patcharasarn linasmita mdmed.swu.ac.th/internalmed/images/documents/lectures/id/...patients able to...
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Patcharasarn Linasmita MDInfectious Diseases Unit
Department of Medicine Faculty of Medicine
Srinakharinwirot University
Rational based on facts or reason and not on emotions
or feelings having the ability to reason or think about
things clearly
Patients receive medications appropriate to their clinical needs, in doses that meet their own individual
requirements, for an adequate period of time, and at the lowest cost to them and their
community. (WHO, 1985)
Morbidity / mortality / adverse reaction Stimulate inappropriate patient demand Waste of resources Medicine stock-out Increased treatment cost Loss of patient confidence in the health
system
The most important weapons for the treatment of many infectious diseases caused by bacteria.
Interference with patient’s normal flora Selection of drug resistant organisms
People often have very rational reasons for using
medicines irrationally.
Pressure/complaint from patient Peer pressure Cost saving??? (omit diagnostic test) Inappropriate promotion Profit motives
Lack of knowledge, skills Lack of independent information Unrestricted availability of antibiotics Overwork of health personnel
Patients receive medications appropriate to their clinical needs, in doses that meet their own individual
requirements, for an adequate period of time, and at the lowest cost to them and their
community. (WHO, 1985)
Rational thinking
Virus + no pathogen identified ~ 80% Group A Streptococcus + (Gr C, G) ~ 15%
▪ No evidence of beta-lactam resistance Other bacterial pathogens ~5%
▪ Chlamydophila pneumoniae▪ Mycoplasma pneumoniae▪ Arcanobacterium haemolyticum▪ Corynebactrium diphtheriae▪ Fusobacterium necrophorum▪ Neisseria gonorrheae▪ Treponema pallidum▪ Francisella tularensis
For diagnosis of Group A Streptococcal infection History of fever Tonsillar exudates Tender anterior cervical adenopathy Absence of cough
Presence of all 4 variable -> PPV 40-60%Absence of all 4 variables -> NPV > 80%
Hospital antibiotic policies National antibiotic policies Essential drug list Guidelines
http://newsser.fda.moph.go.th/rumthai/
Bacterial toxin Vomit No ATB
Annual Epidemiological Surveillance Report 2007
Diarrhea: 1,433,230 cases Dysentery: 19,026 cases (1.3%)
Shigella 0.3%
Prescribe ATB only if
▪ Fever
▪ Bloody diarrhea / RBC, WBC in stool exam
▪ Beware of EHEC O157:H7 ▪ HUS
▪ No ATB
ATB choice▪ norfloxacin
2 days of ATB prophylaxis
http://newsser.fda.moph.go.th/rumthai/userfiledownload/asu15dl.pdf
Community settings In-Hospital settings
Use of antibiotics to treat
▪ Non-infectious disease
▪ Antibiotic-unresponsive infectious disease
▪ Virus
▪ Fungus
▪ Bacterial colonization
Use of antibioitcs for persistent fevers.
Suboptimal empirical therapy Inappropriate combination therapy Dosing and duration errors Mismanagement of antibiotic failure
▪ Persistent fever
▪ Clinical failure.
Prophylaxis Empiric Specific
Obvious bacterial infection?
▪ Characteristic clinical findings
Urgent?
▪ Non urgent situation
▪ Subacute bacterial endocarditis
▪ Chronic osteomyelitis
▪ Urgent
▪ Acute endocarditis
▪ Meningitis.
Have appropriate clinical specimens been obtained?
▪ Staining
▪ Culture
Which organisms are most likely
▪ Type of focal infection
▪ Community vs nosocomial
▪ Prior colonization.
3 main factors Etiologic agents Antibiotic-related factors Patient-related factors
Indentification of the infecting organism
▪ Staining
▪ Culture; aerobe, anaerobe,
Determination of susceptibility
▪ Method?
▪ Local data?
▪ Antibiogram.
Infect Dis Clin N Am 1995;9:483–95.
Conc > MBC
MBC > Conc > MIC
Persistent antimicrobial effect
Regrowth!!
Adequate host defense?
Concentration-Dependent + Bactericidal Action + Prolonged PAE
▪ eg aminoglycoside
Time-Dependent + Bactericidal Action
▪ eg betalactam
Bacteriostatic + moderate to prolonged PAE▪ eg azithromycin
Host factors
▪ Previous allergic reaction?
