial pneumonia Ticarcillan Ticarcillin/clavulanic acid

15 CEPHALOSPORINS Miscellaneous facts: B-lactam antibiotics
bactericidal 4 generations classified according to their spectrum of activity each generation increases its gram-negative activity but, loses activity against gram-positive organisms popular due to their low toxicity and activity against serious infections Spectrum: gram-positive and gram-negative no activity against MRSA Therapeutic uses:perioperative prophylaxis, urinary tract infections, acute otitis media, sinusitis, etc Drawbacks: most are eliminated via renal excretion—adjust dosages in renal insufficiency hypersensitivity reactions (fever, maculopapular rash, anaphylaxis, & hemolytic anemia) gastointestinal effects hypoprothrombinemia potential for nephrotoxicity cross-sensitivity with penicillins in up to 10% of patients receiving cephalosporins

Miscellaneous facts: oldest cephalosporins gram-positive activity & basic gram-negative activity (except enterococci) widely used for perioperative prophylaxis used to treat klebsiella sp., skin and soft tissue infections, respiratory tract infections, otitis media Cefazolin(Ancef)IM/IV compared to other 1st generation cephalosporins it achieves higher blood levels after administration, has greater gram-positive coverage and requires less frequent dosing Cephalexin(Keflex) oral capsules ,oral suspension primarily used for otitis media and respiratory tract infections Cephadroxil Cephradine

Miscellaneous facts: less gram-positive coverage & more gram-negative coverage than 1ST generation cephalosporins also active against B-lactamase producing strains of haemophilius influenzae Cefaclor Cefoxitin Cefprozil Cefuroxime Cefotetan

Miscellaneous facts: increased gram-negative coverage & decreased gram-positive coverage over 2nd generation cephalopsorins best CNS penetration of all cephalosporins—very valuable in treatment of meningitis caused by meningococci, pneumococci, haemophilus influenzae, and enteric gram-negative bacilli especially useful for gram-negative upper respiratory tract infections, otitis media, urinary tract infections and skin infection empiric therapy for life-threatening infections in which resistant organisms are the most likely cause treatment of sepsis of unknown origin in immunosuppressed patients initial therapy in mixed bacterial infections Cefotaxime(Claforan)IM/IV commonly used to treat empiric gram-negative meningitis, serious bacteremias, pneumonia, and community-acquired infections Ceftriaxone(Rocephin)IM/IV longest half-life of all cephalosporins allowing for once daily dosing DOC=neisseria gonorrhoeae Cefdinir Cefixime Cefoperazone Cefopodoxime proxetil Ceftazidime Ceftibuten Ceftizoxime Cefditoren

19 4th Generation Cephalosporins
Miscellaneous facts: newest cephalosporins same coverage as 3rd generation cephalosporins with additional coverage against pseudomonas sp high degree of resistance to B-lactamase producing organisms good activity against organisms that are resistant to 3rd generation cephalosporins commonly used for febrile neutropenic patients Cefepime (Maxipime)

20 CARBAPENEMS Miscellaneous facts: B-lactam antibiotics
bactericidal Spectrum:gram-positive cocci, gram-negative rods, and anaerobes broader spectrum than most B-lactams Therapeutic uses:urinary tract infections, lower respiratory tract infections, gangrene, sepsis, pneumonia,intra-abdominal infections, gynecological infections, etc. Drawbacks: anaphylactic reactions, seizures, confusion, dizziness, gastrointestinal issues Imipenem/cilastatin Ertapenem Meropenem

21 MACROLIDES Miscellaneous facts:
mostly bacteriostatic—can be bactericidal newer macrolides-better absorption and less gastrointestinal effects Spectrum: gram-positive cocci and bacilli & some gram-negative cocci mycoplasma pneumoniae, chlamydia trachomatis, legionella sp., corynebacterium diphtheriae, campylobacter sp., treponema pallidum, propionibacterium acnes, & borrelia burgdorferi DOC=group A streptococcal and pneumococcal infections when penicillin cannot be used Therapeutic uses: Legionnaires disease, dental prophylaxis , chlamydial infections, ance, diphtheria, pertussis, ocular infections Drawbacks: numerous drug interactions – erythromycin inhibits the hepatic metabolism of other drugs (theophylline, digoxin, corticosteroids, carbamazepine, cyclosporin, lovastatin, etc.) cardiac issues—causes QT prolongation and torsade de pointes gastrointestinal disturbances (dose-related),skin rashes, eosinophilia, tinnitus, dizziness, reversible hearing loss

