Staphylococcus aureus is a Gram-positive bacteria that colonises the tegument and can be found in the anterior nares in about 25-30 % of healthy persons. Meticillin-resistant of Staphylococcus aureu was isolated in the twelvemonth 1961 in UK, half a twelvemonth after the debut of meticillin into the community. It became one of the most prevailing bacteriums globally that causes an infection and it besides resists other members in the beta-lactam antibiotic category, including penicillins, Mefoxins and carbapenems. Vancomycin has been used as the standard intervention of MRSA infection in the past 50 old ages. However, MICs are by and large lifting as a consequence of opposition development which led to a diminution in successful intervention rate. New possible options to Vancocins are hence needed. Daptomycin and linezolid are two new antibacterial agents discussed in this reappraisal. The pharmacokinetics, pharmacodynamic, side effects, opposition and indicants are mentioned in this reappraisal and comparings between Vancocin and linezolid are made. Treatment option is based on patient ‘s acceptableness, opposition, side-effects, path of disposal, site of infection and cost.
Staphylococcus aureus is a Gram-positive bacteria that colonises the tegument and is present in the anterior nares in about 25-30 % of healthy people. S. aureus can do different diseases in adult male depending on its intrinsic virulency or the ability of the host with its timeserving behaviour. [ 1 ] Resistance of antibiotics of the bacteriums can be acquired by the mutant of an bing bacterial cistron or horizontal transportation of a immune cistron from another bacterial cell. Among the opposition strain that have been isolated, meticillin opposition is clinically the most of import because S.aureus with this cistron resist the most normally prescribed category of antibiotics which is the beta-lactam antibiotics, including penicillins, Mefoxins and carbapenems. It is named meticillin-resistance staphylococci aureus ( MRSA ) . It can infect human from outside to inside, from tegument, ear, nose, generative piece of land, blood, bone, articulation, and the cardinal nervous system. It peculiarly affects kids, aged and people who are immunocompromised such as HIV and patients on immunosupressive drug after organ graft. [ 2 ]
MRSA was foremost discovered in the UK in 1961, half a twelvemonth after the debut of meticillin into the community and became one of the most prevailing bacteriua globally that cause an infection, runing from 2 % in the Netherlands and Switzerland, to 70 % in Japan and Hong Kong. [ 2, 3 ] The prevalence rate in the UK was 1.28 % in the twelvemonth 2006, with skin and soft-tissue infection ( 49.1 % ) which is the commonest infection type among all MRSA infections followed by eyes, ENT and mouth infections ( 29.3 % ) , bone and joint infections ( 28.1 % ) and surgical site infections ( 27.6 % ) . Others include urinary piece of land infections, bacteraemia, endocarditis and respiratory piece of land infections. [ 4 ]
Vancomycin has been used long and still is the standard intervention for MRSA infections. However, due to its weak disinfectant consequence, hapless incursion into tissues, particularly in the lung, toxicity and turning of opposition, find of new curative agents that are active against MRSA is of import. Linezold and daptomycin are newer antibacterial agents developed and are used as options to vancomycin. Linezolid can be administrated orally so before exchange to unwritten dosing is enabled. On the other manus, daptomycin has no CYP450 related-drug interaction so it is safer when used in patients on multi-drug therapies. They can be considered as the first-line intervention pick and used if vancomycin intervention is failed or contraindicated, for illustration patients with old hearing loss. Nevertheless, they have similar clinical results when compared with Vancocin with certain conditions. They are besides more expensive and toxicity profile is non improved but merely different. The pharmacokinetic belongingss, pharmacodynamic belongingss, side effects, opposition, efficaciousness and cost are discussed in this reappraisal and comparing is made between linezolid and Vancocin. [ 5-10 ]
Vancomycin belongs to an antibiotic category called glycopeptid produced by Amycolatopsis orientalis, a species in the actinobacteria category by agitation and it was isolated in the twelvemonth 1953. [ 10 ] From the past 50 old ages until presents, Vancocin is still the standard intervention for MRSA infections. [ 5 ]
It is a big hydrophilic molecule which does non traverse through the gastro-intestinal liner. Its unwritten usage is merely indicated for Clostridium difficile infection which unwritten disposal is necessary for the drug to make the colon.
