![]() Reduces tissue penetration (only free drug is able to leave the bloodstream and penetrate tissues).Reduces renal clearance (only free drug is cleared).Creates a reservoir of drug which is bound to albumin (which may extend the drug's half-life).A high percent protein binding (>90%) may have the following consequences:.Only unbound drug is active against bacteria. Protein binding refers to the percent of drug in the blood which is bound to albumin.A recent analysis of over fifty RCTs found no benefit of cidal antibiotics compared to static antibiotics, so the clinical superiority of cidal antibiotics may be mostly mythological.Just because an antibiotic is bacteriostatic doesn't mean that it's not extremely effective. In some situations this may be important, but other factors may be equally if not more important (e.g. Overall, the focus on cidality is probably misplaced.Severe neutropenia is one situation where the petri-dish model may actually be accurate, so cidal antibiotics might be desirable in that context.However, this model isn't very accurate – in vivo, the antibiotic is just assisting the patient's immune system in containing the infection. The concept that bactericidal antibiotics are superior is based on a petri-dish model of infectious disease, wherein the antibiotic is relied upon to kill the bacteria.They are used specifically for this reason – to shut down toxin synthesis (rather than necessarily immediately destroying all the bacteria). clindamycin and linezolid) cause immediate cessation of toxin secretion in patients with toxic shock. For example: Antibiotics which inhibit protein synthesis (e.g.endotoxin) causing uncontrolled inflammation. However, cidality may actually be dangerous if this leads to rapid lysis of bacteria leading to a huge release of bacterial products (e.g. Traditionally it was believed that cidality was desirable for severe infections.An antibiotic which is bactericidal kills bacteria, whereas an antibiotic which is bacterio static stops bacteria from dividing.Urinary drug concentrations depend on serum level, percent excreted in the urine, and how concentrated the urine is.Likewise, excretion of unchanged drug in the bile is ideal for biliary or intestinal infections. Excretion of unchanged drug in the urine is ideal for treatment of urinary tract infections, because this will often produce very high drug concentrations in the kidney and bladder. ![]() Hepatic metabolism/excretion is generally convenient, because this means the drug dose doesn't need to be adjusted based on renal function.Antibiotics may be metabolized in the liver (often into inactive metabolites) or they may be excreted unchanged in the urine or bile.Specific properties of various antibiotics Requirement for surgical/percutaneous drainage.volume overload, superinfection at different site, drug fever) Development of a new hospital-related problem (e.g.Common causes of treatment failure include:.If a patient is failing antibiotic therapy, broadening coverage is usually not the answer.Use of procalcitonin has been shown to limit antibiotic exposure, while possibly improving patient outcomes.Have some sort of plan regarding when to discontinue antibiotics and follow it. Keep track in your notes of how long the patient has been on each antibiotic.Try to choose antibiotics that cover pathogens that the patient has grown in the recent past. Review which antibiotics patient has been exposed to recently try to avoid these if possible.Septic patients may have increased drug clearance, so antibiotics should generally be dosed on the higher end of dose ranges.If possible, get cultures before starting antibiotics.Don't treat colonization except in very specific situations (e.g. Colonization commonly occurs in the bladder of anuric or catheterized patients, or sputum of intubated patients. A positive culture may represent infection or colonization (bacteria present without causing disease).Antibiotics shouldn't be started blindly (without a defined source of infection) unless the patient has septic shock or neutropenic fever.Patients are critically ill, so we're justified in using broad-spectrum agents initially. cefepimeĪntibiotics in the ICU are in some ways simpler than antibiotic therapy for less ill patients. □ Drug-resistant gram positive cocci: vancomycin vs.Some common antibiotic selection debates:.Extended-spectrum beta-lactamases (ESBL).Drug-resistant organisms of particular importance.Macrolides (Azithromycin, Clarithromycin).General considerations for antibiotic therapy.
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