Antimicrobial Therapy Flashcards
Factors to consider with regard to principles of prescribing
Indication for antimicrobials Clinical diagnosis and severity assessment Patient characteristics Antimicrobial selection Regimen selection Liaison with laboratory
Common side effects/toxicities of antimicrobials
Allergic reactions GI Candida Liver Renal Neurological Haematological
Mechanisms of antibiotic resistance
Alteration of target site to reduce/eliminate the binding of a drug
Destruction or inactivation of antibiotic
Blockage of transport of antibiotic into the cell
Metabolic bypass
Pathogens with increasing resistance in hospitals
MRSA (methicillin resistant staph aureus)
MRSE (methicillin resistant staph epidermidis)
VRE (vancomycin resistant enterococcus)
VISA/GISA (vancomycin intermediate staph aureus)
ESBL (extended spectrum beta-lactamase gram -ve)
Multiresistant TB
Pathogens with increasing resistance in the community
HIV Food borne e.g. salmonella, shigella, H. pylori Malaria Pneumococcus Hep B and C E. coli O157 Lyme disease Legionnaire's
Antimicrobial therapy options
Empiric - without microbiology results
Directed - based on microbiology results
Antimicrobial prophylaxis options
Primary e.g. antimalarial, post-op, PEP
Secondary e.g. to prevent second episode
Methods of diagnosis
Clinical
Laboratory
Severity assessment
Patient characteristics affecting prescription
Age Renal function Liver function Immunocompromised Pregnancy Known allergies
Factors to consider when selecting antimicrobial
Guideline or individualised therapy Likely organism Empirical therapy or result-based therapy Bactericidal vs bacteriostatic drug Single or combination therapy Potential adverse effects
What should antibiotic selection be based on?
The known, or likely, causative organism
Likelihood of antibiotic resistance should also be considered
Features of bactericidal antimicrobials
Kill the bacteria
Act on cell wall
Indications include neutropenia, meningitis and endocarditis
Features of bacteriostatic antimicrobials
Inhibit bacterial replication by inhibiting protein synthesis and prevent colon growth
Require the host immune system to “mop up” residual infection
Useful in toxin-mediated illness
Give an example of a class of bactericidal and bacteriostatic antimicrobial
Bactericidal - beta-lactams
Bacteriostatic - macrolides
Advantages of single therapy
Simpler
Fewer side effects
Fewer drug interactions
Circumstances in which combination therapy is indicated
HIV and TB therapy
Slow organism turnover
Severe sepsis
Mixed infecting organisms
Factors to consider in regimen selection of antimicrobial therapy
Route of administration Dose Adverse effects Duration IV to oral SWITCH therapy Inpatient or outpatient therapy Therapeutic drug monitoring
Contraindications for oral therapy
Difficulty swallowing Malnourishment Vomiting Abnormal GI function Shock Organ dysfunction
What is the oral bio-availability
Ratio of drug level when given orally compared with the level when given IV
When is the IV route advisable
Severe or deep-seated infection
Where oral route is not reliable
When is liaison with laboratory necessary
Sending appropriate and relevant specimens
Receiving results
Monitoring
What is antimicrobial stewardship?
Making the best use of current antimicrobials
Antimicrobial management team
Antibiotic pharmacists Infectious disease doctors Acute medicine Medical microbiology Infection prevention and control GP
Classes of antimicrobials commonly used
Penicillins Cephalosporins Aminoglycosides Glycopeptides Macrolides Quinolones Other antibiotics Antifungals Antivirals Immunoglobulin
Mechanisms of action of antimicrobials
Inhibition of cell wall synthesis
Inhibition of protein synthesis
Inhibition of nucleic acid synthesis
Antimicrobial classes which inhibit cell wall synthesis
Beta lactams
Glycopeptides
Antimicrobial classes which inhibit protein synthesis
Aminoglycosides
Macrolides
Tetracyclines
Oxazolidinones
Antimicrobial classes which inhibit nucleic acid synthesis
Trimethoprim
Sulphonamides
Quinolones
Activity and main uses of bezylpenicillin/penicillin V
Streptococci
Neisseria
Spirochetes
Soft tissue, pneumococcal, meningococcal, gonorrhoea and syphilis infections
Activity and main uses of amoxicillin
Broad spectrum
UTI
RTI
Activity and main uses of flucloxacillin
Staphylococci
Staph aureus infection
Activity and main uses of co-amoxiclav
Broad spectrum (including anaerobes)
UTI
RTI
Soft tissue and surgical wound infections
Activity and main uses of piperacillin/tazobactam
Broad spectrum (including pseudomonas and anaerobes)
Neutropenic sepsis
Activity and main uses of Cefradine
Broad spectrum
UTI and soft tissue infection (first line)
Activity and main uses of Cefuroxime
Broad spectrum
UTI, RTI, surgical prophylaxis
Activity and main uses of Ceftriaxon/cefotaxime
Broad spectrum, especially effective against gram negative bacilli
Hospital infections e.g. bacteraemia, pneumonia, abdominal sepsis
Activity and main uses of Ceftazidime
Broad spectrum, particularly against gram negative bacilli and also active against pseudomonas
Pseudomonal infections in hospital patients and in cystic fibrosis patients
Activity and main uses of gentamicin/amikacin
Gram negative bacilli
Serious gram negative infections e.g. bacteraemia, endocarditis, neutropenic sepsis
Activity and main uses of clarithromycin/erythromycin
Streptococci, staphylococci, mycoplasma, chlamydia, legionella
