[04.23] General Principles of Antimicrobial Therapy V2.pdf

700,000

According to an estimate, how many people around the world die each year because they have an infection that has become immune to the drugs used to treat it?

efficacy, safety, suitability, and cost (ESSC)

What four factors define rational drug use for antimicrobial choice?

Polymorphisms and genetic makeup of the host, State of being immunocompromised, Presence of comorbidities

Name three factors related to the host that must be considered when selecting an antimicrobial.

Spectrum of the antimicrobial action, Efficacy, safety, suitability, and cost (ESSC)

Name two factors related to the drug that must be considered when selecting an antimicrobial.

Whether the species is resistant species, Whether first-line antimicrobials can be used

Name two factors related to the microbe that must be considered when selecting an antimicrobial.

Narrowest spectrum, Least toxic to the host, Least likely cause resistance

What are the three goals of antimicrobial stewardship related to drug choice?

Stronger doses or a higher generation of antimicrobials

What might an immunocompromised state require regarding antimicrobial treatment?

Hepatic or renal clearance

What physiological process may be affected by the presence of comorbidities, influencing antimicrobial choice?

Improve the drug efficacy, safety, and suitability for each host

What is the benefit of knowing host factors in antimicrobial selection?

Altered drug disposition

What change in drug characteristics occurs during pregnancy that affects antimicrobial dose?

Increased intravascular volume, Increased glomerular filtration rate, Increased hepatic and metabolic activities

Name two physiological changes in pregnancy that alter drug disposition.

Higher dose

What adjustment in antimicrobial dosage may be required in pregnancy to produce a similar effect?

Penicillin, cephalosporins, and erythromycin

Name two antimicrobials that are generally safer to use during pregnancy.

Chloramphenicol, Quinolones, Trimethoprim-sulfamethoxazole

Name two antimicrobials that are contraindicated in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency.

Inter-individual variability and response

What is affected by genetic polymorphisms or metabolic abnormalities, such as G6PD deficiency, influencing antimicrobial choice?

Bug factors

What is another name for microbial factors considered in drug choice?

Community acquired infections

What type of infection may require basic antimicrobials?

Nosocomial infections

What type of infection may require a higher combination or a higher dose of antimicrobials?

Resistance and virulence factors

What microbial considerations can determine if a higher generation of antimicrobials is required?

Microbe load, Microbe ability to adhere, penetrate, and invade, Microbe mechanism of damage, Portal of exit

Name three factors that may determine the efficacy of a microbe when tracing its pathway from the portal of entry.

Endotoxin or exotoxin, Direct cytopathic effects or alterations in the metabolism of the host cell

Name two mechanisms of damage caused by microbes.

Upper Respiratory Tract, Skin, GI, Genitourinary tract

Name two sites where normal flora are found that are primary suspects for community acquired infections.

Gram negative organisms

What type of organism is a primary suspect for infections in hospital or long-term care facilities?

More virulent and invasive species

What characteristic makes Gram negative organisms primary suspects in hospital settings?

Advanced 2nd or 3rd generation antimicrobials

What level of antimicrobials do Gram negative organisms in hospital settings usually require?

They prevent harmful pathogens by competing for attachment sites

What is a protective role of normal flora?

They are the source of opportunistic infections when the host is immunocompromised

What role does normal flora play when the host's immune system is compromised?

They have internal functions (e.g., digestion of food)

What internal function is attributed to normal flora, such as Enterobacter and Enterococci?

Normal flora does not become invasive and cause disease

What specific action is excluded from the role of normal flora?

Provide resistance patterns within the locality

What information is provided by National Antibiotic Guidelines or other antibiogram evidence-based information?

Antibiograms from various hospitals

What are compiled in the National Antibiotic Guidelines to predict antimicrobial usage?

Mechanism of action, Spectrum of activity, Type of action

What are the three ways antimicrobials can be classified?

Whether they affect gram-positive or gram-negative organisms

What does the spectrum of activity of an antimicrobial describe?

Cell wall inhibitors, Plasma membrane disruptors, Protein synthesis inhibitors, Metabolic pathway inhibitors, DNA synthesis inhibitors

Name three major mechanisms by which different antimicrobial drugs work.

Beta-lactams, Extended spectrum penicillin, Carbapenems, Extended spectrum penicillin

Name three classes of antimicrobials sensitive to Gram-positive Cocci.

Quinolones, Gentamicin, Third generation cephalosporins, Moxifloxacin (third generation quinolone)

Name three classes of antimicrobials sensitive to Gram-negative Bacilli.

