Medications for Infectious Diseases in Advanced Pharmacology

What percentage of hospitalized patients are given antibiotics?

Nearly 30%.

What are some reasons why more antibiotics need to be developed?

Some microbes don't respond well to current antimicrobials, some antimicrobials are toxic, and some microbes have developed resistance.

What are the two types of bacterial resistance?

Innate and acquired.

What are the consequences of bacterial resistance?

It can render drugs useless and is associated with increased mortality and morbidity.

What are the four mechanisms of bacterial resistance?

1. Decrease drug concentration at the site of action. 2. Alter the structure of the drug's target molecule. 3. Produce a drug antagonist. 4. Cause drug inactivation.

How do microbes decrease the concentration of the drug at the site of action?

They can cease active uptake of the drug, increase active export of drugs, or have a barrier that prevents drugs from reaching surface receptors.

What is target modification in bacterial resistance?

The cell gradually changes the shape of the target molecule, affecting drug efficacy.

Give an example of target modification related to penicillin.

Penicillin-binding protein and penicillin in MRSA.

What is the role of competitors in bacterial resistance?

Microbes produce a molecule that competes with the medication, such as sulfonamides competing with PABA.

How do some bacteria inactivate drugs?

They produce enzymes that inactivate the drug, such as β-lactamase (penicillinase) inactivating penicillin.

What are the two primary ways resistance occurs through alteration of bacterial DNA?

1. Spontaneous mutation, which influences resistance to one drug. 2. Conjugation, which creates multi-drug resistance.

What is required for conjugation to create multi-drug resistance?

A DNA segment that codes for the mechanism of resistance and a DNA segment that codes for the transfer of DNA between bacteria, referred to as the R factor.

How does the use of antibiotics promote resistance?

Antibiotics kill sensitive microorganisms, allowing resistant strains to survive and thrive in the absence of competing organisms.

What are nosocomial infections?

Infections acquired in hospitals, often due to the overuse of antibiotics and invasive equipment.

What are some prevention strategies for nosocomial infections?

Remove Foley and IV catheters and practice handwashing.

What is a superinfection (suprainfection)?

A new infection that appears during the treatment of another infection, often caused by resistant organisms.

Why are superinfections more common with broad-spectrum antibiotics?

They eliminate sensitive organisms, allowing resistant organisms to flourish.

What are some clinical findings of a Candida infection?

Sore tongue, fuzzy tongue, vaginal itching or discharge, anal itching, and foul-smelling feces.

What is selective toxicity in pharmacology?

The ability of a drug to selectively target a harmful organism without injuring the host or other organisms.

How does selective toxicity occur?

It allows the drug to kill or suppress a harmful organism while sparing the host.

What biological differences exist between mammals and bacteria?

Mammals and bacteria have different biology, including the presence of a cell wall in bacteria and the ability of mammals to obtain folic acid from their environment.

What are two processes that antimicrobials target that are specific to bacteria?

1. Destruction of bacterial cell wall, which mammalian cells do not have. 2. Inhibition of a unique bacterial enzyme that synthesizes folic acid.

Why can bacteria not obtain folic acid from their environment?

Bacteria cannot obtain folic acid from the environment; they must synthesize it themselves.

How do bacterial ribosomes differ from mammalian ribosomes?

Bacterial ribosomes are structurally different from mammalian ribosomes, which is a target for antimicrobials.

What is the difference between broad spectrum and narrow spectrum antimicrobials?

Broad spectrum antimicrobials influence many microbes, while narrow spectrum antimicrobials influence only a few species of microbes.

What are the preferred types of antimicrobials and why?

Narrow spectrum antimicrobials are preferred because they target specific pathogens, minimizing harm to beneficial microbes.

What are some classifications of antimicrobials by mechanism of action?

1. Inhibit cell wall synthesis or activate enzymes that disrupt cell wall. 2. Increase cell membrane permeability. 3. Lethal inhibition of bacterial protein synthesis. 4. Non-lethal inhibition of bacterial protein synthesis. 5. Inhibit DNA or RNA synthesis or disrupt DNA function. 6. Antimetabolites.

What is the goal of correct antibiotic use?

To produce maximum effect with minimum harm.

What steps should be taken to ensure effective antibiotic treatment?

1. Identify the organism. 2. Identify the drug sensitivity of the organism.

What is the first step in the correct use of antibiotics?

