Vancomycin and Preventing Infections - Dissertation Example

? Vancomycin Utilization to Prevent Infections Schools Number and of (e.g., July 11, 2012) Vancomycin Utilization to Prevent Infection Introduction Vancomycin is a glycopeptide antibiotic that has bactericidal properties against gram-positive bacteria but not gram-negative bacteria (Corey et al., 2012; Ouelette & Joyce, 2010). It is used to treat infections caused by most staphylococci, including the strains that are resistant to methicillin (MRSA – Methicillin Resistant Staphylococcus aureus), nafcillin, and penicillin (Ouelette & Joyce, 2010). Vancomycin was isolated from Amycolatopsis orientalis (Corey et al., 2012). The emergence of multi-drug resistant strains of bacteria in the 1960s led to widespread research in antibiotics that could be effective against drug resistant strains. Vancomycin emerged to be one of the rare antibiotics that could be used against such multi-drug resistant bacteria (Corey et al., 2012). The action of the antibiotic is slow as it only acts against actively dividing cells. The structure of the vancomycin molecule is closely related to that of teicoplanin and has heptapeptide scaffolds linked to both amino-sugar and sugar moieties. Both vancomycin and teicoplanin are only used as a last resort for treating life-threatening infections by multi-drug resistant bacteria such as MRSA (Ouelette & Joyce, 2010). The emergence of bacterial resistance to vancomycin in the recent years has led to restrictions in its use. The drug may cause hypersensitivity reactions. Very rapid administration of vancomycin leads to urticarial/erythematous reactions, flushing, hypotension, tachychardia, etc. leading to a syndrome called the ‘red man’ syndrome (Ouelette & Joyce, 2010). This syndrome, however, is not an allergic reaction but is rather caused due to the toxic effect of the drug on mast cells. Mechanism of Action of Vancomycin Vancomycin, like several other glycopeptides, inhibits one of the stages of peptidoglycan synthesis in bacteria (Reynolds, 1989). It is a tricyclic glycopeptide molecule and binds to precursor units in cell wall synthesis (Ouelette & Joyce, 2010). It functions by inhibiting the action of transglycosylase and transpeptidase, which subsequently leads to the prevention of elongation and cross-linking of PG (peptidoglycan), thereby making the bacterial cell vulnerable to lysis. Fig. 1: Tricyclic glycopeptide structure of vancomycin (Ouelette & Joyce, 2010, p. 207) The three-dimensional structure of vancomycin forms a cleft that allows it to bind to late stage PG intermediates that have a D-alanyl-D-alanine terminus (Corey et al., 2012). Vancomycin is selectively toxic since the sequences L-aa-D-aa-D-aa of the peptide PG intermediates are only found in the cell walls of bacteria. Fig. 2: Figure showing the PG intermediates and vancomycin with its cleft where it binds to the D-Ala-D-Ala terminus (Corey et al., 2012, p. 138) Hydrogen bonding between the vancomycin glycopeptide molecule and the peptides of PG intermediates results in the formation of stable complexes (Reynolds, 1989). This in turn leads to the inhibition of transglycosylation and transpeptidation reactions by two important enzymes as they fail to bind to the terminus due to steric hindrance. Because of this, the elongation of the glycan chain is inhibited. The mechanism of action of vancomycin thus involves the binding of a “bulky inhibitor” (vancomycin) to the substrate (D-alanyl-D-alanine terminus) outside the cell membrane because of which the active site of two bacterial enzymes (transglycosylase and transpeptidase) cannot align and bind to the substrate. This unique mechanism of action of vancomycin renders drug resistance by most bacteria difficult, unlike most other antibiotics (Reynolds, 1989). Vancomycin Usage Vancomycin is used to treat severe infections such as pneumonia, endocarditis, abscesses, and empyema caused by MRSA, and also for the treatment of patients allergic to cephalosporins and penicillins (Ouelette & Joyce, 2010). If a patient is allergic to penicillins and cephalosporins, drugs such as vancomycin are usually the only resort because allergic reactions to vancomycin are rare (Ouelette & Joyce, 2010). It is useful for most infections that occur anywhere in the body and are caused by gram-positive bacteria, but is ineffective in case of