Infectious Diseases Flashcards
Antimicrobial selection
- Clinical diagnosis
- Obtain cultures/specimens
- Microbial diagnosis based on most likely organism or culture/test result
- Select appropriate medication
- May need to change drug based on culture/sensitivity test results
Empiric therapy:
treatment of an infection before specific culture information has been reported or obtained
Definitive therapy:
antibiotic therapy tailored to treat organism identified with cultures
Prophylactic therapy:
treatment with antibiotics to prevent an infection
Inhibit Cell Wall Synthesis
Beta-lactams [Penicillins (+/- Beta-lactamase inhibitors); Cephalosporins (3 generations); Monobactams; Carbapenems]
Glycopeptides
Fosfomycin
Inhibit Protein Synthesis
Aminoglycosides Ansamycins
Tetracyclines Glycylcyclines
Macrolides & Ketolides Oxazolidinones
Lincosamides Phenicols
Streptogramins
Inhibit Membrane Functions
Leptopeptides
Polymyxin
Anti-metabolites
Sulfonamides
Inhibit Nucleic Acid Synthesis
Fluoroquinolones
Furanes
Beta-lactams
Penicillins Cephalosporins (3 generations) Monobactams Carbapenems Glycopeptides Fosfomycin All antibiotics in this category contain a beta lactam ring that is essential for activity, but is also susceptible to hydrolysis by beta-lactamases, destroying the antimicrobial action of the compound. Beta-lactamase-producing staphylococci cause about 80% of community-acquired staph infections.
Penicillins
Inhibit the biosynthesis of peptidoglycan bacterial cell wall
Well-absorbed from GI tract, but several are unstable in acid
Bound to proteins, therefore have good distribution to most tissues
Small amount is metabolized, most excreted as unchanged drug in the urine.
Natural penicillins:
Streptococcus, some Enterococcus strains, some non-penicillinase-producing Staphlococcus
Aminopenicillins
Greater activity against gram-negative bacteria due to enhanced ability to penetrate the outer membrane organisms
Used for gram-negative urinary and gastrointestinal (GI) pathogens E. coli, Proteus mirabilis, Salmonella, some Shigella species, and Enterococcus faecalis; active against the common gram-negative respiratory pathogens Moraxella catarrhalis (and Haemophilus influenzae type B)
Aminopenicillins have a broader spectrum
Combination with beta-lactamase inhibitors to broaden their spectrum:
Clavulanate, sulbactam, tazobactam
Amoxicillin/clavulanate (Augmentin) combination is an antibiotic that belongs to the group of medicines known as penicillins and beta-lactamase inhibitors. It works by killing the bacteria and preventing their growth.
Probenecid
Gout medication =
Prolongs the half-life of PCNs and cephalosporins and increases risk for toxicity.
If a patient has a failed amoxicillin course
If a patient has a failed amoxicillin course and the infection does not resolve or recurs within a few weeks, you would then order Amoxicillin-clavulanate (to add the beta-lactamse inhibitor).
Amoxicillin is the antibiotic of choice unless the child received it within the previous 30 days, has concurrent purulent conjunctivitis, or is allergic to penicillin; in these cases, clinicians should prescribe an antibiotic with additional β-lactamase coverage.
Amoxicillin is first-line therapy
For acute otitis media (AOM), pharyngitis, and sinusitis.
Penicillin (PCN) is first-line therapy
For streptococcal pharyngitis & syphilis.
Amoxicillin/clavulanate (Augmentin) is first-line therapy
For infection following bites, including human.
Additional uses of PCNs
Sinusitis is treated with a penicillin if the mucopurulent drainage and cough have not improved after 10 days. Pneumonia, STIs, UTI, and Wound Infections
Endocarditis prophylaxis
Helicobacter pylori
Lyme Disease
Clinical Uses of Beta-Lactamase Inhibitor
Human and animal bites Aspiration pneumonia Foot infections in diabetic patients Sinusitis Resistant otitis media Lung abscess Does not cover MRSA
Piperacillin and tazobactam(Zosyn):
About as broad as you can get
Adverse drug reactions (ADRs) of PCNs
May cause serious immediate allergic reactions. Reactions occur within 2 to 30 minutes of administration.
Patients may be given desensitization therapy.
Rash: maculopapular rash occurs 9% of time that is not allergic in origin, appears 7 to 10 days into treatment.
GI: diarrhea, nausea/vomiting (n/v), addition of clavulanate increases risk of diarrhea
Fungal overgrowth
C. difficile colitis
Most are pregnancy category B.
Anaphylactic shock Type I
Most serious, urticaria, pruritus.