Identification of the infecting organism.

What staining method is easy and can be done on any body fluid for identification?

Gram stain.

When is a culture necessary in the identification process?

When a small number of infecting organisms is present.

What is important to ensure when collecting a culture sample?

It should be collected in a manner that reduces contamination and should not be exposed to oxygen.

What does PCR stand for and what is its purpose?

Polymerase chain reaction; it identifies low titres of bacteria and viruses and is more accurate than gram stain.

What is the second step in the correct use of antibiotics?

Sensitivity testing after the organism is identified.

When is sensitivity testing necessary?

Only for organisms in which resistance is an issue.

What is the disk diffusion method used for?

To determine the degree of sensitivity of bacteria to antibiotics.

What does the size of the bacteria-free zone around the disk indicate?

The degree of sensitivity of the bacteria to the antibiotic.

What is serial dilution used for in antibiotic sensitivity testing?

To identify the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of antibiotics.

What does MIC stand for?

Minimum inhibitory concentration.

What does MBC stand for?

Minimum bactericidal concentration.

What does a culture and sensitivity report help identify?

The source, organism(s), severity of the infection, and sensitivity to various antibiotics.

What does a lower MIC number indicate?

A lower concentration needed to inhibit growth and greater sensitivity to the antibiotic.

What type of antibiotics are most commonly used and what do they do?

Most antibiotics are bacteriostatic, meaning they prevent the growth of bacteria.

Why are immunocompromised patients at increased risk with infections?

Due to poor host defenses, they require bactericidal antibiotics.

What is a concern regarding antibiotics and lactation?

Many antibiotics are expressed in breast milk, which can affect the infant.

What is a specific risk associated with Gentamycin in infants?

It can cause hearing loss.

What is a specific risk associated with Tetracyclines in infants?

It can stain infant teeth.

What is a challenge with certain sites of infection regarding antibiotic treatment?

Some sites are difficult to reach, requiring facilitation of antibiotic penetration.

What is empiric therapy?

The practice of administering an antibiotic based on knowledge of the most likely organism, especially in life-threatening situations.

What must be done before administering antibiotics in suspected infections?

Cultures of body fluids must be drawn.

What should be the initial choice of antibiotic for a UTI?

An antibiotic that targets E. coli.

What should be the initial choice of antibiotic for community-acquired pneumonia?

An antibiotic that targets Streptococcus.

What is prophylaxis in the context of antibiotics?

The use of antibiotics to prevent infection rather than treat it, with as many as 50% of antibiotics prescribed for this purpose.

What are some high-risk surgical procedures that may require antibiotic prophylaxis?

Procedures involving abdominal organs, emergency cesarean sections, compound fractures, and lacerations from animal bites.

Which patients are at high risk for endocarditis and may need prophylactic antibiotics during dental procedures?

Individuals with congenital heart defects or prosthetic heart valves.

What is a potential risk of prophylaxis in neutropenic patients?

While prophylaxis can reduce the risk of bacterial infection, it may increase the risk of fungal infection.

What is a common misuse of antibiotics in treating upper respiratory infections?

Upper respiratory infections are commonly caused by viruses, which are not susceptible to antibiotics.

What should be done if the cause of a fever of unknown origin is not identified?

Antibiotics should not be prescribed.

What is the most common reason children receive antibiotics?

Acute otitis media (AOM).

What are the common organisms that cause acute otitis media?

Streptococcus pneumoniae, Haemophilus influenza, and Moraxella catarrhalis.

What are the first-line treatments for acute otitis media?

1. Amoxicillin 2. Amoxicillin/clavulanate if no improvement with amoxicillin 3. Cephalosporin if there is a penicillin allergy.

What class of antibiotics weakens the bacterial cell wall?

Beta-lactam antibiotics, which include penicillins, cephalosporins, carbapenems, and monobactams.

What is the mechanism of action of penicillins?

Penicillins bind to penicillin binding proteins (PBPs) in the cell wall, inhibiting enzymes that synthesize cell walls and activating enzymes that break down the cell wall.

What are some reasons for bacterial resistance to penicillins?

1. Decreased concentration due to thick outer membranes of some gram-negative bacteria. 2. Enzymatic action from beta-lactamase that destroys the beta-lactam ring. 3. Alteration of target molecules, such as in MRSA.

What is β-lactamase, also known as penicillinase?

