Physiology- Bacterial Resistance

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Children and Antibiotics

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*highest rates of antibiotic use.
*highest rate of infections caused by antibiotic-resistant pathogens.

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Parent pressure makes a difference.

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For pediatric care, a recent study showed that doctors prescribe antibiotics 65% of the time if they perceive parents expect them; and 12% of the time if they feel parents do not expect them.

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Four Mechanisms of Antibacterial Action

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1) inhibition of DNA synthesis or function
2) inhibition of protein synthesis
3) inhibition of synthesis of microbial cell wall
4) lesion or destruction of mircobial membranes.

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Four Mechanism of Antimicrobial Resistance

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1) alteration of antibiotic targets
2) defects of antibiotic penetration
3) antibiotic inactivation by microbial enzymes
4) antibiotic excrusion/efflux

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Alteration of Antibiotic Targets

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Seen in Streptococcus pneumoniae and beta-lactam antibiotics

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Defects of Antibiotic Penetration

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E.coli towards hydrophobic antibiotics (penicillins G and M, macrolides)

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Antibiotic Inactivation by Microbial Enzymes

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Haemophilus influenzae, which produces beta-lactamase taht inactivate beta-lactam antibiotics

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Antibiotic Excrusion/Efflux

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E.coli, Staphlyococcus aureus, Pseudomonas aeruginosa towards cyclines and fluoroquinolones.

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Natural Resistance

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resistance is a characteristic of bacterial species.

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Most Frequent Mechanisms Involved in Natural Resistance

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1)Defect of antibiotic diffusion into the bacteria
2)Antibiotic inactivation by bacterial enzymes
3)Defect of affinity between bacterial target and antibiotics

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Acquired Resistance

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From either mutations on the chromosome or aquistion of foreign genes

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Three Mechanisms of Quinolone Resistance in Gram-negative Bacteria

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1) target alteration
2) active efflux
3) reduction in intrabacterial penetration

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Penicillin Inactivation by β-Lactamase Production by H. influenzae

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If H.influenzae does not produce beta-lactamase then penicillin can cause the bacteria to lyse. If beta-lactamse is produced, it will destroy penicillin. In order for penicillin to work, it must be taken with a beta-lactamase inhibitor, which will stop the destruction of penicillin so that it can bind to PBP.

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S. pneumoniae Resistance to β-Lactams by Target Alteration

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If the PBP site has a high affinity for beta-lactam antibiotic, it will cause PBP to be inactive; therefore inhibiting peptidoglycan synthesis. If the PBP target site is altered, it will have a low affinity for beta-lactam antibiotic; therefore PBP is active and the bacteria can undergo normal peptidoglycan synthesis.

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Bacteria can Aquire Resistance in Three Ways

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1) mutation DNA
2) transformation- microbial sex where DNA from one bacterium is taken up by another bacterium
3) worst! bacterium acquires a plasmid

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Decrease use in erthromycin

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reduction in group A of Streptococcus (study done in Finland)

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Unnecessary antibiotic use for viral illness is common, especially in respiratory tract infections, and has led to increasing rates of antibiotic resistance among...

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S. pneumoniae and other community-acquired pathogens

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Antibiotic Therapy

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Only when necessary! Treatment must not last too long and the dosage should not be too low

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Factors that contribute to antibiotic overuse

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lack of education, patients’ expectations, past experience, and economic incentives

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Acute nasopharyngitis (aka common cold)

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Antibiotic therapy is not justified in noncomplicated acute nasopharyngitis, even in children
Patients at risk must contact their doctor in the presence of signs indicating bacterial complications
Only proven complications, because they are possibly bacterial, require curative antibiotic therapy
Cold symptoms should be treated conservatively for 7 to 10 days before considering antibiotic therapy

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Otitis media (2 years and up)
"ear infection"

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Treat conservatively for 3 days prior to considering antibiotic therapy

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Acute Pharyngitis

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Only patients with acute pharyngitis caused by group A streptococcus (GAS) require antibiotic therapy
To determine the streptococcal origin, it is recommended that rapid diagnostic tests be used
In case of positive test, antibiotic therapy is necessary. In case of negative test, pharyngeal samples must be cultured and antibiotic therapy is not necessary in patients without risk of rheumatic fever.

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Acute Bronchitis In Healthy Adults

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No antibiotic therapy is the rule
Antibiotics may be considered secondarily in case of the association of chronic tobacco consumption, persistence of cough and purulent sputum beyond the seventh day of infection, and presence of diffuse bronchial rales by auscultation
Macrolides or cyclines should be preferred for 5 to 8 days’ treatment

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Community Acquired Pneumonia in Adult Outpatients

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Treatment of community-acquired pneumonia is generally antibiotic therapy
First-line antibiotic therapy should be rapidly initiated and given for 7 to 14 days
amoxicillin PO in case of pneumococcal suspicion, or macrolides in case of suspicion of “atypical” bacteria
Clinical reassessment is recommended after 3 days’ treatment

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Fluoroquinolones

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No longer recommended for gonorrhea infections. quinolones inappropriate for use on homosexual males or from infections acquired from Asia, Hawaii, or CA.

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Rocephin (ceftriaxone) or Suprax (cefixime)

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prescibe for uncomplicated gonorrhea
For patients with severe allergies to penicillin or cephalosporins, give one dose of 2 g azithromycin. But keep in mind that too much azithromycin will cause nausea and overuse can also lead to resistance.