Question 13

College Answer

13.1.   Apart  from  vancomycin,  list  three  antibiotics  that  have  activity  against  hospital acquired methicillin resistant staphylococcus aureus (MRSA).

•     Linezolid
•     Talavancin
•    Streptogramins (not currently available in Australia)
•     tigecycline

13.2     List an example of each of the three main classes of systemic antifungal agents.

•     Polyenes e.g. Amphotericin B
•     Azoles e.g. Fluconazole
•     Echinocandins e.g. caspofungin, andulafungin, micafungin

13.3.   Briefly outline the dosing adjustment and the monitoring necessary in patients with septic shock for each of the following  drug groups  in patients  with moderate  to severe renal dysfunction (without dialysis)

a) Aminoglycosides

b) Fluoroquinolones

c)  Beta Lactams

d)  Carbapenems

e)  Glycopeptides

Aminoglycosides	High initial dose and monitor trough concentrations. Extend interval. May be necessary  to decrease dose and monitor with MIC data
Fluoroqinolones	Reduce     frequency     but      maintain dose.  Monitor QT interval
Beta Lactams	Can reduce dose OR frequency Monitoring unnecessary
Carbapenems	As for Beta Lactams
Glycopeptides	High   dosing   on   day   one   dose adjustments according to Cmin and dependent on degree of renal dysfunction

Discussion

A good article on the antibiotic management options for MRSA lists the following substances:

• Tigecycline
• Linezolid (particularly for MRSA pneumonia, where vancomycin penetrates poorly)
• Quinupristin/dalfopristin
• Daptomycin
• Fosfomycin (usually to enhance the effects of other drugs)
• Rifampicin/fusidic acid (particularly for deep bone and joint infections)
• Telavancin, dalbavancin and oritavancin
• Ceftobiprole and ceftaroline
• Iclaprim
• Trimethoprim/sulfamethoxazole
• Moxifloxacin

So, really, we are spoilt for choice. MRSA in general is discussed in greater detail in the Required Reading section

As for the antifungal drugs, in brief summary:

• Polyenes like amphotericin and nystatin weaken fungal cell walls by binding to ergosterol.
• Azoles like fluconazole and voriconazole prevent the synthesis of ergosterol from lanosterol by inhibiting lanosterol 14 α-demethylase.
• Echinocandins like caspofungin inhibit fungal cell wall synthesis by blocking the synthesis of glucan by 1,3-β glucan synthase.

Antifungal pharmacology is explored in luxurious detail by Russell E. Lewis in his 2011 article for the Mayo Clinic Proceedings. Some of this detail has been condensed into a summary of antifungal pharmacology, available in the Required Reading section,

Question 13.3 very closely resembles Question 15.2 from the second paper of 2013, and will receive no further attention here.

Holt, S., and K. Moore. "Pathogenesis and treatment of renal dysfunction in rhabdomyolysis." Intensive care medicine 27.5 (2001): 803-811.

 

Welte, Tobias, and Mathias W. Pletz. "Antimicrobial treatment of nosocomial meticillin-resistantStaphylococcus aureus (MRSA) pneumonia: current and future options." International journal of antimicrobial agents 36.5 (2010): 391-400.

 

Lewis, Russell E. "Current concepts in antifungal pharmacology." Mayo Clinic Proceedings. Vol. 86. No. 8. Elsevier, 2011.