Antimicrobial Pharmacology Flashcards
As part of the “start smart, then focus” antimicrobial stewardship programme, when should a clinical review and decision be made about focusing or changing antimicrobial therapy?
At 48 hours
Name two (antibiotic) core drugs that have a narrow therapeutic index
Gentamicin and Vancomycin
What pathogens are commonly implicated in the aetiology of CAP?
Streptococcus pneumonia
Haemophilus Influenza
Klebsiella pneumonia
S. Aureus
Atypical organisms
Viral (up to 13%)
What investigations should be carried out when considering a diagnosis of CAP?
- CXR
- Sputum sample
- Sputum/throat swab for viral culture and immunofluorescence if immunocompromised patient or creatures suggestive of influenza during flu season
- Serum and urine for pneumococcal and legionella testing if atypical features
What is the CURB-65 score used for?
To aid decisions regarding treatment of pneumonia
What clinical signs are implicated as indicators of pneumonia severity?
CURB-65 score: 1 point for each of the following-
- Confusion (new onset/ AMT < or = 8)
- Urea > 7 mmol/L
- RR > or = 30/min
- BP (SBP < 90 mmHg and/or DBP <60 mmHg)
> or = 65 years old
0-1: PO abx or home tx
2: Hospital tx
3 or >: Severe pneumonia, consider ITU (mortality 15-40%)
What factors should be considered when choosing an antibiotic for the tx of CAP?
- Allergies, CURB-65 score (but also clinical picture), previous abx, recent travel, hobbies, renal function, hepatic function.
Discuss with microbiology if recent flu
Is there any need to isolate patient? (e.g. flu / TB risk) Discuss with infection team
How do you calculate ideal body weight?
IBW male = 50 kg + (2.3 x every inch over 5 ft)
IBW female = 45.5 kg + (2.3 x every inch over 5 ft)
What risks are associated with Gentamicin (aminoglycoside)?
Nephrotoxic. Monitor drug levels and serum creatinine. Also ototoxicity, vestibular toxicity.
Contraindications of gentamicin
Severe renal or liver failure, ascites, burns, high cardiac output states (e.g. anaemia, Paget’s), children, pregnancy
Signs of Gentamicin toxicity
Tinnitus, deafness, nystagmus, vertigo, renal failure
What is the trough level of Gentamicin and when is this measured?
Trough level should be <1 mg/L, which should be measured just before the next dose
What are the Beta-lactam antibiotics?
Penicillins- Amoxicillin and Flucloxacillin
Drug class: Beta lactam antibiotic + Beta-lactamase inhibitor
Co-Amoxiclav
Drug class of vancomycin?
Glycopeptide
Drug class of Doxycycline?
Tetracycline
Drug class of Clarithromycin, Erythromycin?
Macrolide
Drug class of Gentamicin?
Aminoglycoside
Drug class of Ciprofloxacin?
Quinolones
Drug class of Metronidazole?
Nitroimidazole
60-80% of cases of uncomplicated Pyelonephritis are caused by what organism?
E.Coli (gram negative)
MOA: Inhibition of bacterial cell wall synthesis. Inhibit enzymes responsible for cross-linking peptidoglycans in bacterial cell walls
Cephalosporins
Interaction: _________________ enhance the coagulation effect of warfarin by killing normal gut flora that synthesise Vitamin K.
Can cause nephrotoxicity if given with Gentamicin, Ibuprofen and celecoxib
Cephalosporins
Adverse effects: GI upset is common (abdominal pain, diarrhoea). Less frequently, can cause C.diff. Leukopenia.
Cephalosporins
Ceftriaxone is a _____ generation broad spectrum antibiotic
Third (Remember TRI and third)
Which of the Cephalosporin drugs can be used to treat Pseudomonas infections?
Ceftazidime
Indications: acute pyelophritis, lower UTIs, HAP
Cephalosporins
DOC in MRSA infections?
Vancomycin
Indication: NARROW SPECTRUM DRUG. Mainly against Gram-positive bacteria, including MRSA.