Anaphylactic shock Type II
Hemolytic anemia, neutropenia (nafcillin), thrombocytopenia.
Anaphylactic shock Type III
Serum sickness (rare-urticaria, fever joint swelling, angioneuroticedema, pruritus, bronchospasm-7-12 days after), interstitial nephritis(methicillin).
Anaphylactic shock Type IV
Contact dermatitis.
Sinusitis Common Pathogens
Strict criteria: persistent, not improving for at least 10 days. Common pathogens S. pneumoniae: 30% H. flu: 20% Moraxella catarrhalis: 20% Rarely, Staphylococcus
Antibiotic Choices for Sinusitis
Amoxicillin first line:
80 to 90 mg/kg/day in high-risk children;
45 mg/kg/day in low-risk children
Adults: 500 mg three times/day, or high-dose Augmentin
Antibiotic Choices for Sinusitis for penicillin-allergic patients
Children: cefdinir, cefuroxime, or cefpodoxime
Adults: doxycycline or respiratory fluoroquinolone (levofloxacin)
Sinusitis: If started on Augmentin & worsening symptoms:
Children: consider cefdinir, cefuroxime, cefpodoxime
Adults: consider respiratory fluoroquinolone (levofloxacin).
Cephalosporin pharmacodynamics
Structurally and chemically similar to PCNs
Inhibit mucopeptide synthesis in the bacterial cell wall. Bactericidal
All cephalosporins penetrate poorly into ICF and the vitreous humor.
Cephalosporins First Generation
Cefazolin (Ancef), Cephalexin (Keflex), Cefadroxil
Used for gram positive skin and soft tissue infections
Primarily active against gram-positive bacteria, S. aureus and S. epidermidis
Cephalosporins Second Generation
Cefuroxime (Ceftin), Cefaclor
Active against same as first generation, plus Klebsiella, Proteus, E. coli
Cephalosporins Third Generation
Ceftriaxone, Cefotaxime, Ceftazidime
Used for broader indications
More active against gram-negative bacteria; Does not cover MRSA; Treats community acquired bacterial meningitis
Cephalosporins Fourth Generation
Cefepime (Maxipime)
Resistant to beta-lactamase
Primarily active against gram-positive bacteria
Four generations of cephalosporins
Progression from 1st to 4th reflects an increase in gram – coverage and loss of gram + cover.
Cephalosporin pharmacokinetics
Oral formulations absorbed from GI tract
Widely distributed to most tissues
Some highly bound to proteins
Some are metabolized to less active compounds, most excreted via kidneys, as unchanged drug
ADRs of cephalosporins
Allergies, skin rashes, arthralgia, coagulation abnormalities, anemia, neutropenia, leukopenia, thrombocytosis, fever, seizures, renal/hepatic failure
Monitor: For diarrhea (C. difficile) Renal function, if prolonged therapy
Cephalexin (Keflix)
Strep pharyngitis
Skin infections
Second-line drug for UTI
Ceftriaxone
GC/chlamydia
Cephalosporin Third Generation
Cefexime
GC/chlamydia
Second-line drug for UTI
Cefpodoxime
Community-acquired pneumonia
Second-line drug for UTI
Cefuroxime
Community-acquired pneumonia
Parenteral Ceftriaxone followed by oral Cefpodoxime
Community-acquired pneumonia
Most cephalosporins are pregnancy category
B
Cefazolin (Ancef)
Strep pharyngitis
Skin infections
Cefadroxil
Strep pharyngitis
Skin infections
Ertapenem (Invanz)
Carbapenem
Parenteral β lactamantibiotics, β lactamaseresistant. Broadest spectrum of activity.
Doripenem (Doribax)
Carbapenem
Imipenem (Primaxin)
Carbapenem
Parenteral β lactamantibiotics, β lactamaseresistant. Broadest spectrum of activity.
Meropenem (Merrem)
Carbapenem
Parenteral β lactamantibiotics, β lactamaseresistant. Broadest spectrum of activity.
Carbapenems
Bactericidal. Inhibits cell wall synthesis.
Very resistant to hydrolysis by most beta lactamases.
Most broad-spectrum agent available.
Gram + and Gram – coverage.
Great for polymicrobial infections.
Adverse Effects of Carbapenems
Neurotoxicity, Seizure activity
Risk factors for seizures: impaired renal function, improper dosing, CNS disorder
If the patient has a h/o seizure disorder and this class is needed: choose Merrem over others.
GI side effects: N/V/D
Drug interactions: Don’t use with Probenicid
Carbapenems treat
Streptococci (Including penicillin resistant S. Pneumoniae) Enterococci Enterobacteriaceae Pseudomonas Acinetobacter Anaerobes, including B. fragilis
NOT effective against Enterococcusfaecium, MRSA and Clostridium difficile
Skin, bone, joint, intra-abdominal, and lower resp infections
Fluoroquinolones
Interfere with enzymes required for the synthesis of bacterial DNA.