22 Erythromycin base (ERYTAB) oral tablet enteric coated, delayed-release tabs (do not crush)
DOC=Legionnaire’s disease, mycoplasma pneumonia and chlamydial infections drug interactions with terfenadine, astemizole, pimozide, etc dose must be decreased with decreased liver function pregnancy category B Erythromycin ethylsuccinate(EES) oral suspension Erythromycin ophth oint. superficial ocular infections prophylaxis of neonatal ophthalmia due to neisseria gonorrhoeae or chlamydia trachomatis Azithromycin(Zithromax, Z-Pak) oral suspension,oral tablets semisynthetic macrolide less active than erythromycin against gram-positive organisms more active than erythromycin against haemophilus influenzae and other gram-negative organisms concentrates in cells– tissue levels are higher than serum levels—increased efficacy and duration of action-less tendency to cause drug interactions once daily dosing less gastrointestinal issues than with other macrolides very useful in nongonococcal urethritis caused by chlamydia, lower respiratory tract infections, mycobacterium avium complex infection, pharyngitis, pelvic inflammatory disease, nongonococcal urethritis caused by chlamydia, Legionnaire’s disease pregnancy category B Clarithromycin(Biaxin) XL oral tablets, oral suspension semisynthetic macrolide same spectrum as erythromycin –more potent enhanced activity against haemophilus influenzae and mycobacterium avium complex also active against toxoplasma gondii, and cryptosporidium sp. metalic aftertaste pregnancy category C Erythromycin estolate Erythromycin stearate Dirithromycin

23 QUINOLONES Miscellaneous facts:
bactericidal (concentration dependent) 4 generations – each generation adds coverage for a new group of pathogens different mechanism of action -- thus, no cross resistance with other classes of antibiotics produce a false-positive urine screening result for opiates when using a commercially available immunoassay kit Spectrum: highly active against gram-negative aerobes & gram-positive activity no activity for most anaerobes Therapeutic uses: urinary tract infections, lower respiratory tract infections, sinusitis, otitis media, infectious diarrhea, prostatitis, empiric use in febrile neutropenic patients Drawbacks: relatively free of side effects and toxicity phototoxicity not recommended in children under 18 years of age (cartilage malformations were found in studies in immature animals),tendon rupture, cardiac QT prolongation( associated with 2nd and 3rd generations), CNS stimulation, hypoglycemia, seizures, anaphylactic reactions, pseudomembraneous colitis, can cause exacerbation of myasthenia gravis multiple drug interactions – theophylline, antacids, iron, multivitamins, warfarin, NSAIDs (potential to increase risk of seizure), antiarrhythmic drugs pregnancy category C

Miscellaneous facts: bactericidal gram-negative coverage (excluding pseudomonas) limited use due to the development of bacterial resistance poor oral availability limits its systemic use common uses include urinary tract infections Nalidixic acid

Miscellaneous facts: bactericidal increased gram-negative coverage (including pseudomonas), gram-positive cocci, and mycobacteria addition of fluorine ion to the quinolone structure =fluoroquinolones QT prolongation and torsade de pointes Ciprofloxacin (cipro)oral tablets/IV good penetration into bone—useful in osteomyelitis urinary tract infections, lower respiratory tract infections, sinusitis, empiric use in febrile neutropenia, typhoid fever, infectious diarrhea, prostatitis, bacterial conjunctivitis, corneal ulcers, nosocomial pneumonia indicated for use in mycobacterium avium complex in patients with AIDS

used in combination with other drugs to treat multi-drug-resistant tuberculosis most potent flouruquinolone against pseudomonas aeruginosa no longer drug of choice for neisseria gonorrhoeae (becoming resistant) absolute contraindication: tendon pain, tendon rupture, tendonitis oral dosage equivalent IV dosage 250mg q12h mg IV q12h 500mg q12h mg IV q12h 750mg q12h mg IV q8h Ofloxacin (Floxin,Ocuflox) oral/ophth/otic use less potent than ciprofloxacn against most gram-negative bacteria most active 2nd generation against chlamydia trachomatis Norfloxacin (Noroxin, Chibroxin)

