Infectious Disease I: Background & Antibiotics

Teflaro

Brand name for ceftaroline

Clindamycin

Which antibiotic requires a D-test to be performed prior to use for MRSA skin soft tissue?

Tetracyclines, macrolides & quinolones

Which agents cover atypical pathogens?

Cubicin

Brand name for daptomycin

Doxycycline, ceftaroline & daptomycin

Which antibiotics are expected to have activity against MRSA?

Metallic taste in the mouth

Metronidazole side effect

During therapy and for 3 days after the last dose

How long should alcohol be avoided while taking metronidazole?

Flushing, abdominal cramping, nausea & vomiting

What can happen if you drink alcohol while taking metronidazole?

If patient is obese, use adjusted weight for dosing. The dose used most commonly for extended interval dosing is 7 mg/kg (but may range from 4-7 mg/kg)

Aminoglycoside dosing

≥2

What vancomycin MIC value would lead you to consider other antibiotics?

Sulfa allergy

What allergy should you look for when considering Bactrim?

Flagyl

Brand name for metronidazole

1:1

Metronidazole conversion ratio for IV:PO

Yes

Is nafcillin a vesicant?

Ampicillin/sulbactam & ertapenem

Antibiotics that are only compatible with NS

Second generation: better gram-negative activity compared to 1st generation, with similar grame-positive activity. Effective at treating Streptococci, MSSA and Gram-negative bacteria associated with mild-moderate foot infections

What generation of cephalosporin is cefuroxime?

Chlamydia, Mycoplasma pneumoniae, mycobacterium avium complex, travelers’ diarrhea, CAP & COPD exacerbations

Azithromycin common uses

Tetracyclines and quinolones

What antibiotics should be separated from divalent cations (multivitamins: calcium, iron, magnesium, zinc) as they may inhibit absorption through chelation?

Strong CYP3A4 inhibitor, can prolong the QT interval when combined with other medications known to prolong the QT interval, has a warning for hepatotoxicity & has a contraindication with simvastatin due to an increased risk of muscle toxicity (myopathy)

Clarithromycin drug interactions

Zithromax

Brand name for azithromycin

All macrolides

Which macrolides have a risk for QT prolongation and should be used cautiously in patients with cardiovascular disease or those taking other QT prolonging drugs?

Gram-positive pathogens (MRSA and VRE). It does not have activity against gram-negative pathogens or anaerobes

Linezolid coverage

Thrombocytopenia, anemia & leukopenia

Because linezolid is associated with bone marrow suppression, what should be monitored with longer treatment courses?

Aminoglycosides, fluoroquinolones, daptomycin

Which antibiotics are concentration-dependent?

Potent CYP2C9 inhibitor, has 1:1 conversion from IV:PO, excellent gram-positive, gram-negative and opportunistic pathogen coverage, should be dose reduced for CrCl <30 mL/min, a positive Coombs test in the labs (along with decreasing hemoglobin/hematocrit) would indicate the presence of hemolytic anemia and Bactrim should be discontinued

TMP/SMX important information

Associated with drug-induced lupus, may increase the risk of sunburn, should be separated when given with antacids, should not be used in children younger than 8 years old or in patients who are pregnant due to risk of tooth discoloration, bone growth retardation and reduced skeletal development, phosphate binders like fosrenol also decrease minocycline absorption

Minocycline important information

Zyvox, Flagyl, Avelox, Vibramycin

Which antibiotics have excellent bioavailability suitable for a 1:1 IV:PO conversion

Vancomycin and aminoglycosides

Which antibiotic agents are associated with ototoxicity?

Meropenem, metronidazole, ampicillin/sulbactam, cefoxitin

Which antimicrobial agents have activity against Bacteroides fragilis?

Strep. pyogenes (Group A strep)

What organism would show up as gram-positive cocci in chains?

All the carbapenems, except Invanz

Which carbepenems cover Pseudomonas aeruginosa?

Invanz

Brand name for ertapenem

Zyvox

Brand name for linezolid

Tygacil

Brand name for tigecycline

Aerobic (Stretococci, Staphylococci) and anaerobic gram-positive pathogens

Clindamycin’s spectrum of activity

Avelox

Brand name for moxifloxacin

Vancocin

Brand name for vancomycin

Augmentin

Brand name for amoxicillin/clavulanate

Inactivates beta lactamase enzymes, which extends the activity (or coverage) of the drug

Clavulanate or clavulanic acid MOA

TMP

Which component of Bactrim is used for dosing?

