C.16

Question 1

Clindamycin. Streptogramins. Oxazolidinones. Fusidans

Answer 1

1. Lincosamides: Clindamycin
2. Streptogramins: Quinupristin/Dalfopristin
3. Oxazolidinones: Linezolid

Question 2

Clindamycin

Answer 2

MOA: Bacteriostatic,
Binding to the 50S subunit, blockade of protein synthesis → inhibition of peptidyl tRNA translocation from acceptor to donor site;
Spectrum: Gram (+) cocci (incl. Staph. osteomyelitis, MRSA), mixed or anaerobe infections (B. fragilis, Clostridium, G.vaginalis→ clindamycin for anaerobes above the diaphragm, metronidazole for anaerobes below the diaphragm. Some protozoa (P. falciparum, Toxoplasma, Pneumocistis Jirovecii);
Resistance due to: Due to modification (methylation) of ribosomal binding site (MLSB resistance ), Enzymatic inactivation, Intrinsic resistance: poor penetration via outer membrane of Gram (-);
Pharmacokinetics: 80-90% absorption p.o, good distribution, NOT CNS, high concentration in abscesses + bones, Eliminated by the liver → bile/urine, Given 3x/day;
IND:
-Gram + cocci (→ Skin & soft tissue infections: Staph, Strep → ex. cellulitis. Community aquired MRSA. Osteomyelitis: Staph. Endocarditis: Prophylaxis),
-Anaerobes (→ Lung abscess: B. Fragilis → aspiration pneumonia. Gas gangrene: C.perfringens).
-Inflammatory acne: topical against skin anaerobes. Polymicrobial infections of female genital tract (→ Gentamicin-Clindamycin combination. Bacterial vaginosis: Gardnerella vaginalis);
ROA: P.O, Parentral;
SEs: Risk of severe dysbacteriosis (incl. Pseudomembranous colitis caused by C.diffiile)

Question 3

Quinupristin / dalfopristin

Answer 3

Streptogramin B:A
Ratio: 30:70% (Quinupristin/Dalfopristin);
MOA: Bactericid, Binds the 50S ribosomal subunit → inhibit protein synthesis elongation. blocking the exit channel on the ribosome through which nascent polypeptides are extruded;
Spectrum: Gram (+) cocci, incl. MDR strains (MRSA, VRSA), E. Faecium, but NOT E. Faecalis;
Additional sensitivity to: Mycoplasma, chlamydia, legionella, M. Catharrhalis, H. Influenzae;
Resistance due to: Modification of quinupristin binding site (MLSB resistance), Enzymatic inactivation of dalfopristin or efflux;
Pharmacokinetics: I.V administration (1h infusion via a central venous catheter) - 3x/day, T1/2 short: 1h (→ but high concentration in Leukocytes), Elimation mostly with faeces (→ not dependent on kidney function);
IND: Reserve antibiotic!!! → indicated only if other antibiotics are not effective → especially E. Faecium (NOT E.FAECALIS!!), other gram (+) cocci;
SEs: GI problems (nausea, vomiting, diarrhea), Myalgia, arthralgia, local irritation at the site of infusion, Increased bilirubin, allergy;
Interaction: Inhibition of CYP3A4 → increased level of benzos, cyclosporine, warfarin, antiretroviral drugs

Question 4

Linezolid

Answer 4

MOA: Bacteristatic, (only for streptococci Bactericidal!) Inhibits protein synthesis by preventing initiation of synthesis.
Unique binding site at the 50S subunit - no cross resistance with other drugs!;
Spectrum: Therapautically relevant part: Gram (+) bacteria! Strep-, staph-, enterococci (incl. MRSA, VRSA, VISA, VRE), Gram (+) anaerobic cocci, Gram (+) rods;
ROA: P.O: 2x day, good absorption, I.V also possible;
Pharmacokinetics: Good distribution ALSO CNS, In part metabolized - excreted with urine, bile;
IND: Nosocomial or community-acquired pneumonia, Severe skin and soft tissue infections with staph or strep, RESERVED for multidrug-resistant gram (+) bacteria;
SEs:
-Myelosuppression - usually mild, but weekly blood control is needed!,
-GI problems (Diarrhea, nausea, vomiting),
Headache, allergy, transaminase elevation, Reduced male fertility, Possible risk of cheese reaction (diet!!) → one of its metabolites is a MAO-inhibitor

Question 5

MLSB

Answer 5

resistance to macrolides, Lincosamides, streptogramin B

Question 6

Which pathogen is streptogramin INEFFECTIVE against?

Answer 6

E. faecium