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Vancomycin is a glycopeptide antibiotic medication used to treat a number of bacterial infections. It is recommended intravenously as a treatment for complicated skin infections, bloodstream infections, endocarditis, bone and joint infections, and meningitis caused by methicillin-resistant ''Staphylococcus aureus''. Blood levels may be measured to determine the correct dose. Vancomycin is also taken by mouth as a treatment for severe ''Clostridium difficile'' colitis. When taken by mouth it is poorly absorbed.

Common side effects include pain in the area of injection and allergic reactions. Occasionally, hearing loss, low blood pressure, or bone marrow suppression occur. Safety in pregnancy is not clear, but no evidence of harm has been found, and it is likely safe for use when breastfeeding. It is a type of glycopeptide antibiotic and works by blocking the construction of a cell wall.

Vancomycin was approved for medical use in the United States in 1958. It is on the World Health Organization's List of Essential Medicines. The World Health Organization classifies vancomycin as critically important for human medicine. It is available as a generic medication. Vancomycin is made by the soil bacterium ''Amycolatopsis orientalis''.

Medical uses

Vancomycin is indicated for the treatment of serious, life-threatening infections by Gram-positive bacteria unresponsive to other antibiotics.

The increasing emergence of vancomycin-resistant enterococci has resulted in the development of guidelines for use by the Centers for Disease Control Hospital Infection Control Practices Advisory Committee. These guidelines restrict use of vancomycin to these indications:
* Treatment of serious infections caused by susceptible organisms resistant to penicillins (methicillin-resistant ''S. aureus'' (MRSA) and multidrug-resistant ''S. epidermidis'' (MRSE)) or in individuals with serious allergy to penicillins''
* Treatment of pseudomembranous colitis caused by ''C. difficile''; in particular, in cases of relapse or where the infection is unresponsive to metronidazole treatment (for this indication, vancomycin is given orally, rather than by its typical intravenous route)
* For treatment of infections caused by Gram-positive microorganisms in patients with serious allergies to beta-lactam antimicrobials.
* Antibacterial prophylaxis for endocarditis following certain procedures in penicillin- hypersensitive individuals at high risk
* Surgical prophylaxis for major procedures involving implantation of prostheses in institutions with a high rate of MRSA or MRSE
* Early in treatment as an empiric antibiotic for possible MRSA infection while waiting for culture identification of the infecting organism
*Halting the progression of primary sclerosing cholangitis and preventing symptoms; vancomycin does not cure the patient and success is limited
* Treatment of endophthalmitis by intravitreal injection for gram-positive bacteria coverage. It use to prevent the condition, however, is not recommended due to the risk of side effects.

Spectrum of susceptibility

Vancomycin is considered a last resort medication for the treatment of sepsis and lower respiratory tract, skin, and bone infections caused by Gram-positive bacteria. The minimum inhibitory concentration susceptibility data for a few medically significant bacteria are:
* ''S. aureus'': 0.25 μg/mL to 4.0 μg/mL
* ''S. aureus'' (methicillin resistant or MRSA): 1 μg/mL to 138 μg/mL
* ''S. epidermidis'': ≤0.12 μg/mL to 6.25 μg/mL

Side effects

Serum vancomycin levels may be monitored in an effort to reduce side effects, although the value of such monitoring has been questioned. Peak and trough levels are usually monitored, and for research purposes, the area under the concentration curve is also sometimes used. Toxicity is best monitored by looking at trough values.

Common adverse drug reactions (≥1% of patients) associated with IV vancomycin include: local pain, which may be severe, and thrombophlebitis.

Damage to the kidneys ( nephrotoxicity) and to the hearing ( ototoxicity) were side effects of the early impure versions of vancomycin, and these were prominent in the clinical trials conducted in the mid-1950s. Later trials using purer forms of vancomycin found nephrotoxicity is an infrequent adverse effect (0.1% to 1% of patients), but this is accentuated in the presence of aminoglycosides.

Rare adverse effects (<0.1% of patients) include: anaphylaxis, toxic epidermal necrolysis, erythema multiforme, red man syndrome, superinfection, thrombocytopenia, neutropenia, leukopenia, tinnitus, dizziness and/or ototoxicity, and DRESS syndrome.

Vancomycin can induce platelet-reactive antibodies in the patient, leading to severe thrombocytopenia and bleeding with florid petechial hemorrhages, ecchymoses, and wet purpura.

Historically, vancomycin has been considered a nephrotoxic and ototoxic drug, based on numerous case reports in the medical literature following initial approval by the FDA in 1958. However, as the use of vancomycin increased with the spread of MRSA beginning in the 1970s, toxicity risks were reassessed. With the removal of impurities present in earlier formulations of the drug
, and with the introduction of therapeutic drug monitoring, the risk for severe toxicity has been reduced.

Nephrotoxicity

The extent of nephrotoxicity for vancomycin remains controversial. In 1980s, vancomycin with a purity > 90% was available, and kidney toxicity defined by an increase in serum creatinine of at least 0.5 mg/dl, occurred in only about 5% of patients. However, dosing guidelines from the 1980s until 2008 recommended vancomycin trough concentrations between 5 and 15 μg/ml. Concern for treatment failures prompted recoomendations for higher dosing (troughs 15 to 20 μg/ml) for serious infection, and acute kidney injury (AKI) rates attributable to the vancomycin increased.