Respiratory and soft tissue infection (if penicillin allergic)
STD
Activity and main uses of azithromycin
Relatively better for gram negatives such as haemophilus, chlamydia
Chlamydia
Activity and main uses of ciprofloxacin
Gram negative bacilli including pseudomonas, some activity against staphylococci and streptococci
Complicated UTI
Complicated hospital acquired pneumonia
Some GI infections
Activity and main uses of levofloxacin/moxifloxacin
Enhanced activity against staph/strep, less against pseudomonas
Active against pneumococcus, mycoplasma, chlamydia and legionella
2nd or 3rd line for pneumonia
Activity and main uses of vancomycin/teicoplanin
Gram positive bacteria only
MRSA
Patients allergic to penicillin
C. difficile
Activity and main uses of trimethoprim
Gram negative bacilli, some activity against staph/strep
UTI
Respiratory infection
MRSA
Activity and main uses of co-trimoxazole
Broad spectrum, pneumocystis jiroveci
Soft tissue infection, gangrene
Activity and main uses of clindamycin
Strep, staph, anaerobes
Soft tissue infection, gangrene
Activity and main uses of tetracycline/doxycycline
Strep, staph, chlamydia, rickettsiae, brucella
Q fever Brucellosis Chlamydia Atypical pneumonia MRSA
Activity and main uses of Rifampicin
Mycobacteria, meningococcus, staph
TB
MRSA
meningococcal prophylaxis
complicated staph infections
Activity and main uses of meropenem
Broad spectrum (broadest) including anaerobes and pseudomonas
2nd or 3rd line for hospital infections
Activity and main uses of metronidazole
Anaerobes, protozoa
Surgical infections, giargiasis, amoebiasis, trichomonal infections
Activity and main uses of linezolid
Gram positive bacteria only
2nd line agent for MSSA, MRSA, VRE
Activity and main uses of daptomycin
Gram positive bacteria only
2nd line agent for MSSA, MRSA, VRE
Activity and main uses of tigecycline
Very broad spectrum including MRSA, ESBL and anaerobes
3rd line for intra-abdominal sepsis
Soft tissue infections
Allergic reaction types
Immediate hypersensitivity e.g. anaphylactic shock
Delayed hypersensitivity e.g. rash, drug fever, SJS
Common GI adverse effects
Nausea
Vomiting
Diarrhoea
C. diff infection
Causes of candida infections
Broad spectrum penicillins, cephalosporins
Causes of liver adverse effects
All drugs, particularly tetracyclines and TB drugs
More likely if pre-existing liver disease
Causes of renal adverse effects
Gentamicin and vancomycin
More likely if pre-existing renal disease or on nephrotoxic medications
Neurological adverse effects and their causes
Ototoxicity - gentamicin, vancomycin
Optic neuropathy - ethambutol
Convulsions, encephalopathy - penicillins and cephalosporins
Peripheral neuropathy - isoniazid, metronidazole
Haematological adverse effects and their causes
Marrow toxicity
Megaloblastic anaemia - co-trimoxazole
What kind of pathogens are viruses?
Obligate intracellular
How do viruses replicate?
Utilise host cell enzymes in order to replicated
What stages of virus life cycle do most antivirals target?
Intracellular stages
What type of drug are most antivirals?
Nucleoside analogues (inhibit nucleic acid synthesis)
When might antiviral treatment be given?
Prophylaxis e.g. acyclovir for herpes
Pre-emptive therapy e.g. interferon/ribavarin for HCV
Overt disease e.g. acyclovir, oseltamivir
Suppressive therapy e.g. antiretrovirals
In what diseases is suppressive treatment needed?
Herpes viruses HSV1 and 2, VZV, CMV HIV Hepatitis B Hepatitis C Respiratory e.g. influenza
In what circumstances are antivirals used for herpes simplex?
Mucocutaneous involvement e.g. oral, genital, eyes
Encephalitis
Immunocompromised patients
In what circumstances are antivirals used for chickenpox?
In those at increased risk of complications or in the immunocompetent adult (within 24 hours of rash onset)
In what circumstances are antivirals used for shingles?
Within 72 hours of onset of symptoms
Antivirals used for HSV and VZV
Aciclocir
Valaciclovir
Famciclocir
Foscarnet
Aciclovir mode of action
Converted by viral thymidine kinase to ACVMP
ACVMP converted by host cell kinases to ACV-TP
ACV-TP completely inhibits and inactivated HSV-specific DNA polymerase
When have antivirals to be used in CMV?
Only to treat life-threatening or sight-threataening CMV infections
In neonates with symptomatic congenital CMV infection
Antivirals used for CMV
Ganciclovir
Valganciclovir
Cidofovir
Foscarnet
Antivirals used for chronic hepatitis B
Pegylated interferon alpha Nucleoside/nucleotide analogues Tenofovir Adefovir Entecavir Lamivudine Emtricitabine Telbivudine
Antivirals for chronic hepatitis C
Pegylated interferon alpha and ribavarin (may also add protease inhibitor e.g. telaprevir or boceprevir)
Daclatasvir, sofosbuvir, simeprevir
Antivirals used for influenza A or B
Oseltamivir
Zanamivir
Antiviral used in HSV and CMV resistant to aciclovir
Foscarnet
When is HIV resistance testing performed?
At a baseline diagnosis, failing therapy, or as a new treatment approach required for other reasons
When do trough and peak levels for aciclovir need to be monitored?
In patients with renal impairment
Classes of antifungals
Azoles
Polyenes
Echinocandins
Terbinafine
Uses of Azoles
Fluconazole - candida
Itraconazole - candida and aspergillus
Voriconazole - candida and aspergillus
Uses of polyenes
Amphotericin - candida and aspergillus
Nystatin - candida
Uses of echinocandins
Caspofungin, anidulafungin, micafungin - candida and aspergillus
Uses or terbinafine
Tinea, nail infection