Miscellaneous facts: QT prolongation bactericidal extended gram-positive coverage (particularly against penicillin-sensitive and penicillin-resistant streptococcus pneumoniae, mycoplasma pneumoniae & chlamydia pneumoniae) gram-negative coverage (including pseudomonas sp.) decrease dosage in renal impairment treatment of community-acquired pneumonia, acute sinusitis, acute exacerbations of chronic bronchitis, bacterial conjunctivitis Gatifloxacin ophthalmic, bacterial conjunctivitis Levofloxacin oral, IV, ophthalmic less QT prolongation than with other fluoroquinolones Moxifloxacin oral,IV, ophthalmic not used for urinary tract infections approved for treatment of complicated intra-abdominal infections

Miscellaneous facts: bactericidal gram-positive & gram-negative significant coverage against anaerobes Trovafloxacin (Trovan) restricted by FDA to serious life-or-limb-threatening infections due to serious drug induced hepatic adverse effects BLACK BOX WARNING: treatment restriction limitations—hospitals and long term care facilities liver injury leading to liver transplantation and or death

29 SULFONAMIDES Miscellaneous facts: bacteriostatic
Spectrum: mostly gram-positive, some gram-negatives also activity against certain strains of chlamydia trachomatis, nocarida, actinomyces, & bacillus anthracis Therapeutic uses: animal and human bites, urinary tract infections, otitis media, chronic bronchitis, travelers’ diarrhea, sexually transmitted bacterial infections, ocular infections and burns Drawbacks:photosensitivity, can cause Stevens-Johnson syndrome, hypersensitivity reactions, blood dyscrasias, caution in patients with G6PD deficiency (can cause acute hemolysis), crystalluria, hematuria drug interactions with phenytoin, oral anticoagulants, & sulfonylureas cross-allerginicity between the individual sulfonamides discontinue at first sign of skin rash or other reaction SMZ/TMP(Bactrim,BactrimDS) (sulfamethoxazole/trimethoprim)->synergistic combination bacteriostatic-in combination with trimethoprim=bactericidal DOC=treatment and prophylaxis of pneumocystis carinii useful in acute gonococcal urethritis, acute exacerbation of chronic bronchitis Sodium Sulfacetamide 10% ophth soln Used to treat conjunctivitis or superficial bacterial eye infections,corneal ulcers can cause a delay in corneal wound healing local irritation, burning, stinging Silver sulfadiazine1% cream(Silvadene) bactericidal gram-positive & gram-negative --- some effectiveness against yeast adjunct for prevention and treatment of wound sepsis in patients with 2nd & 3rd degree burns

30 TETRACYCLINES Miscellaneous uses:
bacteriostatic cross-resistance with the group is extensive Spectrum: gram-negative & gram-positive broad spectrum agents—coverage includes spirochetes, rickettsia, mycoplasma pneumonia, chlamydia sp., & certain protozoa species Therapeutic uses: DOC=rickettsial (Rocky Mountain Spotted Fever), chlamydial, mycoplasmal infections, anthrax frequently used for acne and periodontitis useful alternative to penicillin in treatment of anthrax, syphilis, gonorrhea, Lyme disease, and h. influenzae respiratory infections Drawbacks: photosensitivity gastrointestinal distress, hypersensitivity reactions, hepatoxic (especially in pregnant women), pregnancy category D, tooth discoloration (binds to calcium in teeth & bones-enamel hypoplasia can also occur), not recommended in children<8 years old, cannot give with antacids or milk, cannot use tetracycline after expiration date(causes renal tubular dysfunction which can lead to renal failure), take with fluids to avoid esophageal irritation Doxycycline (Vibramycin) oral tablets excreted mainly in feces –very useful in patients with poor renal function Minocycline Tetracycline