viral infections such as cold and flu as the antibiotic acts only against bacteria and not viruses. It is also used in combination with other drugs such as rifampin and cefotaxime in patients with pneumococcal meningitis that is resistant to penicillin (Ouelette & Joyce, 2010). Enterocolitis is also sometimes treated using vancomycin in case metronidazole becomes ineffective (Ouelette & Joyce, 2010). It is also used as a prophylactic for patients implanted with prosthetics such as artificial heart valves in order to prevent infections. Patients with cardiac surgeries, prosthetic implants, dental work or surgeries of the respiratory tract are highly susceptible to bacterial endocarditis, which is associated with high rates of morbidity and mortality (Dajani et al., 1990). Endocarditis is usually caused by staphylococci and diphtheroids. Treatment with a single antibiotic is often ineffective. Moreover, the use of broad-spectrum antibiotics over long periods of time may result in superinfection with drug resistant microorganisms (Dajani et al., 1990). Therefore, perioperative prophylaxis using vancomycin is often indicated (Dajani et al., 1990). Vancomycin is available for clinical use in the form of vancomycin hydrochloride for intravenous and oral use (Nightingale, Murakawa, and Ambrose, 2001). Treatment using vancomycin is supposed to be limited to only those cases where other antibiotics are contraindicated due to allergy or drug resistance. Vancomycin Resistance Vancomycin binds to the PG D-alanyl-D-alanyl terminus through five hydrogen bonds. However, certain bacterial strains have acquired D-alanyl-D-lactate terminus instead of the usual D-alanyl-D-alanyl terminus. In this case, vancomycin can only bind through four hydrogen bonds to the modified terminus. The potency of the antibiotic in this case is reduced 1000 fold, leading to the emergence of vancomycin resistant bacteria (Corey et al., 2012). Some strains of enterococci, especially E. faecalis and E. faecium have become resistant to vancomycin. Several strains of Lactobacillus, Leuconostoc, and Pediococcus have also been found to have developed vancomycin resistance (Swenson, Facklam, and Thornsberry, 1990). Various strains of Staphylococcus aureus have also acquired vancomycin resistance. The emergence of VRE (vancomycin resistant enterococci) was first reported in 1988 (Robinson, Feil, and Falush, 2010). Nosocomial infections with VRE became highly prevalent. Within 15 years, healthcare infections by VRE rose from 0% to 80% in case of E. faecium (Robinson, Feil, and Falush, 2010). Between the years 1999 and 2005, the percentage of enterococci that were vancomycin resistant rose by 2.8 fold (Robinson, Feil, and Falush, 2010). VRE spread across the world at a rapid rate. Seven types of vancomycin resistance are now reported, namely vanA, vanB, vanC, vanD, vanE, vanG, and vanL. These are based on the bacterial genes that cause vancomycin resistance. Vancomcyin resistance genes can be transmitted via plasmids to other non-resistant bacteria, conferring them with vancomycin resistance (Gillespie, 2004). Transfer of vancomycin resistance from enterococci to staphylococci has been demonstrated in the laboratory (Gillespie, 2004). Invivo spread to other bacteria such as corynebacterium has also been reported. Staphylococcus aureus is associated with many nosocomial infections. While MRSA has raised widespread concern over the treatment of severe infections, the incidence of vancomycin resistant Staphylococcus aureus (VRSA) and vancomycin intermediate Staphylococcus aureus (VISA) has also increased dramatically. Many MRSA strains that could be killed using only vancomycin have started showing resistance to vancomycin (Khan, 2009). MRSA strains showing intermediate resistance to vancomycin are termed VISA (Khan, 2009). VISA and VRSA were both first reported in the United States and later on from several other countries especially those in Europe (Khan, 2009). Clearinghouse Standards and Guidelines for the Use of Vancomycin (500) The recommendations for adults provided by National Clearinghouse (2011) for vancomycin dosing and monitoring are based on seven principles. These guidelines are based on American Society of Health System Pharmacists, Institute for Defence Studies and Analyses (IDSA), and The Society of Infectious Diseases Pharmacists (National Clearinghouse, 2011). 