As Vancocin is non orally absorbed, it is administered intravenously for the intervention of MRSA infection. However, Vancocin is non suited for IV bolus injection and rapid extract. It is really annoying to personify tissue and it can do injection site mortification, terrible hurting and thrombophlebitis if it is administered by IV injection. Rapid IV extract may do occasional hypotenion, histamine like response and erythematous roseola, besides known as ‘red adult male syndrome ‘ which may last for 20 proceedingss to several hours. Slow intermittent extract is more preferred than uninterrupted extract which should merely be used if intermittent extract is non suited. Rate of extract of Vancocin is suggested at a maximal rate of 10mg/min over 1 hr to avoid these anaphylactic reactions and trough serum concentration can be maintained above the MIC. [ 11 ] Longer extract clip is required for a stronger doses and slow extract over at least an hr is recommended for baby and kids. Furthermore, the hazard of o.d.ing and developing toxicity consequence from high extremum concentration is reduced. [ 10, 11 ]
Vancomycin undergoes no metamorphosis and is excreted unchanged in the piss. Clearance of Vancocin from the organic structure is extremely dependent on the nephritic map of the patient. Increased blood concentration can be a consequence of reduced nephritic map and may take to toxicity, include farther nephritic harm and ototoxicity. Therefore, alteration of the dosing government is indispensable, based on the creatinine clearance of each person and the optimal doses and dosing intervals can be deduced. [ 12 ] .
Nephrotoxicity is one of the important side effects followed by high dosage, prolonged or combined vancomycin therapy with aminoglycoside. Serum creatinine degree of all patients having Vancocin should be closely monitored, particularly if the patient is renally impaired. Aminoglycoside itself is a nephrotoxic drug. Hazard of nephritic harm is increased notably when Vancocin and aminoglycoside are used in combined therapy. [ 7, 10, 13 ] Several surveies has been carried out to look into the hazard of nephritic harm consequence from Vancocin monotherapy, aminoglycoside monotherapy and combined therapy of both drugs.
Seven surveies have been meta-analyzed and the hazard of nephrotoxicity with combination therapy was 13.3+ 3.1 % ( 7.3 – 19.4 % ) greater than therapy with Vancocin entirely ( P & lt ; 0.01 ) , and 4.3+ 1.4 % ( 1.6 – 7.0 % ) greater than aminoglycoside alone ( P & lt ; 0.05 ) . The consequences indicated that other than combined therapy of Vancocin and an aminoglycoside which is one of the chief factor of increased hazard of nephrotoxicity, prolonged intervention with Vancocin ( & gt ; 21days ) and vancomycin trough serum concentration ( & gt ; 10mg/L ) could besides be a cardinal factor taking to nephritic harm. Therefore, vancomycin entirely or in combination with an aminoglycosides should be used with cautiousness and close proctor on the nephritic map is indispensable. [ 14 ] Long term vancomycin/aminoglycoside combine therapy is besides discouraged.
Ototoxicity is another side consequence resulted from vancomycin therapy and is dose related. Although it is less likely to happen than nephritic harm, it is still important. Unlike nephritic toxicity, consequence obtained from survey look intoing audile harm is more dependable as it is improbable to be caused by other clinical factors that occur in the infirmary environment. A survey investigated 89 patients who had audiogram before and after 27days of Vancocin therapy. 11/89 patients ( 12 % ) consequence in declining in audiogram after the class, with 0/89 ( 0 % ) patients aged below 53 old ages and 11/89 patients ( 12 % ) aged 53 or supra. These informations suggested that middle-aged and aged patients are under a greater hazard of developing ototoxicity if they are treated with high-dose, long-run Vancocin therapy. Use of Vancocin should therefore be avoided, if possible for middle-aged, aged and patients with old hearing loss.