▪ Age
▪ Genetic; G6PD deficiency, hemoglobinopathy?
▪ Sulfonimide, dapsone
▪ Pregnancy
▪ Renal and hepatic function
▪ Site of infection.
Which agent?
▪ Choice of the Proper Antibiotics
Combination?
▪ Different mechanisms.
Most infections in immunocompetent hosts can be treated with a single agent.
Combinations may provide broad-spectrum coverage than single agent can
Disadvantage Antagonism Cost Adverse reaction
▪ Which one? .
Initial therapy / empirical treatment
▪ High rate of resistance
▪ At least one of the agents would be active
▪ Often possible to switch to a single drug
Polymicrobial infections Prevention of the emergence of resistance
organism
▪ For P. aeruginosa -> controversy.
Antimicrobial synergism
▪ Endocarditis
▪ Enterococcal
▪ Prosthetic valve
▪ Prosthesis infection? .
Which agent?
▪ Choice of the Proper Antibiotics
Combination?
▪ Different mechanisms
How to assess effectiveness?
▪ Clinically
▪ Bacteriologically
Treatment modification.
Clinical worsening? Clinical improvement?
▪ De-escalation
▪ What if culture positive for MDR organism? .
Adequate? -> adequate coverage of resistance pathogen(s)
▪ Broad spectrum agent?
Appropriate?
▪ Agent
▪ Dosing and interval
▪ Tissue penetration
▪ Drug interaction.
Principles Use broad spectrum early
▪ Consider clinical context/setting
▪ Local susceptibility patterns
▪ Hx of colonization with resistant organism?
Optimize dose and duration De-escalation/streamlining.
Skin and soft tissue infections
▪ Including diabetic foot
Community-acquired pneumonia
▪ Caution in severe CAP
Community onset intraabdominal infection Community-acquired bacterial meningitis.
Adapted from Paterson DL. CID 2008; 47(S1): S14
Hospital acquired pneumonia (HAP/VAP) Fever in neutropenic patients Fever in critically ill patients.
Glycopeptide
▪ Vancomycin
▪ Teicoplanin
▪ Telavancin
Daptomycin Linezolid Tigecycline Streptogramin
Fusidic acid TMP/SMX Clindamycin Rifampin Fosfomycin Ceftobiprol.
Slow bacterial killing Poor tissue penetration Rising MICs for MRSA Inadequate dosing.
Suspected catheter infection History of known colonization of MRSA or
other penicillin/cephalosporin resistance gram positive pathogen
▪ Discontinue if cultures negative for these pathogens after 3-4 days
Gram positive lab data?
▪ Consider clinical setting.
VSSA MIC < 2 mg/L VISA MIC 4-8 mg/L VRSA MIC > 16 mg/L hVISA MIC 1-4 mg/L
▪ Subpopulation MIC > 4 mg/L > 1 in 106CFU /ml
*Disk testing is not reliable*
An AUC/MIC ratio of ≥400 has been advocated as a target to achieve clinical effectiveness with vancomycin.
Am J Health-Syst Pharm. 2009; 66:82-98
Minimum serum trough concentrations should always be maintained above 10 mg/L
▪ To avoid development of resistance
To generate the target AUC:MIC of 400 the minimum trough have to be at least 15 mg/L
▪ For pathogen with an MIC of 1 mg/L
Trough should be obtained just prior to the next dose at steady-state condition
▪ Just before the forth dose.
Am J Health-Syst Pharm. 2009; 66:82-98
Extended spectrum beta-lactamase
▪ E. coli, K. pneumoniae, K. oxytoca, Proteus mirabilis
Capable to hydrolize
▪ All penicillins
▪ All cephalosporins
▪ All monobactam
Cefoxitin is stable to this enzyme Inhibited by clavulanic acid.
Risk factors Prior hospitalization Prior antibiotics use
▪ 3rd generation chephalosporin
▪ Quinolone
Prior colonization Prolonged hospitalization.
Carbapenems -> most reliable Fluoroquinolones Tigecycline Aminoglycosides Colistin.
Serratia Pseudomonas Indole-positive Proteus Citrobacter Enterobacter Morganella Acinetobacter Providentia.