Extensive gram-negative activity.
Take on empty stomach for best absorption.
ADRs of Fluoroquinolones
Black Box Warning: Tendonitis/tendon rupture. Can have delayed onset, 120 days to months after administration.
Elderly and children <18 y/o at higher risk.
GI: Pseudomembranous colitis
CNS: Sleep disorders, dizziness, acidosis. Do NOT prescribe for MG.
Renal/hepatic failure
CV: Angina, atrial flutter, prolonged QT
Pregnancy Category C.
Clinical use and dosing of Fluoroquinolones
Complicated UTI Pyelonephritis infections Chronic bacterial prostatitis Pneumonia/chronic bronchitis exacerbation PCN-resistant S. pneumoniae Skin infections Bone/joint infections Complicated intraabdominal Infectious diarrhea
Clindamycin (Cleocin)
Lincosamide
Inhibits protein synthesis.
No gram-negative activity.
Gram-positive activity: corynebacterium acnes, gardnarella vaginalis, some MRSA
Oral dosing completely absorbed, not affected by gastric acid.
Clindamycin (Cleocin) ADRs
Black Box Warning for severe colitis
Stop & to call provider diarrhea if severe.
Rash, burning, itching, erythema
Transient eosinophelia, neutropenia, thrombocytopenia
Azithromycin
Macrolide
Unique; does not extensively inhibit CYP3A4
Very common causes of drug induced liver injury.
Chlamydia
Pertussis
Clarithromycin
Macrolide Eliminated mostly by kidneys H. Pylori infections Cat C Pertussis
Erythromycin
Macrolide
Pertussis
Telithromicin
Macrolide
Fidaxomycin
Macrolide
Macrolide
DOC for community-acquired PNA
Inhibits RNA-dependent protein synthesis.
Iinhibited by acids (require enteric coating)
Atypical and intracellular organisms resistant to beta-lactam antibiotics are often susceptible.
Potent inhibitors of CYP 450 3A4.
Metabolized by liver; excreted in bile & urine.
ADRs of Macrolides
Dose-related GI: N/V, abdominal pain, cramping, diarrhea
Skin: urticaria, bullous eruptions, eczema, Stevens-Johnson syndrome
Cardiac: prolonged QT
Monitor for hearing loss
Fidaxomicin
Not a typical macrolide
Specifically used for C Difficile
Oxazolidinones
Inhibit bacterial ribosomal protein synthesis.
Most effective against gram-positive bacteria.
Well-absorbed orally. Does not use CYP 450 enzymes.
Avoid tyramine-rich foods.
Linezolid
Oxazolidinone
Tedizolid
Oxazolidinone
Oxazolidinones ADRs
Diarrhea, HA, nausea
Myelosuppression reported-resolves w/ drug discontinuation. Check CBC if treatment > 2 weeks.
Oxazolidinones Indications
Pneumonia
Complicated skin infections
Use less expensive drug first
Pregnancy Category C
Sulfonamides
Block folic acid synthesis
Anorexia, N/V, diarrhea, abdominal pain
Jaundice/hepatitis
Avoid in G6PD deficiency. Can result in life-threatening bone marrow suppression.
Anti-metabolite, folate antagonist
Gram + and gram –
Does not cover pseudomonas, anaerobes, or group A strep
Silver Sulfadiazine (Silvadene): topical agent frequently used in treating burns
Trimethoprim
Inhibits DNA synthesis
Anorexia, N/V, diarrhea, abdominal pain
Nitrofurantoin
Inhibits acetyl coenzymes.
Inhibit gram-positive and gram-negative bacteria:
E. coli, S. pyogenes, S. pneumoniae, H. influenza, and some protozoa
Anorexia, N/V, diarrhea, abdominal pain
Jaundice/hepatitis
Long-term use check CBC
Pregnancy Cat B
Fosfomycin
Inactivates enolpyruvyl transferase
Anorexia, N/V, diarrhea, abdominal pain
Pregnancy Cat B
Trimethoprim-sulfamethoxazole (Bactrim)
UTIs, MRSA, bronchitis, pneumocystis pneumonia
Acute exacerbations of chronic bronchitis due to susceptible strains of Streptococcus pneumoniae or Haemophilus influenza: Bacterial meningitis, Pneumocystis (Carinii) Jiroveci Pneumonia; Sepsis; Shigellosis, Skin and soft tissue infection
Long-term use check CBC
Stomatitis, rashes, increased hypersensitivity reactions, Stevens-Johnson Syndrome, photosensitivity
Headache, dizziness, peripheral neuropathy
Pregnancy Cat C
Tetracyclines
Bind reversibly to the small subunit of the bacterial ribosome
Useful for gram positive, gram negative & intracellular organisms
Food decreases absorption. Milk and calcium decrease absorption.
