1、Anti infective agentsChapters 37,38,39&41Antibiotics:DefinitionnMedications used to treat bacterial infectionsnIdeally,before beginning antibiotic therapy,the suspected areas of infection should be cultured to identify the causative organism and potential antibiotic susceptibilitiesAntibiotics:Class
2、esn Sulfonamidesn Penicillinsn Cephalosporinsn Tetracyclinesn MacrolidesnAminoglycosidesnQuinolonesFigure 37-1 Bacterial morphologies.(From Murray,P.R.,Rosenthal,K.S.,Kobayashi,G.S.,&Pfaller,M.A.(2002).Medical microbiology.St.Louis,MO:Mosby.)Figure 37-3 Gram-stain morphology of bacteria.The crystal
3、violet of Gram stain is precipitated by Gram iodine and is trapped in the thick peptidoglycan layer in gram-positive bacteria.The decolorizer disperses the gram-negative outer membrane and washes the crystal violet from the thin layer of peptidoglycan.Gram-negative bacteria are visualized by the red
4、 counterstain.(From Murray,P.R.,Rosenthal,K.S.,Kobayashi,G.S.,&Pfaller,M.A.(2002).Medical microbiology.St.Louis,MO:Mosby.)Figure 37-4 Gram-positive and gram-negative bacteria.A gram-positive bacterium has a thick layer of peptidoglycan(left).A gram-negative bacterium has a thin peptidoglycan layer a
5、nd an outer membrane(right).Structures in parentheses are not found in all bacteria.(From Murray,P.R.,Rosenthal,K.S.,Kobayashi,G.S.,&Pfaller,M.A.(2002).Medical microbiology.St.Louis,MO:Mosby.)Antibiotic TherapynEmpiric therapy:treatment of an infection before specific culture information has been re
6、ported or obtainednProphylactic therapy:treatment with antibiotics to prevent an infection,as in intraabdominal surgeryAntibiotic Therapy(contd)nTherapeutic response Decrease in specific signs and symptoms of infection are noted(fever,elevated WBC,redness,inflammation,drainage,pain)nSubtherapeutic r
7、esponse Signs and symptoms of infection do not improveAntibiotic Therapy(contd)Four common mechanisms of actionnInterference with cell wall synthesisnInterference with protein synthesisnInterference with DNA replicationnActing as a metabolite to disrupt critical metabolic reactions inside the bacter
8、ial cellActions of AntibioticsnBactericidal:kill bacterianBacteriostatic:inhibit growth of susceptible bacteria,rather than killing them immediately;will eventually lead to bacterial deathAntibiotics:SulfonamidesOne of the first groups of antibioticsnsulfadiazinenSulfamethoxazole(Bactrim)nsulfisoxaz
9、oleSulfonamides:Mechanism of ActionnBacteriostatic actionnPrevent synthesis of folic acid required for synthesis of purines and nucleic acidnDo not affect human cells or certain bacteriathey can use preformed folic acidSulfonamides:IndicationsnTreatment of UTIs caused by susceptible strains of:Enter
10、obacter spp.,Escherichia coli,Klebsiella spp.,Proteus mirabilis,Proteus vulgaris,Staphylococcus aureusnNocardiosisnPneumocystis carinii pneumonia(PCP)nUpper respiratory tract infectionsnOther usesSulfonamides:Combination Productsntrimethoprim/sulfamethoxazole Used to treat UTIs,PCP,otitis media,othe
11、r conditionsnerythromycin/sulfisoxazole Used to treat otitis mediansulfisoxazole Used to treat otitis media,UTIs,other conditionsBeta-Lactam AntibioticsnPenicillinsnCephalosporinsnCarbapenemsnMonobactamsPenicillinsnNatural penicillinsnPenicillinase-resistant penicillinsnAminopenicillinsnExtended-spe
12、ctrum penicillinsPenicillins(contd)Natural penicillinsnpenicillin G,penicillin V potassiumPenicillinase-resistant penicillinsnCloxacillinAminopenicillinsnamoxicillin,ampicillin,pivamicillinAnti-pseudomonal penicillins npiperacillin sodium Penicillins(contd)nFirst introduced in the 1940snBactericidal
13、:inhibit cell wall synthesisnKill a wide variety of bacterianAlso called“beta-lactams”Penicillins(contd)nBacteria produce enzymes capable of destroying penicillinsnThese enzymes are known as beta-lactamasesnAs a result,the medication is not effectivePenicillins(contd)nChemicals have been developed t