[ 10, 15 ]
Vancomycin is an antibiotic that exhibits assorted different pharmcokinetics of bacterial violent death and the most recognized theoretical account is MIC/AUC. MIC value should be & lt ; 1mg/L when it is used as monotherapy against to the full susceptible S. aureus ( VSSA ) . Its manner of action is to organize H bond with the D-Ala-D-Ala group on the bacterial cell wall and it prevents the junction of the NAM/NAG-peptide fractional monetary units into the peptidoglycan matrix. The cell wall synthesis procedure is instantly inhibited and the cytoplasmatic membrane is damaged as a secondary consequence. [ 10 ]
The cardinal indicant of Vancocin is for MRSA bacteraemia, serious soft tissue infection ( SSTI ) and bone infection.
Bacteraemia – It is suggested the intervention continuance of glycopeptides for unsophisticated bacteraemia should be at a minimal length of 14 yearss. Patients with, or at high hazard of endocarditis should have longer intervention.
SSTI – For non hospitalized patients, Vancocin should be used when the strains of MRSA are immune to doxycycline or clindamycin.
– For hospitalized patients, usage of Vancocin should be considered for terrible SSTI and if the hazard of bacteraemia is high.
Bone infection – Choice of antibiotics depends on the surgical direction program. As the information from clinical tests on the efficaciousness of the new agents are non sufficient to back up their usage, parenteral glycopeptides with or without adjunctive agents remains the lone recommendation.
[ 7 ]
2.4 VSSA, h-VISA, VISA and VRSA
The first designation of vancomycin-resistant S. aureus ( VRSA, MIC & gt ; 16mg/L ) was in the United States in 2002, due to the acquisition of the vanA cistron from vancomycin-resistant enterococci. However, merely 11 instances have been reported so far, with nine from the US, and the staying from India and Iran, which represents this strain is non widely spread. This reappraisal will non concentrate on this strain as it did non do a big figure of clinical issues. [ 16 ]
Heterogeneous vancomycin-intermediate S. aureus/Vancomycin-intermediate S. aureus ( hVISA/VISA, MICs 4-8mg/L ) were foremost isolated in Japan in 1996, from a spectrum of a patient with MRSA pneumonia who failed in standard Vancocin therapy. It has been found in many states including US, Hong Kong, Thailand, Japan and the UK, with at least one survey demoing 86 out of 2550 patients in Liverpool have been colonized with VISA [ 17 ] . Although the opposition mechanism of VISA is non certain, VISA cell wall is shown to be thicker than to the full susceptible S. aureus. Thickening of the cell wall protects the VISA from vacomycin, by forestalling the suppression of the peptidoglycan biogenesis procedure and let production of new cell wall peptidoglycan, which the cell is hence vancomycin resistant. [ 18 ]
A term ‘vancomycin weirdo ‘ has been mentioned in recent old ages. It is associated with diminishing activity of Vancocin for MRSA infection. Certain isolates of MRSA remains susceptible to vancomycin but the MICs are raised. [ 5 ]
The ground why increased MICs of vancomysin for MRSA infection is a concern is that the hazard of toxicity is raised and new, more expensive antimicrobic agents with deficient clinical and efficaciousness informations support have to be use as an option.
Therefore, to forestall spreading and halt the development of new strains, usage of Vancocin should be controlled and in some state of affairs is discouraged, including everyday surgical prophylaxis unless the patient is badly sick and empiric antimicrobic therapy for a feverish neutropenic patient unless initial groundss support that the infection is caused by Gram-positive being. The Healthcare Infection Control Practices Advisory Committee ( HICPAC ) besides suggests educating the hospital staff about Vancocin opposition, early sensing and coverage of Vancocin opposition by the infirmary microbiology research lab and using immediate infection control process to forestall transmittal of the bacteriums. [ 7, 19 ]
Daptomycin is a cyclic lipopeptide natural merchandise that is merely active against Gram positive bacteriums. It shows rapid concentration-dependent bactericidal activity. [ 20 ] Its manner of action is the calcium-dependent interpolation of its lipotropic tail on the cytoplasmatic membrane of the bacterial cell, doing a net outflow of K and hence DNA, RNA and protein synthesis is inhibited. It does non perforate the cytoplasmatic membrane so no cell lysis occurs. Less allergic responses is the consequence as there is no release of molecules from the cytol which inflammatory response can be diminished. [ 5, 6, 9 ] It exhibits concentration-dependent bactericidal activity in pharmacodynamic surveies and in vitro. The continuance of post-antibiotic consequence of daptomycin is more than 6h at 16mg/L which is much longer and effectual as compared with 1.3-1.8h time-dependent post-antibiotic consequence of Vancocin.