Tetracyclines are Pregnancy Category X [except doxycycline (Pregnancy Cat D)].
Do not prescribe to pregnant women, lactating women, or children less than age 8 years (due to bone/teeth effects).
Most impacted by antacids & supplements
Minocycline
Popular acne med in the tetracycline family.
Associated with pseudotremor cerebri (idiopathic intracranial hypertension).
Pt would c/o headache, blurred vision while taking minocycline. So, if pt c/o headaches while taking the med, should evaluate for this condition to protect against vision loss. Rare but notable ADR.
Doxycycline
First-line therapy for Chlamydia.
Known to cause photosensitivity.
If treating chlamydia in woman of child-bearing age taking oral contraceptives, instruct to use a back-up method of birth control until her next menses.
Never use past expiration date as may cause toxicity.
Vancomycin
Lipoglycopeptide. Inhibits cell wall synthesis.
Used for severe gram-positive infections, such as MRSA
Drug trough level is most commonly monitored especially if > 4 days of med needed, or receiving other nephrotoxic meds.
Trough drawn 30 minutes prior to next dose. Draw peak level of vancomycin at least 1 hour past dose administered.
ADRs of Vancomycin
Ototoxicity (transient or permanent)
Nephrotocity
“Red Man” syndrome if infused too fast
Aminoglycosides
Inhibits Protein Synthesis
Excellent coverage against gram - (including pseudomonas).
Have synergy with PCN against Staph and enterococcus
Adverse events: Nephrotoxicity and ototoxicity
Less toxic with once daily dosing
Monitor drug levels
Monitor kidney function
Auditory toxicity symptoms: hearing loss, tinnitus, nausea, vomiting, vertigo
Gentamycin
Aminoglycoside
Tobramycin
Aminoglycoside
Amikacin
Aminoglycoside
Aminoglycoside ADRs
Nephrotoxicity and ototoxicity Less toxic with once daily dosing Monitor drug levels Monitor kidney function Hearing loss, tinnitus N/V, vertigo
Metronidazole (Flagyl)
Inhibits DNA and protein synthesis.
60-80% excreted via kidneys.
Treats both parasitical and bacterial infections.
Treat protozoal infections T. vaginalis, G. lamblia, Entamoeba histolytica, H. pylori, Clostridium difficile.
Pregnancy Category B
ADRs: Anorexia, nausea, abdominal pain. Dizziness, headache, metallic taste.
Avoid alcohol.
Nitazoxanide (Alinia)
Interferes w/ PFOR enzyme-dependent electron transfer reaction
Excreted 66% in feces, 33% in urine.
Treat Giardia lamblia and Cryptosporidium. Treat protozoal infections T. vaginalis, G. lamblia, and E. histolytica.
Treats diarrhea caused by parasitic infection.
Pregnancy Category B
ADRs: Anorexia, nausea, abdominal pain.
Tinidazole (Tindamax)
Inhibits DNA and protein synthesis.
Mostly excreted by liver, and lesser amount via kidneys.
Active against amebiasis, giardiasis, and trichomoniasis.
Pregnancy Category C
ADRs: Anorexia, nausea, abdominal pain.
Avoid alcohol.
Isoniazid (INH)
Inhibit synthesis of mycolic acids.
Highly variable and dependent on acetylator status.
ADRs: Peripheral neuropathy, hepatotoxicity
Pyridoxine (Vitamin B6) given to treat neuropathy and also given prophylactically to prevent
Ethambutol
Inhibit synthesis of mycolic acids.
Inhibits synthesis of arabinogalactan, an essential component of mycobacteria cell walls.
ADRs: optic neuritis
Rifampin
Binds to the beta subunit of mycobacteria DNA-dependent RNA polymerase and inhibits RNA synthesis.
Potent inducer of liver metabolism, be aware when using w/ other meds.
ADRs: hepatotoxicity, ^LFTs, neutropenia, thrombocytopenia, orange secretion discoloration - tears, urine, sweat (harmless)
Inducer of CYP 450 enzyme.
Pyrazinamide
ADRs: hepatotoxicity
Streptomycin
Aminoglycoside, used to treat TB.
Watch for ototoxicity & nephrotoxicity.
Capreomycin
Aminoglycoside, used to treat TB.
Watch for ototoxicity & nephrotoxicity.