Bactrim DS: TMP 160 mg; Bactrim SS: TMP 80 mg

Bactrim DS vs. SS dosing

Oritavancin (Orbactiv) and dalbavancin (Dalvance)

What antibiotics have a similar spectrum of activity to vancomycin, but are a one-time dose?

Neurotoxicity, nephrotoxicity & ototoxicity

Toxicities associated with aminoglycosides

Severe and possibly fatal colitis

Clindamycin boxed warning

Risk of superinfections including risk of C. difficile-associated diarrhea

What warning do all antibiotics carry?

Macrolide antibiotic, not effective for treating viral infections, should be taken with food to minimize stomach upset, should be stored under refrigeration, major inhibitor of 3A4, azithromycin has fewer clinically significant drug interactions than erythromycin or clarithromycin

Erythromycin important information

Subjective: patient-reported symptoms based on the site of infection; Objective: observable findings, fever (≥100.4 F), laboratory parameters: leukocytosis (WBC >11,000 cells/mm3), elevated bands (left shift), elevtaed markers of inflammation, microbiology results, imaging

Basic clinical findings that support the presence of an infection

<2 mcg/mL and ideally <1.5 mcg/mL

Tobramycin goal trough level

By extending the dosing interval

How can you decrease the trough level without decreasing the peak for a concentration-dependent drug?

Macrobid

Brand name for nitrofurantoin

Dosed twice daily, hence the brand name MacroBID, associated with GI upset and should be taken with food, may cause the urine to turn dark yellow or brown in color, the urine discoloration is harmless, contraindicated in patients with a creatinine clearance <60 mL/min, should be taken with food to enhance absorption and decrease GI upset, only indicated for uncomplicated cystitis as serum levels are not adequate to treat systemic infections or complicated UTIs, long term use can lead to serious and fatal pulmonary toxicity

Nitrofurantoin important information

Beta-lactams

Which medications should be avoided in a patient with a history of a type 1 IgE-mediated hypersensitivity reaction to penicillin?

Staphylococcus aureus, Streptococcus pyogenes and Staphylococcus epidermidis

What organisms are likely the cause of a skin and soft tissue infection?

Pathogens differ by age but incude Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae

What organisms are likely the cause of a central nervous system infection?

Pathogens differ by respiratory tract site, but S. pneumoniae and H. influenzae are associated with both upper and lower respiratory tract infections. More resistant pathogens are associated with hospital-accquired infections

What organisms are likely the cause of a respiratory infection?

S. aureus, enterococci, Proteus spp., Viridans group streptococci

What organisms are likely the cause of a cardiovascular infection?

E. coli, Proteus spp., Klebsiella spp., enterococci, and Staphylococcus saprophyticus

What organisms are likely the cause of a urinary tract infection?

Cefazolin is an IV cephalosporin

Cefazolin formulation

No, Cefixime is not effective for enteric anaerobes

Is Cefixime effective for enteric anaerobes?

First generation

What generation cephalosporin is Cephalexin?

Third generation

What generation is Cefpodoxime?

Daptomycin (Cubicin) and linezolid (Zyvox) cover VRE (E. faecium). Nitrofurantoin is active against VRE, but should only be used for cystitis

Drugs that cover VRE

Azithromycin 250 × 2 on day 1, then 250 mg x 1 on days 2-5

Z-Pak

Telavancin has a boxed warning for fetal risk and requires a MedGuide that informs patients of the risk of fetal abnormalities

Why is it required to take a pregnancy test prior ro starting telavancin?

Ertapenem

The only agent that covers Streptococci, Gram-negative pathogens (but not pseudomonas) and anaerobes

Time-dependent killing. Therefore, maximizing the amount of time spent at a concentration above the MIC (T > MIC) correlates to optimal effectiveness of the drug’s ability to inhibit bacterial cell growth. That why they are given more frequently than concentration-dependent drugs

Pharmacodynamic properties of beta-lactams antibiotics

Primarily cleared in the liver, not the kidney, it is a MAO inhibitor (contraindicated within 2 weeks of MAO inhibitors), myelosuppression can occur with use (duration-dependent), there is a risk for serotonin syndrome if used with SSRI antidepressants (ideally, SSRI would be stopped before starting linezolid), it has excellent bioavailability, thus can transition from IV to oral formulations in a 1:1 fashion, comes in both IV and PO formulation

Linezolid important information

Bind to 50S ribosomal subunit, resulting in inhibition of RNA-dependent protein synthesis

Macrolides MOA

May prolong QT interval, blood sugar may be affected, can cause peripheral neuropathies, should be shaken prior to use, should not be administered through feeding tubes since it is oil-based and adheres to the tubing

Ciprofloxacin oral suspension important information

Cefdinir and clarithromycin

Which oral antibiotic suspensions do not require refrigeration after reconstitution?