31 MISCELLANEOUS AGENTS Vancomycin (Vancocin)IV peaks:20-40mcg/ml
Miscellaneous facts: bactericidal troughs:5-15mcg/ml very useful in patients allergic to penicillins or cepphalosporins Spectrum: gram-positive organisms including MRSA/MRSE and enterococci Therapeutic uses:serious infections—endocarditis, osteomyelitis, staphylococcal pneumonia, treatment of pseudomembranous colitis caused by c.difficile or s.aureus enterocolitis oral form used only for c. difficile Drawbacks: ototoxicit y increased ototoxicity & nephrotoxicity when given with other ototoxic and nephrotoxic drugs monitor blood levels hypersensitivity reactions facial flushing and hypotension with too rapid infusion of the drug (red man syndrome) Clindamycin (Cleocin)oral/IV/IM Miscellaneous facts: bacteriostatic cross resistance with macrolides is common reserve for serious infections in patients with penicillin allergies does not diffuse into cerebrospinal fluid—do not use for meningitis Spectrum:most gram-positive & many anaerobic organisms bacteroides fragilis Therapeutic uses: skin, respiratory tract, and soft tissue infections caused by staphylococci, pneumococci, and streptococci, dental infections, acne, bone & joint infections, bacterial vaginosis Drawbacks: limited by its toxicities gastrointestinal issues, blood dyscrasias, Stevens-Johnson syndrome dose must be decreased with impaired hepatic function potentiates the effects of neuromuscular blocking agents BLACK BOX WARNING first antibiotic to be associated with pseudomembraneous colitis c. difficile associated diarrhea (pesudomembranous colitis) alters the colon flora which leads to c.difficile overgrowth c.difficile produces toxins A and B which contribtes to c.difficile associated diarrhea

32 Metronidazole(Flagyl) oral/IV
Miscellaneous facts:antibacterial and antiprotozoal agent amebicide—amebicidal and trichomonacidal Spectrum:anaerobic gram-positive and anaerobic gram-negative certain protozoan parasites (trichomonas vaginalis, entamoeba histolyticass, giardia lamblia,etc.) DOC=c.difficile, bacterial vaginosis (gardnerella vaginalis), c. tetani Therapeutic uses:amebic dysentery, giardiasis, trichomoniasis, intra-abdominal, pelvic, soft tissue, periodontal, and odontogenic infections, lung abscess, acne, meningitis, bacterial septicemia, lower respiratory tract infections, endocarditis Drawbacks: hepatic metabolism-dosage adjustment in patients with liver dysfunction gastrointestinal distress, headache, dark coloration of urine, leukopenia, dizziness, ataxia disulfiram-like reaction with ethanol inhibits warfarin metabolism-increased bleeding metallic taste use cautiously in pregnancy (avoid in first trimester) drug interactions: warfarin, phenytoin, phenobarbital, cimetidine, lithium, etc. absolute contraindication in breast feeding use with caution in patients with evidence of or history of hematological disease Fluconazole(Diflucan) oral tablet Miscellaneous facts: azole antifungal agent fungistatic Spectrum:active against many fungi, including yeasts, dermatophytes, actinomycegtes, and some phycomycetes, cryptococcus, candida, aspergillis Therapeutic uses:vaginal candidiasis, oropharyngeal and esophageal candidiasis, systemic candida infections and cryptococcal meningitis DOC=cryptococcal meningitis Drawbacks:gastrointestinal disturbances, skin rashes, hepatic necrosis, Stevens-Johnson syndrome, anaphylaxis, alopecia multiple drug interactions: phenytoin, cyclosporine, warfarin,sulfonylureas, etc pregnancy category C