14、o inhibit these enzymes:Clavulanic acid(Clavulin)Tazobactam SulbactamnThese chemicals bind with beta-lactamase and prevent the enzyme from breaking down the penicillinPenicillins:Mechanism of ActionnPenicillins enter the bacteria via the cell wallnInside the cell they bind to penicillin-binding prot
15、einnOnce bound,normal cell wall synthesis is disruptednResult:bacteria cells die from cell lysisnPenicillins do not kill other cells in the bodyPenicillins:IndicationsnPrevention and treatment of infections caused by susceptible bacteria,such as:Gram-positive bacteria Streptococcus,Enterococcus,Stap
16、hylococcus spp.Penicillins:Adverse EffectsnAllergic reactions occur in 0.7%to 8%of cases Urticaria,pruritus,angioedeman10%of allergic reactions are life threatening 10%of these are fatalPenicillins:Side EffectsnCommon side effects Nausea,vomiting,diarrhea,abdominal painnOther side effects are less c
17、ommonCephalosporinsnFirst generationnSecond generationnThird generationnFourth generationCephalosporins(contd)nSemisynthetic derivatives from a fungusnStructurally and pharmacologically related to penicillinsnBactericidal actionnBroad spectrumnDivided into groups according to their antimicrobial act
18、ivityCephalosporins:First Generationncephalexin(Keflex)ncefazolin(Ancef)ncefadroxil(Duricef)nGood gram-positive coveragenPoor gram-negative coverageCephalosporins:First Generation(contd)nUsed for surgical prophylaxis,URIs,otitis media cefazoline:IV or PO(Ancef)cephalexin:PO(Keflex)Cephalosporins:Sec
19、ond GenerationnGood gram-positive coveragenBetter gram-negative coverage than first generation cefaclor cefprozil cefoxitin cefuroxime cefotetanCephalosporins:Second Generation(contd)ncefoxitin:IV and IM Used prophylactically for abdominal or colorectal surgeries Also kills anaerobesncefuroxime:PO S
20、urgical prophylaxis Does not kill anaerobesCephalosporins:Third GenerationnMost potent group against gram-negativenLess active against gram-positive cefixime cefotaxime ceftizoxime ceftriaxone ceftazidimeCephalosporins:Third Generation(contd)cefixime nOnly oral third-generation agentnBest of availab
21、le oral cephalosporins against gram-negativenTablet and suspensionceftriaxone nIV and IM,long half-life,once-a-day administrationnEasily passes meninges and diffused into CSF to treat CNS infectionsCephalosporins:Fourth Generationncefepime Newest cephalosporin agents Broader spectrum of antibacteria
22、l activity than third generation,especially against gram-positive bacteriaCephalosporins:Side EffectsSimilar to penicillins MacrolidesnerythromycinnazithromycinnclarithromycinMacrolides:Mechanism of ActionnPrevent protein synthesis within bacterial cellsnBacteria will eventually dieMacrolides:Indica
23、tionsnStrep infections Streptococcus pyogenes(group A beta-hemolytic streptococci)nMild to moderate URI Haemophilus influenzaenSpirochetal infections Syphilis and Lyme diseasenGonorrhea,Chlamydia,MycoplasmaMacrolides:Side EffectsGI effects,primarily with erythromycinnNausea,vomiting,diarrhea,hepatot
24、oxicity,flatulence,jaundice,anorexianNewer agents,azithromycin and clarithromycin:fewer side effects,longer duration of action,better efficacy,better tissue penetrationTetracyclinesndemeclocycline noxytetracyclinentetracyclinendoxycycline nminocyclineTetracyclines(contd)nNatural and semisyntheticnOb
25、tained from cultures of StreptomycesnBacteriostaticinhibit bacterial growthnInhibit protein synthesisnStop many essential functions of the bacteriaTetracyclines(contd)nBind to Ca2+and Mg2+and Al3+ions to form insoluble complexesnThus,dairy products,antacids,and iron salts reduce absorption of tetrac