1) Vancomycin given intravenously is 15-20 mg/kg/dose q 8-12 hours in patients with normal renal function, and should not exceed more than 2 grams per dose. 2) A loading dose for patients with sepsis, endocarditis, pneumonia, meningitis or with suspected MRSA of 25-30 mg/kg/dose may be effective, due to risk of RMS and anaphylaxis risk consideration is given to prolonging infusion time and use of an antihistamine. 3) Troughs at fourth or fifth dose with the peak concentrations not recommended. 4) Troughs of 15-20 mcg/mL are recommended for patients with meningitis, bacteremia, osteomyelitis, necrotizing fasciitis, pneumonia, and endocarditis. 5) Trough monitoring is not required for patients with necrotizing fasciitis who are not obese with normal renal function. 6) Trough monitoring for those with renal impairment, especially dialysis patients, morbidly obese, or fluctuating distribution of volume recommended. 7) Continuous infusion rates are not recommended. Therapeutic drug monitoring relates to the evaluation of the efficacy and toxicity of a drug. The concentrations of the drug above the range (peak) can be toxic and those below the range (trough) can be ineffective (Siemens Healthcare Diagnostics Inc. 2009). The peak for vancomycin is 30 – 40 mg/mL and trough is 5 – 10 mg/mL (Siemens Healthcare Diagnostics Inc. 2009). The peak levels of vancomycin are not associated with drug efficacy or toxicity. Rather, trough values are regularly monitored to make sure that the serum concentration of the drug stays above the minimum inhibitory concentration (MIC) of the bacteria (Siemens Healthcare Diagnostics Inc. 2009). It is sometimes recommended that the peak concentrations of vancomycin should be maintained under 50 mg/L in order to prevent ototoxicity (Lee, 2009). While most hospitals routinely monitor vancomycin in all patients, its monitoring in normal patients with optimal renal function is often questioned (Lee, 2009). Patients with altered or decreased renal function, those being administered ototoxic or nephrotoxic drugs, etc should be regularly monitored. The elimination of vancomycin is linear and the trough concentration changes in proportion to the dosage concentration (Lee, 2009). The dosage of vancomycin has considerably changed over the years because of the introduction of new technologies and changes in practice patterns (Pallotta and Manley, 2008). The changes in dosing have occurred because of the emergence of drug resistance, changes in nephrotoxicity, etc (Thomson et al, 2009). Vancomycin has been the antibiotic of choice for dialysis patients for the prevention of infections with gram-positive bacteria (Vandecasteele and De Vriese, 2011). The dosage has dramatically changed for hemodialysis patients. This is because of changes in reprocessing practices, creation of high flux hemodialysis filters, and emergence of drug resistant bacteria (Pallotta and Manley, 2008). The dosage of vancomycin in hemodialysis patients depends on the timing of drug administration during or after the performance of dialysis, the type of filter and the duration of dialysis (Vandecasteele and De Vriese, 2011). Historically, many have assumed that obese patients have increased clearance levels proportionally with total body weight, which is based from the correlation with increased blood volume, organ size, and adipose tissue. Reynolds, White, Alexander, and Deryke (2012) demonstrated an analysis for dosing regimen for obese patients compared to adult patients with normal renal function. Their findings suggested that obese patients demonstrated increased vancomycin volume distribution, but not to the same degree of clearance. For instance, if one obese and one average weight patient were to receive a similar dose, vancomycin is dosed based from total body weight, the vancomycin trough concentration would be decreased in the obese patient. Reynolds, White, Alexander, and Deryke (2012) explain that this variable could be the increase in vancomycin volume distribution and the related under-appreciation. Vance-Bryan et al. (1993) also performed a study which found the average body weight percentage over lean body weight were separate entities which revealed the finding that vancomycin is based from the volume distribution principal. Intravenous administration of vancomycin has several side effects, the most common of which