33 Terconazole cream (vaginal)
Miscellaneous facts: fungicidal Spectrum:candida albicans active against dermatophytes, yeasts, and at high concentrations gram-positive & gram-negative bacteria Therapeutic uses: complicated and uncomplicated vulvovaginal candidiasis Drawbacks: pruritis, irritation-vulvovaginal burning, headache, body pain pregnancy category C (not recommended during first trimester) Miconazole cream 2% Miscellaneous facts: imidazole antifungal agent fungistatic topical or intravaginal use Spectrum:broad spectrum blastomyces dermatitidis, candida sp., cryptococcus neoformans, coccidioides immitis, histoplasma capsulatum, paracoccidioides brasiliensis, sporothrix schenckii Therapeutic uses: for topical and vaginal fungal infections (vaginal candidiasis, tinea infections, cutaneous candidiasis) Drawbacks: pregnancy category C Nystatin cream Miscellaneous facts: antifungal agent fungicidal and fungistatic Spectrum: primary activity against candida sp ineffective against bacteria, protozoa, trichomonads, and viruses Therapeutic uses: treatment of oropharyngeal, cutaneous, mucocutaneous and vulvovaginal candidiasis poor oral absorption, good local activity—great choice for oral and esophageal candida infections Drawbacks: oral form causes gastrointestinal distress contact dermatitis, Stevens-Johnson syndrome not administered systemically due to potential toxicity

34 Loperamide(Imodium) oral capsules
Rifaximin(Xifaxan) oral tablets Miscellaneous facts: rifamycin antibiotic non-systemically absorbed-no significant drug interactions Spectrum: gram-positive, gram-negative, aerobes, anaerobes Therapeutic uses: Traveler’s diarrhea caused by non-invasive strains of e.coli Drawbacks: do not administer to patients with diarrhea complicated by fever or blood in the stools flatulence, headache, abdominal pain, nausea, constipation, pyrexia caution in patients allergic to any of the rifamycin antimicrobial agents not for use in children under 12 years of age pregnancy category C—if necessary—only in 2nd and 3rd trimesters poor GI absorption-no systemic bioavailability-no drug interactions 200mg tid for 3 days Loperamide(Imodium) oral capsules Miscellaneous facts: synthetic antidiarrheal for oral use prolongs transit time of the intestinal contents (decreases peristalsis), reduces daily fecal volume, increases viscosity and bulk density---diminished loss of fluids and electrolytes Spectrum: Therapeutic uses: control and symptomatic relief of acute nonspecific diarrhea and of chronic diarrhea associated with inflammatory bowel disease—also used for reducing the volume of discharge from ileostomies Drawbacks: dry mouth, flatulence, abdominal cramps and colic not recommended in infants under 24 months of age 2 capsules initially then, 1 capsule after each loose stool max 8 capsules (16mg) capsules per 24 hour make sure patient receives appropriate fluid and electrolyte replacement tolerance to the antidiarrheal effect has not been observed

35 Mebendazole (vermox) oral tablet
Nitrofurantoin Miscellaneous facts: bacteriostatic-can be bactericidal in high concentrations urinary tract antiseptic/bladder antiseptic concentrates in the renal tubules and bladder – doesn’t achieve blood levels high enough to treat systemic infections Spectrum:gram-positive and gram-negative Therapeutic uses:prevention and treatment of uncomplicated urinary tract infections caused by escherichia coli or staphylococcus saprophyticus Drawbacks:gastrointestinal issues fairly common hypersensitivity reactions, headache, vertigo, dizziness polyneuropathy ---with high doses or patients with renal impairment monitoring parameters BUN, CrCl, LFT’s Mebendazole (vermox) oral tablet Miscellaneous facts: anthelmintic death of the worm is slow—complete gastrointestinal clearance up to 3 days after therapy retreatment necessary if patient not cured in 3 weeks Spectrum: ancylostoma duodenale (hookworm) ascaris lumbricoides (roundworm) enterobius vermicularis (pinworm) necator americanus (American hookworm) trichuris trichiura (whipworm) Therapeutic uses: DOC= GI hematodes Drawbacks: drug interactions : carbamazepine and phenytoin abdominal pain, nausea, diarrhea myelosuppression can occur with high doses