26、yclinesTetracyclines:IndicationsnWide spectrum Gram-negative,gram-positive,protozoa,Mycoplasma,Rickettsia,Chlamydia,syphilis,Lyme diseasendemeclocycline is also used to treat SIADH,and pleural and pericardial effusionsTetracyclines:Side EffectsStrong affinity for calcium nDiscoloration of permanent
27、teeth and tooth enamel in fetuses and childrennMay retard fetal skeletal development if taken during pregnancyTetracyclines:Side Effects(contd)Alteration in intestinal flora may result in:nSuperinfection(overgrowth of nonsusceptible organisms such as Candida)nDiarrheanPseudomembranous colitisTetracy
28、clines:Side Effects(contd)May also cause:nVaginal moniliasisnGastric upsetnEnterocolitisnMaculopapular rashAminoglycosidesngentamicin nneomycinnstreptomycinntobramycinnamikacin Aminoglycosides(contd)nNatural and semisyntheticnProduced from StreptomycesnPoor oral absorption;no PO formsnPotent antibio
29、tics with serious toxicitiesnBactericidal;prevents protein synthesisnKill mostly gram-negative;some gram-positive alsoAminoglycosides:IndicationsnUsed to kill gram-negative bacteria such as Pseudomonas spp.,E.coli,Proteus spp.,Klebsiella spp.,Serratia spp.nOften used in combination with other antibi
30、otics for synergistic effectAminoglycosides:Indications(contd)nAll aminoglycosides are poorly absorbed through the GI tract,and given parenterallynException:neomycin Given orally to decontaminate the GI tract before surgical procedures Also used as an enema for this purposeAminoglycosides:AgentsnThr
31、ee most common(systemic):gentamicin,tobramycin,amikacinnCause serious toxicities Nephrotoxicity(renal failure)Ototoxicity(auditory impairment and vestibular eighth cranial nerve)nMust monitor drug levels to prevent toxicitiesAminoglycosides:Side EffectsnOtotoxicity and nephrotoxicity are the most si
32、gnificant Headache Paresthesia Neuromuscular blockade Dizziness Vertigo Skin rash Fever SuperinfectionsQuinolonesnciprofloxacin nnorfloxacin nofloxacin nlevofloxacin ngatifloxacin Quinolones(contd)nExcellent oral absorptionnAbsorption reduced by antacidsnFirst oral antibiotics effective against gram
33、-negative bacteriaQuinolones:Mechanism of ActionnBactericidalnEffective against gram-negative organisms and some gram-positive organismsnAlter DNA of bacteria,causing deathnDo not affect human DNAQuinolones:IndicationsnLower respiratory tract infectionsnBone and joint infectionsnInfectious diarrhean
34、Urinary tract infectionsnSkin infectionsnSexually transmitted diseasesnAnthraxQuinolones:IndicationsnLower respiratory tract infectionsnBone and joint infectionsnInfectious diarrheanUrinary tract infectionsnSkin infectionsnSexually transmitted diseasesnAnthraxQuinolones:Side EffectsBody SystemEffect
35、sCNSHeadache,dizziness,fatigue,depression,restlessnessGINausea,vomiting,diarrhea,constipation,thrush,increased liver functionstudiesQuinolones:Side Effects(contd)Body SystemEffectsIntegumentaryRash,pruritus,urticaria,flushing,photosensitivity(with lomefloxacin)OtherFever,chills,blurred vision,tinnit
36、usOther Antibioticsnclindamycin(MRSA)nMetronidazole(anaerobes)nnitrofurantoin(uncomplicated UTI)Other Antibiotics(contd)nvancomycin Natural,bactericidal antibiotic Destroys cell wall Treatment of choice for MRSA,and other gram-positive infections Must monitor blood levels to ensure therapeutic level
37、s and prevent toxicity May cause ototoxicity and nephrotoxicityOther Antibiotics(contd)nvancomycin(contd)Should be infused over 60 minutes Monitor IV site closely Redmans syndrome may occur Decreased BP,flushing of neck and face Antihistamine may be ordered to reduce these effects Ensure adequate hy
38、dration(2 L fluids/24 hr)if not contraindicated to prevent nephrotoxicityAntibiotics:Nursing ImplicationsnBefore beginning therapy,assess drug allergies;hepatic,liver,and cardiac function;and other lab studiesnBe sure to obtain thorough client health history,including immune statusnAssess for condit