Strong inducer (and substrate)
▪ Benzylpenicillin, ampicillin, cefazolin
Strong inducer (stable for hydrolysis)
▪ Imipenem
Intermediate inducer (stable for hydrolysis)
▪ Meropenem
Weak inducer (and substrate)
▪ 3rd generation cephalosporin, piperacillin
Weak inducer (more stable)
▪ cefepime.
Serratia Pseudomonas Indole-positive Proteus Citrobacter Enterobacter Morganella Acinetobacter Providentia
Avoid 3rd generation cephalosporin
Choice: Quinolones,
carbapenems cefepime.
Pleomorphic gram negative coccobacilli Multidrug resistance Local data
▪ Prevalence/indidence
▪ Choice of antibiotic
▪ Sulbactam containing drug
▪ Tigecycline
▪ colistin.
Urinary tract infection/pyelonephritis
▪ Cefoperazone?
▪ Moxifloxacin?
Prostatitis
▪ Quinolones
▪ TMP/SMX.
Central Nervous System
▪ Beta-lactam/Beta-lactamase inhibitor?
▪ Amoxicillin/Ampicillin
▪ Piperacillin?
▪ Clavulanate/Sulbactam/Tazobactam?
▪ Aminoglycoside?
▪ Clindamycin?
▪ Colistin?
▪ Tigecycline? .
Hepatobiliary▪ Ciprofloxacin
▪ Piperacillin
▪ Ampicillin Lung/pneumonia
▪ Daptomycin?▪ Inhibited by pulmonary surfactant
Bone and Joint▪ Tigecycline?▪ Low concentration in bone .
Intracellular pathogen?
▪ Salmonella
▪ Legionella.
Only antibiotic? Other measures?
▪ Abscess -> drainage
▪ Foreign body
▪ Prosthetic joint
▪ Shunt
▪ Intravenous line.
Avoid
ESBLs
▪ Cefoxitin?
AmpC
▪ 3rd gen Cephalosporin? .
Staphylococcus aureus Resist to erythromycin Susceptible to clindamycin? erm gene? .
erm gene (erythromycin ribosomal methylase)
Inducible clindamycin resistance
Stenotrophomonas and carbapenems Enterococcus and cephalosporin
It is not effective against Pseudomonas aeruginosa Providencia sp Morganella morganii Proteus sp.
Proteus Providencia Serratia Edwardsiella Neisseria Moraxella catarrhalis Helicobacter pylori Brucella Chryseobacterium
indologenes
Burkholderia cepacia Elizabethkingia
meningoseptica Some strains of
Stenotrophomonas maltophilia
Aeromonas Vibrio Prevotella Fusobacterium.
Rather than route of administration, it’s more important to think in terms of
▪ Antibiotic spectrum
▪ Bioavailability
▪ Tissue penetration
Risk of nosocomial infection
▪ Septic phelebitis.
Patients able to take oral medications should be swith to PO equivalence therapy, unless
▪ critically ill
▪ Endocarditis
▪ Staphylococcus aureus bacteremia
Doxycyline, metronidazole, amoxicillin, TMP/SMX, levofloxacin, linezolid
▪ Food-drug interaction.
Interaction with quinolones and doxycycline
▪ magnesium or aluminum antacids
▪ sucralfate
▪ products containing calcium, iron, or zinc
Subtherapeutic antibiotic level.
Present with prolonged fever / FUO
▪ Infectious
▪ Non infectious
▪ Connective tissue disease
▪ Malignancy
Fever despite antibiotics
▪ Drug fever?
▪ Undrained source?
▪ Wrong dose? .
Drugs Factitious
▪ Healthcare personel Disorder heat
hemostasis▪ CNS
Hematoma Blood transfusion Endocrine:
▪ Hyperthyroidism,
▪ Adrenal insuffciency
▪ Pheochromocytoma
Atrial myxoma Cyclic neutropenia Gout Pulmonary embolism Tissue infarction Habitual hyperthermia
▪ Exaggerated circadian rhytm.
Only antibiotic? Other measures?
▪ Abscess -> drainage
▪ Foreign body
▪ Prosthetic joint
▪ Shunt
▪ Intravenous line.
Overuse and misuse of antibiotics have favored the growth of resistance organisms
It’s more important to reassess the patient than to add additional antibiotics.