is the red man syndrome (Root, 1999). This is mediated by the release of histamine upon mast cell damage caused by rapid administration of the drug. Nephrotoxicity by vancomycin is rare when it is administered singly. However, when given along with aminoglycosides, the occurrence of nephrotoxicity becomes common (Root, 1999). High serum levels of vancomycin along with aminoglycoside usage is also found to increase the incidence of ototoxicity. A common hematologic side effect of the drug is reversible neutropenia (Root, 1999). Vancomycin is used in conjunction with other antibiotics such as aminoglycosides to increase the spectrum of coverage over the maximum number of gram-positive bacteria possible. Best Practices for Health Personnel Healthcare institutions seek best practices for the prevention of vancomycin resistance. Innumerable studies have shown that vancomycin when used incorrectly can lead to resistance. Healthcare facilities are now screening people for VRE and VRSA when needed, instead of just MRSA. In order to prevent the emergence of vancomycin resistant bacteria and to prevent nosocomial infections from the same, it is imperative to increase knowledge of vancomycin administration guidelines and to ensure proper use of PPE (Personal protective equipment). For the development of efficient guidelines for vancomycin usage, the participation of a health facility’s pharmacists, epidemiologists, the infection control departments, the pathologists, the medical and the surgical staff, microbiology laboratories, etc should be encouraged. It is to be noted that nurses are the last line of defense for medication administration throughout medicine, and it is important for nurses to understand the proper treatment options, healthcare status of the individual, and the use of vancomycin. There are several insinuations for nurses from the above review and the resultant recommendations made for appropriate usage of vancomycin. Healthcare professionals should be educated well with regards to knowing the proper use of vancomycin (for gram positive bacteria) or why it is used as a prophylaxis to prevent infection as well as its mechanism of action and how it should start in orientation and as annual competency. The compliance of staff with guidelines pertaining to handling patients infected with VRE, VRSA and VISA should be regularly monitored. Proper compliance with PPE (gown, gloves, etc) and other hygienic practices such as hand-washing should be ensured to the prevent spread of vancomycin resitant strains. When lobby privileges are awarded to some patients, which includes patients with resistant organisms that can lead to the risk of transmitting the bacteria to other individuals, maintenance of proper PPE should be ensured. Nurses should only use vancomycin in appropriate or acceptable situations. For instance, vancomycin could be less bactericidal if used to treat infections caused by beta-lactam- resistant gram-positive microorganisms. In such situations, it is advisable that nurses use beta-lactam agents for beta-lactam-susceptible Staphylococci. Nurses are also advised to use vancomycin to prevent infections caused by gram-positive microorganisms in patients that are hypersensitive to beta-lactam antimicrobials. Routine surgical prophylaxis is another element in which vancomycin use is discouraged. The exceptions to this condition are patients with life-threatening allergies to beta-lactam antibiotics. In addition, vancomycin should not be used for imagined infections in patients with cultures that are negative for beta-lactam-resistant gram-positive microorganisms (The Arizona Department of Health Services, 1999). The CDC (Centers for Disease Control and Prevention) has released guidelines for the appropriate and inappropriate use of vancomycin. The appropriate uses include treatment of severe infections that are caused by beta-lactam resistant bacteria, treatment of patients with beta-lactam allergies, treatment of colitis upon failure of metronidazole, prophylaxis of endocarditis, and prophylaxis for those implanted with prosthetics at health institutions with high incidence of MRSA (Nightingale, Murakawa, and Ambrose, 2001). The inappropriate uses of vancomycin include use for prophylaxis in routine surgeries, treatment of patients with febrile neutropenia without evidence of the presence of gram-positive