Omnicef

Brand name for cefdinir

Quinolones decrease the seizure threshold and beta-lactams have been associated with seizures, especially if the drug accumulates

Which antimicrobial agents are associated with seizures and/or decreasing the seizure threshold?

Lipophilic, large volume of distribution, excellent tissue penetration, active against atypical pathogens (work intracellularly, rather than on the cell wall)

What pharmacokinetic characteristics do quinolones and macrolides share?

Beta-lactams and aminoglycosides

Examples of hydrophilic drugs

5:1

Ratio of sulfamethoxazole to trimethoprim

Streptococci, enterococci, Proteus spp., Escherichia coli, Klebsiella spp., and anaerobes

What organisms are likely the cause of a intra-abdominal infection?

Concentration-dependent killers active against Pseudomonas, cleared by the kidneys and associated with nephrotoxicity and ototoxicity, especially when trough levels remain high or when given for prolonged treatment courses, when used in complicated Gram-positive infections they are used for synergy, which means they must be given in combination with beta-lactams or vancomycin

Aminoglycosides important information

The minimum of microorganisms to an antibioticm inhibitory concentration is the lowest concentration of an antimicrobial drug that will inhibit the visible growth of a microorganism. Minimum inhibitory concentratinos are important to determine susceptibility of microorganisms to an antibiotic

MIC

Levofloxacin, gemifloxacin and moxifloxacin; because they have superior coverage of S. pneumoniae, a common cause of community-acquired pneumonia

Respiratory quinolones and why they are called “respiratory”

Oral vancomycin is not absorbed

Why can’t oral vancomycin be used to treat a systemic infection?

Ceftriaxone is contraindicated in neonates and can precipitate with IV calcium

Ceftriaxone contraindication

Ceftriaxone

Drug of choice for spontaneous bacterial peritonitis

Available IV only

Piperacillin/tazobactam formulations

3 g/0.375 g

Piperacillin/tazobactam dosing formulation

Beta-lactamase inhibitor that expands Zosyn’s spectrum of activity to include anaerobes and more resistant organisms

Tazobactam MOA

Zosyn

Brand name for piperacillin/tazobactam

Delfloxacin has activity against MRSA and is indicated for skin and soft tissue infections. Other quinolones should be avoided due to higher rates of resistance

Which quinolone is preferred for treatment of MRSA skin and soft tissue infections?

Binds to topoisomerase IV to inhibit DNA gyrase and the double helical coiling of the DNA

Fluoroquinolone MOA

Bactrim

Which IV antimicrobial agent is compatible with D5W only

Requires dose adjustments for CrCl <30 mL/min, associated with myopathy and rarely rhabdomyolysis, creatine kinase should be monitored weekly, only available in an IV formulation that is compatible with NS, not with dextrose

Daptomycin important information

Aztreonam, Doripenem, Levofloxacin, Tobramycin

Drugs that have activity against Pseudomonas

Cefotetan has a chemical structure (NMTT or 1-MTT side chain) that puts patients at risk for a disulfiram-like reaction if alcohol is consumed

Which cephalosporin presents a safety issue for a patient with an extensive history of alcohol abuse?

Very broad-spectrum. They cover gram positives, gram negatives, and anaerobes

Carbapenem coverage

Excellent Gram-positive coverage, including streptococci and staphylococci (MRSA), but it does not cover Pseudomonas and has no activity against gut anaerobes (Bacteroides fragilis)

Ceftaroline coverage

Can cause many CNS toxicities (including seizures) and muscle toxicities (including tendon rupture). They cause photosensitivity. They should be separated from divalent cations to avoid chelation and reduced absorption. Can cause hypoglycemia or hyperglycemia, so patients with diabetes should monitor blood glucose closely during therapy

Quinolone safety

Ceftriaxone, cefotaxime, cefdinir

Third-generation cephalosporins

Clindamycin, sulfamethoxazole/trimethoprim, linezolid

Oral medications that can be used to treat CA-MRSA

Cefotetan and cefoxitin offer an advantage over cefazolin for colorectal surgery, where B. fragilis (an anaerobic organism) is a common casue of surgical infections

Cephamycins

400-600

AUC/MIC ratio goal for vancomycin efficacy for serious MRSA infections

15-20 mcg/mL

Goal vancomycin trough for serious MRSA infections