Importantly, the risk of AKI increases with co-administration of other known nephrotoxins, in particular, aminoglycosides. Furthmore, the sort of infections treated with vancomycin may also cause AKI and sepsis is the most common cause of AKI in critically ill patients. Finally, studies in humans are mainly associations studies where the cause of AKI is usually multifacotorial.

Animal studies have demonstrated that higher doses and longer duration of vancomycin exposure correlates with increased histopathologic damage and elevations in urinary biomarkers of AKI.37-38 Damage is most prevalent at the proximal tubule, which is further supported by urinary biomarkers, such as kidney injury molecule-1 (KIM-1), clusterin, and osteopontin (OPN),
and in humans, insulin-like growth factor binding protein 7 (IGFBP7) as part of the nephrocheck test.

The mechanisms that underlie the pathogenesis of vancomycin nephrotoxicity are multifactorial but include interstitial nephritis, tubular injury due to oxidative stress, and cast formation.

Ototoxicity

Attempts to establish rates of vancomycin-induced ototoxicity are even more difficult due to the scarcity of quality evidence. The current consensus is that clearly related cases of vancomycin ototoxicity are rare. The association between vancomycin serum levels and ototoxicity is also uncertain. While cases of ototoxicity have been reported in patients whose vancomycin serum level exceeded 80 µg/mL, cases have been reported in patients with therapeutic levels, as well. Thus, whether therapeutic drug monitoring of vancomycin for the purpose of maintaining "therapeutic" levels will prevent ototoxicity also remains unproven.

Interactions with other nephrotoxins

Another area of controversy and uncertainty concerns the question of whether, and if so, to what extent, vancomycin increases the toxicity of other nephrotoxins. Clinical studies have yielded variable results, but animal models indicate some increased nephrotoxic effect probably occurs when vancomycin is added to nephrotoxins such as aminoglycosides. However, a dose- or serum level-effect relationship has not been established.

Dosing considerations

The recommended parenteral dosage in adults is 500 mg iv every 6 hours or 1000 mg every 12 hours, with modification to achieve a therapeutic range as needed. The recommended oral dosage in the treatment of antibiotic induced pseudomembranous enterocolitis is 125 to 500 mg every 6 hours for 7 to 10 days. Text was copied from this source, which is available under
Creative Commons Attribution 4.0 International License

Intravenous vs oral administration

Vancomycin must be given intravenously (IV) for systemic therapy, since it is not absorbed from the intestine. It is a large hydrophilic molecule that partitions poorly across the gastrointestinal mucosa. Due to short half-life, it is often injected twice daily.

The only approved indication for oral vancomycin therapy is in the treatment of pseudomembranous colitis, where it must be given orally to reach the site of infection in the colon. Following oral administration, the fecal concentration of vancomycin is around 500 µg/mL (sensitive strains of ''C. difficile'' have a mean inhibitory concentration of ≤2 µg/mL)

Inhaled vancomycin has also been used (off-label), via nebulizer, for treatment of various infections of the upper and lower respiratory tract.

There is an ongoing debate as to whether vancomycin should be given through a central or peripheral line. According to a 2014 review, midline catheters are a safe option for administration.

Vancomycin Flushing Reaction (aka "Red man syndrome")

Vancomycin is recommended to be administered in a dilute solution slowly, over at least 60 min (maximum rate of 10 mg/min for doses >500 mg) due to the high incidence of pain and thrombophlebitis and to avoid an infusion reaction known as vancomycin flushing reaction. This phenomenon has been often clinically referred to as "red man syndrome". The reaction usually appears within 4 to 10 min after the commencement or soon after the completion of an infusion and is characterized by flushing and/or an erythematous rash that affects the face, neck, and upper torso, attributed due to release of histamine from the mast cells. These findings are due to interaction of vancomycin with MRGPRX2, a GPCR mediating IgE-independent mast cell degranulation. Less frequently, hypotension and angioedema may also occur. Symptoms may be treated or prevented with antihistamines, including diphenhydramine, and are less likely to occur with slow infusion.

Therapeutic drug monitoring

Plasma level monitoring of vancomycin is necessary due to the drug's biexponential distribution, intermediate hydrophilicity, and potential for ototoxicity and nephrotoxicity, especially in populations with poor renal function and/or increased propensity to bacterial infection. Vancomycin activity is considered to be time-dependent; that is, antimicrobial activity depends on the duration that the serum drug concentration exceeds the minimum inhibitory concentration of the target organism. Thus, peak serum levels have not been shown to correlate with efficacy or toxicity; indeed, concentration monitoring is unnecessary in most cases. Circumstances in which therapeutic drug monitoring is warranted include: patients receiving concomitant aminoglycoside therapy, patients with (potentially) altered pharmacokinetic parameters, patients on haemodialysis, patients administered high-dose or prolonged treatment, and patients with impaired renal function. In such cases, trough concentrations are measured.

Target ranges for serum vancomycin concentrations have changed over the years. Early authors suggested peak levels of 30 to 40 mg/L and trough levels

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