bacterial infection, treatment based on a single positive blood culture result for coagulase negative staphylococci while all other cultures from the same time frame are negative, continued administration of the drug without confirming the presence of beta-lactam resistant gram positive bacteria, prophylaxis for catheter use, selective decontamination of gut, eradication of MRSA colonization, primary mode of treatment of colitis associated with antibiotic therapy, routine prophylaxis for chronic ambulatory peritoneal dialysis patients and infants with low birth weight, and topical application of the drug (Nightingale, Murakawa, and Ambrose, 2001). Significant information exists for vancomycin use in the hospital setting, but not so much for outpatient and use in the community setting. Challenges to proper usage of vancomycin may be caused due to lack of patient education, minimal studies in relation to patient education and improper compliance with best practice guidelines. Healthcare workers can sometimes lack proper understanding on correct dosage for patients. After extensive literature review, it is clear that improper preventive application or incorrect utilization of vancomycin may lead to the increased incidence of vancomycin resistant bacteria. It is thus imperative for healthcare institutions, healthcare workers and patients to comply with best practices regarding treatment with vancomycin as it is one of the few remaining antibiotics that can be used for the treatment of infections with multiple drug resistant bacteria or in patients with allergies to other common antibacterial agents. References Corey, E. J., Czako, B., & Kurti, L. (2012). Molecules and Medicine. Hoboken, NJ: John Wiley & Sons. Dajani, A. S., Bisno, A. L., Chung, K. J., Durack, D. T. et al. (1990). Prevention of Bacterial Endocarditis: Recommendations by the American Heart Association. The Journal of American Medical Association, 264(22), 2919-2922. Gillespie, S. H. (2004). Management of Multiple Drug-Resistant Infections. Totowa, NJ: Humana Press. Khan, A. U. (2009). Current Trends In Antibiotic Resistance In Infectious Diseases. New Delhi: I. K. International Pvt Ltd. Lee, M. (2009). Basic Skills in Interpreting Laboratory Data. Bethesda, MD: ASHP. National Clearinghouse. (2011). Guidelines. Retrieved on 8 July from http://guidelines.gov/browse/archive.aspx?type=1 Nightingale, C. H., Murakawa, T., & Ambrose, P. G. (2001). Antimicrobial Pharmacodynamics in Theory and Clinical Practice. New York, NY: CRC Press. Ouellette, R. G., & Joyce, J. A. (2010). Pharmacology for Nurse Anesthesiology. Sudbury: MA: Jones & Bartlett Publishers. Pallotta, K. E., & Manley, H. J. (2008). Vancomycin use in patients requiring hemodialysis: a literature review. Seminars in Dialysis, 21(1), 63-70. Reynolds, P. E. (1989). Structure, biochemistry and mechanism of action of glycopeptide antibiotics. European Journal of Clinical Microbiology & Infectious Diseases, 8(11), 943-950. Robinson, D. A., Feil, E. J., & Falush, D. (2010). Bacterial Population Genetics in Infectious Disease. Hoboken, NJ: John Wiley & Sons. Root, R. K. (1999). Clinical Infectious Diseases: A Practical Approach. New York, NY: Oxford University Press. Siemens Healthcare Diagnostics Inc. (2009). Therapeutic Drug Monitoring (TDM) An Educational Guide. Deerfield, IL: Siemens Healthcare Diagnostics Inc. Retrieved on 8 July from http://www.medical.siemens.com/siemens/en_GLOBAL/gg_diag_FBAs/files/products_disease_states/TDM/TDM_Guide_FINAL.pdf Swenson, J. M., Facklam, R. R., & Thornsberry, C. (1990). Antimicrobial susceptibility of vancomycin-resistant Leuconostoc, Pediococcus, and Lactobacillus species. Antimicrobial Agents Chemotherapy, 34(4), 543–549. The Arizona Department of Health Services. (July, 1999). Guidelines for the management of patients with antibiotic-resistant organisms. Retrieved on 8 July from http://azdhs.gov/phs/oids/hai/documents/ADHS_GuidelinesPatientsWithAntibioticResistantOrganisms.pdf Thomson, A. H., Staatz, C. E., Tobin, C. M., Gall, M., & Lovering, A. M. (2009). Development and evaluation of vancomycin dosage guidelines designed to achieve new target concentrations. Journal of Antimicrobrial Chemotherapy, 63(5), 1050-1057. Vandecasteele, S. J., & De Vriese, A. S. (2011). Vancomycin Dosing in Patients on Intermittent Hemodialysis. Seminars in Dialysis, 24 (1), 50–55. Read More