* Respiratory fluoroquinolones including levofloxacin, moxifloxacin, and gatifloxacin have increased activity against gram-positive bacteria (particularly S. pneumoniae) compared to older quinolones such as ciprofloxacin.
* In the United States, about 40% of S. pneumoniae are not susceptible to penicillin, and 40% of these meet the laboratory criteria for resistance.
* Penicillin-resistant S. pneumoniae tend to show laboratory resistance to a number of other antibiotic classes.
* In the United States, 25%-30% of macrolide resistant S. pneumoniae are erm+; 70-75% are mef+.
* Methicillin resistant S. aureus (MRSA) also tend to be quinolone resistant.
* 10 to 40% of Haemophilus influenzae are ampicillin resistant.
* 40 to 80% of Staphylococcus epidermidis are methicillin resistant (MRSE).
* 5 to 50% of Staphylococcus aureus are methicillin resistant (MRSA).
* Almost all staphylococci are penicillinase producing.
* Enterococcus is preferably treated with a combination of penicillin or ampicillin or vancomycin plus either streptomycin or gentamicin when a systemic infection is suspected. Multiple antibiotic resistant enterococci are becoming much more common and traditional therapeutic approaches will usually not work for these organisms.
* Vancomycin is the drug-of-choice for methicillin-resistant Staphylococcus epidermidis (MRSE) and Staphylococcus aureus (MRSA).
* No currently marketed cephalosporin should be used to treat methicillin resistant staphylococcal infections.
* No currently marketed cephalosporin should be used to treat enterococcal infections.
* First and second generation cephalosporins do not provide adequate coverage for Pseudomonas aeruginosa.
* Of the cephalosporins only ceftazidime and cefepime provide reasonable coverage for Pseudomonas aeruginosa infections. (Although these drugs may represent the cephalosporins of choice of Pseudomonas infections they may not be the drug of choice of Pseudomonas infections.
* Only some select third generation cephalosporins should be considered for treating meningeal infections (Selection of third generation cephalosporins should be based on the likely microorganism and penetration into cerebrospinal fluid and their CSF MIC.
* Cefamandole, cefoperazone, and cefotetan are the only cephalosporins with a 3-methylthiotetrazole substitution.
* The 3-methylthiotetrazole substitution is likely responsible for both the coagulation problems observed with cephalosporins and the disulfiram reaction.
* Of the currently marketed cephalosporins only cefoxitin, cefotetan, and possibly ceftizoxime should be considered as adequate coverage for Bacteroides fragilis infections.
* Of the currently available cephalosporins, only cefoxitin, cefotaxime, ceftriaxone and possibly some of the other third generation cephalosporins should be considered for penicillinase producing Neisseria gonorrhea infections.
* No currently marketed cephalosporins should be considered as adequate therapy for Listeria infections especially central nervous system infections.
* The need for totally empiric or "blind" therapy is rare.
* The likely source of infection is a strong indicator of the likely cause of infection.
* The causes of community-acquired infection are different from the causes of hospital-acquired infection.
* The sources and causes of infection are more diverse in immunosuppressed patients than in normal hosts.
* Signs and symptoms of infection are more subtle and obscure in immunosuppressed patients.
* All empiric therapy regimens should be modified to a regimen appropriate for the susceptibility of the causative agent(s) once known.
* Antibiotic regimens should be the least toxic that is appropriate to the causative agent.
* The sicker the patient, the greater the need for immediate antimicrobial treatment.
* Neutropenic patients (100/mm3) require immediate institution of antimicrobial therapy if they appear to have infection.
* Infections of specialized body sites require special antimicrobial consideration (e.g. meningitis require high penicillin dosage to achieve adequate CSF levels endocarditis requires prolonged high dose therapy to prevent relapse).
* With a first order PK drug, an increase or decrease in dose will result in a proportional increase or decrease in serum concentrations.
* The time between the peak and the trough of an antibiotic given intravenously is T-t'.
* Ko is an infusion rate and not a dose. Dose is equal to Ko x t'.
* With a first order drug, half-life and Kd are dose independent parameters. Any factor that prevents the patient from receiving the assumed dose of aminoglycoside will not change the determination of t1/2 or Kd.
* Any factor that prevents the patient from receiving the assumed amount of aminoglycoside will result in an error in the calculation of distribution volume.
* Trough concentration drawn prior to the intravenous administration of an antibiotic must be extrapolated to the start of the antibiotic infusion.
* With aminoglycoside trough/peak checks, the trough concentration is used both in the calculation of Kd and in the calculation of volume of distribution at steady-state. Whereas with first- or second-dose kinetics the trough is used only in the calculation of volume of distribution.
* To accurately perform trough/peak pharmacokinetic studies, the patient must be at steady-state using the same dose, dosage interval, and infusion time while on the same schedule. The patient also must have received the drug for at least 5 half-lives and the clinical status (serum creatinine and fluid status etc.) are not undergoing dramatic change.
* An aminoglycoside dosage interval usually approximates two or three patient drug half-lives.
* The elimination rate constant, half-life, and distribution volume are similar between aminoglycosides (except for inactivation with beta-lactam antibiotics) i.e. pharmacokinetic data from one aminoglycoside can be used to develop a dosage and dosage interval for another aminoglycoside.