Clindamycin, Metronidazole, Extended spectrum penicillin, Carbapenems, Ertapenem

Name three classes of antimicrobials sensitive to Anaerobes.

Urgency of the need to control infection

What determines the classification of an antimicrobial as bactericidal or bacteriostatic?

Cell wall-active agents

What class of agents is generally considered bactericidal?

Drugs that inhibit protein synthesis

What class of drugs is generally considered bacteriostatic?

Immediate destruction of the cell

What action characterizes bactericidal drugs?

Beta-lactams

Name an example of a bactericidal drug that disrupts the cell wall causing immediate lysis and death.

Quinolones, rifampicin, and nitroimidazoles

Name two examples of bactericidal drugs that interfere with DNA synthesis.

Aminoglycosides, Bacitracin, Quinolones, Beta-lactam antibiotics, Carbapenems (imipenem and meropenem), Daptomycin, Rifampicin

Name three bactericidal drugs that affect microbes in the non-growing phase.

Gentamicin, Quinolones, Piperacillin, Cefotaxime

Name two bactericidal drugs that affect microbes when they are actively replicating (rapid growth phase).

Beta-lactams, Aminoglycosides, Nitroimidazoles (metronidazole), Glycopeptides (vancomycin), Quinolones, Rifampicin, Polymyxins (colistin)

Name three classes of bactericidal antibiotics using the BANG Q R.I.P mnemonic.

Inhibit the synthesis of proteins

What action characterizes bacteriostatic drugs?

Allow normal flora to destroy the bacteria over time

What is the secondary effect of bacteriostatic drugs that inhibit protein synthesis?

Macrolides

Which protein synthesis inhibitor acts by inhibiting the 50s ribosomal subunit?

Tetracyclines

Which protein synthesis inhibitor acts by inhibiting the 30s ribosomal subunit?

Chloramphenicol, Clindamycin, Macrolides, Oxazolidinones, Tetracyclines

Name three bacteriostatic drugs that inhibit protein synthesis (Bacteriostatic Protein Synthesis Inhibitors).

Sulfonamide, Trimethoprim

Name the two drugs classified as anti-metabolites (bacteriostatic).

Nitrofurantoin, Novobiocin, Ethambutol

Name two bacteriostatic drugs that belong to Drug Class B (later phase inhibition).

Macrolides, Sulfonamides, Chloramphenicol, Oxazolidinones, Lincosamides (clindamycin), Tetracyclines

Name three classes of bacteriostatic antibiotics using the MS. COLT mnemonic.

Small doses

At what concentration does Trimethoprim-sulfamethoxazole act as bacteriostatic?

High doses

At what concentration does Trimethoprim-sulfamethoxazole act as bactericidal?

Presumptive treatment

What type of treatment is Empiric antimicrobial therapy?

Anticipated and targeted at the likely cause of infection

What is the aim of empiric antimicrobial treatment?

Host, Microbe (bug), Drug considerations

What three principles guide empiric antimicrobial treatment?

Before a specific diagnostic can provide more information on the bacteria or fungus causing the infection

When is empiric antimicrobial treatment used?

Trimethoprim-sulfamethoxazole

What is contraindicated in G6PD deficiency, besides Chloramphenicol and Quinolones?

Doxycycline

Which drug is not a contraindication in G6PD deficiency among the options Quinolones, Trimethoprim-sulfamethoxazole, Doxycycline, and Chloramphenicol?

False

Is the statement "Beta-lactams are bacteriostatic antibiotics" true or false?

False

Is the statement "In classifying antimicrobials according to their mechanism of action, one looks at whether it affects gram positive or gram negative organisms" true or false?

Pneumonia

What is the most common HAI in public hospitals in the Philippines, accounting for 35% of cases?

Central-Line Associated Bloodstream Infections (CLABSIs)

What type of HAI accounts for 29% of cases in public hospitals in the Philippines, combining line-related and bloodstream infections?

Plotted antimicrobial concentration over time (Dose-Response Curve) superimposed with the control of microbial growth

What is a useful predictor of bactericidal activity?

Area under the curve (AUC)

What parameter on the dose-response curve represents the period in which the antimicrobial coverage can inhibit growth?

Minimum inhibitory concentration (MIC)

What parameter on the dose-response curve represents the minimum concentration by which the antimicrobial is capable of inhibiting growth in the culture?

Cmax

What parameter on the dose-response curve represents the maximal concentration achieved by the drug?