39、ions that may be contraindications to antibiotic use or that may indicate cautious usenAssess for potential drug interactionsNursing ImplicationsIt is recommended to obtain cultures from appropriate sites BEFORE beginning antibiotic therapyNursing Implications(contd)nClients should be instructed to
40、take antibiotics exactly as prescribed and for the length of time prescribed;they should not stop taking the medication early when they feel betternAssess for signs and symptoms of superinfection:fever,perineal itching,cough,lethargy,or any unusual dischargeNursing Implications(contd)For safety reas
41、ons,check the name of the medication carefully because there are many agents that sound alike or have similar spellings Nursing Implications(contd)nEach class of antibiotics has specific side effects and drug interactions that must be carefully assessed and monitorednThe most common side effects of
42、antibiotics are nausea,vomiting,and diarrheanAll oral antibiotics are absorbed better if taken with at least 180 to 240 mL of water Nursing Implications(contd)nEach class of antibiotics has specific side effects and drug interactions that must be carefully assessed and monitorednThe most common side
43、 effects of antibiotics are nausea,vomiting,and diarrheanAll oral antibiotics are absorbed better if taken with at least 180 to 240 mL of water Nursing Implications(contd)nEach class of antibiotics has specific side effects and drug interactions that must be carefully assessed and monitorednThe most
44、 common side effects of antibiotics are nausea,vomiting,and diarrheanAll oral antibiotics are absorbed better if taken with at least 180 to 240 mL of waterNursing Implications(contd)SulfonamidesnShould be taken with at least 2000 mL of fluid per day,unless contraindicatednDue to photosensitivity,avo
45、id sunlight and tanning bedsnThese agents reduce the effectiveness of oral contraceptivesnOral forms should be taken with food or milk to reduce GI upsetNursing Implications(contd)PenicillinsnAny client taking a penicillin should be carefully monitored for an allergic reaction for at least 30 minute
46、s after its administrationnThe effectiveness of oral penicillins is decreased when taken with caffeine,citrus fruit,cola beverages,fruit juices,or tomato juiceNursing Implications(contd)CephalosporinsnOrally administered forms should be given with food to decrease GI upset,even though this will dela
47、y absorptionnSome of these agents may cause a disulfiram-like reaction when taken with alcoholNursing Implications(contd)MacrolidesnThese agents are highly protein-bound and will cause severe interactions with other protein-bound drugsnThe absorption of oral erythromycin is enhanced when taken on an
48、 empty stomach,but because of the high incidence of GI upset,many agents are taken after a meal or snackNursing Implications(contd)TetracyclinesnMilk products,iron preparations,antacids,and other dairy products should be avoided because of the chelation and drug-binding that occursnAll medications s
49、hould be taken with 180 to 240 mL of fluid,preferably waternDue to photosensitivity,avoid sunlight and tanning bedsNursing Implications(contd)AminoglycosidesnMonitor peak and trough blood levels of these agents to prevent nephrotoxicity and ototoxicitynSymptoms of ototoxicity include dizziness,tinni
50、tus,and hearing lossnSymptoms of nephrotoxicity include urinary casts,proteinuria,and increased BUN and serum creatinine levelsNursing Implications(contd)QuinolonesnShould be taken with at least 3 L of fluid per day,unless otherwise specifiednIntake of alkaline foods and drugs,such as antacids,dairy