Vancomycin
Adverse effects of this drug class include “infusion reaction” (formerly known as “red man syndrome”), nephrotoxicity and ototoxicity
Glycopeptide (Vancomycin)
MOA: Inhibits peptidoglycan formation. Prevents incorporation of NAM and NAG peptide units from being incorporated into the peptidoglycan matrix, which forms the major structural component of Gram+ cell walls
Vancomycin
MOA: Inhibition of protein synthesis in the 50s subunit of the bacterial ribosome
Clarithromycin (Macrolide)
(Also Chloramphenicol has same MOA)
Indication: Broad spectrum antibiotic to treat Strep pyogenes, Pneumococcal infections, and cell wall deficient bacteria (Chlamydia). Examples include cellulitis, CAP, HAP, and H.pylori (in combination with other drugs)
Clarithromycin (macrolide)
Adverse effects of this drug class include GI effects and PROLONGATION OF QT INTERVAL, which can lead to ARRYTHMIAS
Macrolides (Clarithromycin, Erythromycin)
Drug interaction: INHIBITOR of p-450 enzyme
Macrolides
(“Sickfaces” inhibit)
Sodium valproate, Isoniazid, Cimetidine, Ketoconazole, Fluconazole, Alcohol & grapefruit juice, Chloramphenicol, Erythromycin, Sulfonamides, Ciprofloxacin, Omeprazole, Metronidazole
Important adverse effects include “Gray baby syndrome” (vomiting, diarrhoea, flaccidity, low temp, and an ashen-gray colour when prescribed in neonates) and also severe bone marrow depression (PANCYTOPENIA)
Chloramphenicol
Interaction: Inhibits CYP3A4 and CYP2C19, preventing the metabolism of drugs
Chloramphenicol
Adverse effects include DEPOSITION IN TEETH, bone growth inhibition, phototoxicity, and gastric discomfort
Doxycycline
MOA: This drug binds reversibly to the 30s subunit of the bacterial ribosome. This action prevents binding of tRNA to the mRNA- ribosome complex, thereby inhibiting bacterial protein synthesis
Doxycycline
Interaction: Enhances anticoagulant effect of Warfarin due to competitive interaction for albumin binding
Doxycycline
Which two core antibiotics are given IV as they are not absorbed orally?
Vancomycin and Gentimicin
MOA: Inside the cell, they bind the 30s ribosomal subunit and cause 3 effects- block formation of the initiation complex, miscoding of amino acids in the emerging peptide chain d/t misreading of the mRNA, block translocation on mRNA
Gentamicin
Adverse effects of Gentamicin?
Nephrotoxic, ototoxic
MOA: Inhibition of DNA gyrases- topoisomerase II and IV- which are needed for supercoiling, replication, and separation of circular bacterial DNA —> rapid bacterial cell death
Ciprofloxacin (Quinolones)
Interactions: Inhibits CYP1A2-mediated metabolism and may inhibit CYP3A4 metabolism.
Should be avoided with dairy products
Ciprofloxacin (Quinolones)
Adverse effects: TENDONITIS, TENDON RUPTURE, PROLONG QT INTERVAL, nausea, vomiting, headache, dizziness, CNS effects (hallucinations, anxiety, insomnia, confusion, seizures) peripheral neuropathy, phototoxicity
Ciprofloxacin (Quinolones)
Are the following bacteria gram negative or gram positive?
E. Coli
Klebsiella
Proteus
Pseudomonas
Enterobacter
Gram negative
What is the first choice of antibiotic for uncomplicated pyelonephritis?
Cefalexin (Cephalosporin)
Other choices include Co-Amoxiclav and Ciprofloxacin, depending on result of MC&S
First choice of IV antibiotic in Pyelonephritis if patient is vomiting or extremely unwell?
Co-amoxiclav or Ceftriaxone
Choice of antibiotic for pyelonephritis in patient who is pregnant?
Cefalexin (not known to be harmful in pregnancy or breastfeeding)
Most common organisms causing cellulitis? (2)
Streptococcus pyogenes and Staph aureus
First line choice of drug in cellulitis (oral)?
Flucloxacillin (Penacillin)
Which two drug classes bind to the 50s subunit of bacterial ribosomes, blocking transpeptidation?
Macrolides and Chloramphenicol
Which of the following sx may be a signal to the physician to stop gentamicin therapy?
Eosinophilia, headache, nausea, salivation, tinnitus
Tinnitus
MOA of tetracycline antibiotics?
Binds reversibly to the 30s subunit of the bacterial ribosome.
Which drug class is contraindicated in children < 8 due to deposition in bone and teeth, as well and stunting growth?
Tetracyclines (Doxycycline)
Which of the following antibiotics may have contributed to tendon rupture?
Amoxicillin/clavulinic acid
Cefalexin
Ciprofloxacin
Minocycline
Ciprofloxacin (Quinolones)