An enzyme produced by some bacteria that destroys the beta-lactam ring of penicillins.

What is the most common adverse effect associated with penicillins?

Allergic reactions, ranging from rash to anaphylaxis.

What should patients with a penicillin allergy be cautious of?

Cross sensitivity to cephalosporins, which are related to penicillins.

What is the treatment for severe allergic reactions to penicillins?

Epinephrine (1:1000 concentration IM) is used for anaphylaxis.

What should patients with a history of severe penicillin allergy do?

Wear a Medi-alert bracelet and consider desensitization if penicillin is necessary for life-threatening infections.

What are the characteristics of penicillins in terms of spectrum and toxicity?

Some penicillins are narrow-spectrum with low toxicity, while others are broad-spectrum or extended-spectrum.

What is the role of autolysins in the action of penicillins?

Autolysins are activated enzymes that break down the cell wall, contributing to bacterial lysis.

What are the implications of using broad-spectrum antibiotics like vancomycin?

There is a need to identify the organism and obtain susceptibility information to avoid misuse.

What is the significance of penicillin binding proteins (PBPs)?

PBPs are targets for penicillins, and their alteration can lead to resistance.

What is the risk associated with overprescribing antibiotics?

Overprescribing can lead to antibiotic resistance and unnecessary side effects.

What is a common side effect at the injection site for beta-lactam antibiotics?

Pain at injection site.

What is the spectrum of activity for Penicillin G?

Narrow spectrum.

What are two key characteristics of Penicillin G?

It tends to be very safe and is unstable in stomach acid, thus cannot be given orally.

What is the primary advantage of Penicillin V over Penicillin G?

Penicillin V is stable in stomach acid and can be given orally.

How do the absorption rates of penicillins vary when given intramuscularly (IM)?

All penicillins can be given IM but vary in absorption; for example, Benzathine Penicillin G is absorbed slowly over weeks.

What are two examples of broad spectrum penicillins?

Amoxicillin and Ampicillin.

What additional side effect is associated with broad spectrum penicillins?

Diarrhea.

What is an example of an extended spectrum penicillin and its effectiveness?

Piperacillin, which is effective against Pseudomonas.

How do beta-lactamase inhibitors work?

They are structurally similar to beta-lactam antibiotics and prevent the destruction of the beta-lactam ring by binding to beta-lactamase.

Name three combinations of penicillins with beta-lactamase inhibitors.

Ampicillin/sulbactam (Unasyn), Amoxicillin/clavulanate (Augmentin), Piperacillin/tazobactam (Zosyn).

What are cephalosporins and how do they relate to penicillins?

Cephalosporins are similar in structure and action to penicillins; they are bactericidal and contain a beta-lactam ring.

What increases from the first to the fifth generation of cephalosporins?

Activity against gram-negative bacteria, ability to resist beta-lactamase, and ability to cross the blood-brain barrier (BBB).

What is an example of a first-generation cephalosporin?

Cephalexin (Keflex).

What is a notable characteristic of fifth-generation cephalosporins?

Ceftaroline (Teflaro) is the only cephalosporin with activity against MRSA.

What is the mechanism of action for cephalosporins?

They bind to PBPs in the cell wall, inhibit enzymes that synthesize the cell wall, and activate enzymes that break down the cell wall, resulting in lysis of the cell.

What is a common adverse effect associated with cephalosporins?

Allergic reactions, usually in the form of a rash.

What is a significant interaction to be aware of with cephalosporins?

Alcohol can cause a disulfiram reaction with several cephalosporins.

What are carbapenems and their spectrum of activity?

Carbapenems are beta-lactam antibiotics with a very broad spectrum and are resistant to beta-lactamase.

What is the primary route of administration for carbapenems?

They must be given IV as they are not absorbed from the GI tract.

What is the mechanism of action for carbapenems?

They bind to PBPs, weaken the cell wall, and cause lysis, making them bactericidal.

What is the only monobactam in use and its spectrum of activity?

Aztreonam (Azactam), which has a very narrow spectrum and is only effective against gram-negative aerobes.

What are common adverse effects of Aztreonam?

Pain at the injection site and thrombophlebitis at the IV site.

What is vancomycin primarily used to treat?

Clostridium difficile infections and MRSA.

What type of bacteria is vancomycin active against?

Only against gram-positive bacteria.

What is a key structural feature of vancomycin?

It does not contain a beta-lactam ring.