36 Triple antibiotic ointment
Bacitracin ointment Miscellaneous facts: bacteriostatic– potential to be bactericidal Spectrum: gram-positive bacteria Therapeutic uses: topical use to prevent superficial skin infections following minor injuries on small areas of the body Drawbacks: caution in patients with neomycin hypersensitivity maximum duration of use = 7 days incidence of contact dermatitis is about 2 % Triple antibiotic ointment Miscellaneous facts: (neomycin/polymyxin B/bacitracin) Spectrum: gram-positive and gram-negative (neomycin & polymyxin B both have gram-negative coverage) Therapeutic uses: superficial skin infections Drawbacks: can cause allergic dermatitis neomycin containing products can cause allergic reactions in about 1 in 20 people

37 Neomycin/polymyxin/hc otic susp
Miscellaneous facts: antibacterial & anti-inflammatory Spectrum:gram-negative aerobes MRSA coverage Therapeutic uses: superficial bacterial infections of the external auditory canal maximum use = 10 days Drawbacks: caution in patients with tympanic membrane perforation or chronic otitis media – risk of ototoxicity allergic skin reactions pregnancy category c

38 QUIZ 1.Which antibiotic is associated with “red man syndrome”?
A.) clindamycin B.) vancomycin C.) penicillin D.) ciprofloxacin 2.Which injectable cephalosporin is the drug of choice for neisseria gonorrhea? A.) Ancef B.) Rocephin C.) Claforan D.) Mefoxin 3. Why should you not use tetracycline after the expiration date? A.) renal failure B.) hepatic failure C.) QT prolongation D.) diarrhea 4.Which antibiotic is not included in the DMAT cache? A.) Rocephin B.) Amoxicillin C.) Levaquin D.) Cephalexin 5. How many generations of quinolones are there? A.) 1 B.) 2 C.) 3 D.) 4

39 References Lacy C, Armstrong L,Goldman M, Lance L, Lexi-Comp’s Drug Information Handbook, 15th edition, 2007 Beers M, Porter R, Jones T, Kaplan J, Berkwits M, The Merck Manual,18th edition, 2006 Shargel L, Mutnick A, Souney P, Swanson L, Comprehensive Pharmacy Review, 6th edition, 2007 Gilbert D,Moellering R, Eliopoulos G, Chambers H, Saag M, The Sanford Guide To Antimicrobial Therapy 2009 (39th edition), 2009 Trevor A, Katzung B, Masters S, Pharmacology Examination and Board Review, 8th edition, 2008 Clinical Pharmacology, online Epocrates Online, online Doxycycline hyclate capsules package insert. Eatontown, NJ; West-ward Pharmaceutical Corp.; 2006 July Fluconazole tablets package insert. Miami, Fl; Ivax Pharmaceuticals, Inc.;2006 Azithromycin tablets package insert. Peapack, NJ;Greenstone Ltd.;2007 August Clarithromycin package insert. Jerusalem, Israel: Teva Pharmaceutical IND. LTD ;2008 Jan Erythromycin Base Filmtab package insert. Chicago,Il.;Abbott Laboratories; 2004 Nov Nystatin package insert. Ontario, Canada; Taro Pharmaceuticals Inc.;2005 June Erythromycin ophth. Ointment package insert. Melville, NY;E.Fougera & Co.;1999 Metronidazole tablets package insert.Pomona NY; Pliva Krakow Pharmaceutical Company;2007 May Ciprofloxacin package insert. Miami,Fl.:Ivax Pharmaceuticals Inc;2007 Feb Terconazole vaginal cream package insert.Hawthorne NY;Taro Pharmaceuticals; 2003 July Dicloxacillin sodium package insert. Toronto, Canada.; Novopharm Limited;2006 Jan Nitrofurantoin capsules package insert. Morgantown, Wv; Mylan Pharmaceuticals; 2004 August Amoxicillin and clavulanate potassium tablets package insert. Princeton,NJ; Sandoz Inc: 2007 June Clindamycin package insert. Sellersville, Pa; Teva Pharmaceuticals; 2004 Nov Neomycin and polymyxin B sulfates and hydrocortisone otic susp. USP package insert. Tampa, Fl; Bausch & Lomb Inc; 2003 Nov. Xifaxan package insert. Morrisville, NC; Salix Pharmaceuticals; 2008 March Davis F A, Taber’s Cyclopedic Medical Dictionary, 20th edition, 2005

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