Time the concentration of the drug reaches MIC, Maximum time that it is above and in your Cmax, Finding out the AUC which is under the MIC

Name two parameters that determine the efficacy of some antimicrobials.

T > MIC

What is the parameter of interest for Time-Dependent Antimicrobial Strategy?

Maximum effect is achieved by exposing the microbes at a concentration of antimicrobial that is slightly above the MIC

How is maximum effect achieved in time-dependent killing?

At least 70% of the dosing interval

How long must the antimicrobial level be kept above the MIC for time-dependent killing to be effective?

Beta Lactams (Penicillin, Cephalosporins, Carbapenems, Meropenem, Ertapenem), Macrolides (Erythromycin), Oxazolidinones (Linezolid), Clindamycin

Name three drug classes that utilize a time-dependent kind of killing.

Faster rate

What is the rate of antimicrobial control in concentration-dependent killing compared to time-dependent killing?

Aminoglycosides, Fluoroquinolones, Ketolides, Metronidazole, Amphotericin B

Name three drugs that are concentration dependent.

Cmax

At what concentration should concentration-dependent drugs ideally be to achieve a faster and more extensive degree of killing?

Cmax / MIC ratio

What is the most important predictor of antimicrobial efficacy for concentration-dependent drugs?

24h-AUC/MIC ratio

What is the parameter that correlates with efficacy for antimicrobial drugs that have mixed time-dependent killing and maximal effects at higher concentrations?

Vancomycin, Azithromycin, Quinolones, Tetracyclines, Quinupristin, Dalfopristin

Name three drugs that have 24h-AUC/MIC properties.

Continued antibacterial activity after antibiotic is removed or antibiotic levels fall below the MIC

What is the definition of Post-Antibiotic Effect (PAE)?

Aminoglycosides, Fluoroquinolones, Tetracyclines, Clindamycin, Certain newer macrolides/ketolides, Rifampicin, Rifabutin

Name three drugs that characterize the Post-Antibiotic Effect.

Slow recovery after reversible nonlethal damage to cell structures, Persistence of the drug at a binding site or within the periplasmic space, The need to synthesize new enzymes before growth can resume

Name two reasons for the delayed time for bacteria to return to log growth during PAE.

Post antibiotic Leukocyte Enhancement (PALE)

What refers to the enhanced susceptibility of organisms to antibacterial activity after antibiotic exposure due to enhanced leukocyte function?

Intravenous preparations

Which route of administration is reserved for more critical patients or those who cannot tolerate oral absorption?

Less cost, Less invasive means

Name two advantages of oral preparations of antimicrobials?

Cerebrospinal Fluid (CSF) penetration

What specific distribution capability of an antimicrobial is significantly increased in inflamed meninges?

Trimethoprim, Sulfamethoxazole, Cefuroxime, Cefotaxime

Name two drugs that have high CSF penetrance in uninflamed meninges.

Cefuroxime, Cefotaxime, Ceftazidime

Name two drugs that have high CSF penetrance in inflamed meninges.

Chloramphenicol, Erythromycin, Clindamycin, Metronidazole

Name two drugs that require dose adjustment in cases of impaired hepatic metabolism.

Most beta-lactams, Trimethoprim/Sulfamethoxazole (TMS), Aminoglycosides, Tetracyclines

Name two drugs that require dose adjustment in cases of renal impairment.

Greater toxicity

What can excessive concentrations of drugs metabolized by the liver cause in cases of impaired hepatic metabolism?

Improvement in signs and symptoms, Fever curve, Decrease in WBC, Decrease in erythema, pain, cough, drainage, etc.

Name two clinical metrics used to evaluate clinical response for efficacy during antimicrobial monitoring.

Serum levels

What diagnostic is used to determine the peak and trough levels of antimicrobials?

Renal and/or hepatic function

What functions are monitored to check for hepatic or renal compromise?

Culture and sensitivity (C/S)

What microbiology report is used to determine susceptibility or resistance of the microorganism.

Incorrect diagnosis, Other comorbid conditions, Costs of medications, Inadequate dosing, Drug resistance, New infections (or nosocomial superinfections)

Name three factors that should be considered when evaluating non-response to antimicrobial therapy.

Interactions with other medications, Hypersensitivity reactions, Fetal damage/risk to pregnant women, Bone marrow suppression, Ototoxicity from aminoglycosides

Name three safety concerns of antimicrobials.

Penicillins

What drug group is frequently associated with hypersensitivity reactions?