[ 6 ]
Daptomycin is a extremely protein bounded drug ( 92 % ) with a half life of about 8h, which allows it to be administered one time day-to-day. [ 5 ] Single daily dose of 4-10mg/kg administered by endovenous extract should be over 30 proceedingss for up to 14 yearss in persons with normal nephritic map and steady-state concentration should be reached by the 3rd day-to-day dosage. CYP450 mediated metamorphosis has no or small consequence on metabolising daptomycin and hence no CYP450-related drug interaction is expected. It is chiefly excreted by the kidney and therefore it should be used with cautiousness and with regular nephritic map monitoring in nephritic impaired patients ( Creatinine clearance & lt ; 80ml/min ) . [ 9 ] Patients who are hepatic failed do non necessitate dose accommodations, but is necessary in nephritic impaired patients and a complementary dosage after hemodialysis is required as the 4-h dialysis subdivision clears 15 % of the drug. [ 5 ] Co-administration of medicine that reduces nephritic filtration, such as NSAIDs and COX-2 inhibitors may take to an addition in daptomycin plasma degree as the clearance rate is lowered. Therefore, co-administration of daptomycin with any other medicine that reduces nephritic map should be used with cautiousness. [ 9 ]
Side effects such as diarrhoea, roseola, fungous infection are still common following antibiotic therapy, but one unique to daptomycin is skeletal musculus toxicity. Symptoms include musculus hurting and reduced musculus strength. It is reversible if daptomycin is discontinued every bit shortly as symptoms are observed. [ 5,9 ] It is found that the dosing frequence is the major factor doing toxicity. A spliting dosage of daptomycin every 8h gives a greater addition in CPK and more terrible debasement of myofibres than a big individual day-to-day dosage. Co-therapy of daptomycin and lipid-lowering medicines is besides thought to be a factor doing myopathy. Therefore, recommendations are made to hold close monitoring of CPK and muscular map in all patients started on daptomycin and avoid co-administration with lipid-lowering medicines or other medicine casuing myopathy. [ 21 ]
Resistance of daptomycin is uncommon but it can develop as a consequence of drawn-out intervention. Several mutants of the S. aureus cistrons are responsible for the decrease of susceptibleness. The mprF cistron encodes a affaire d’honneur map enzyme that binds phosphatidylglyerol ( PG ) to lysine and lysyl-PG ( LPG ) is so transferred to the surface of the outer membrane. LPG is less susceptible to daptomycin than PG as it is less acidic. The calcium-dependent interpolation of the lipotropic tail is unfavourable and binding of daptomycin is reduced. Ration of LPG/PG in the outer membrane of the bacteriums with mprF mutations is higher than the wide-type strain and bind less daptomycin is the consequence. [ 22 ]
One concern is the decreased or non-susceptibility of MRSA to daptomycin after failure in Vancocin therapy. Resistance or reduced susceptibleness to vancomycin due to antibiotic force per unit area exerted by daptomycin, or frailty versa and intervention failure is the consequence. [ 7 ] On the other manus, one survey evaluated daptomycin and Vancocin against two strains of VSSA and four strains of VISA with endocardial flora in a pharmacokinetic/pharmacodynamic theoretical account. Daptomycin showed disinfectant activity against both VRSA and VISA isolates while Vancocins displayed small activity against VSSA isolates and small to no activity against hVISA. This survey concluded by proposing daptomycin can be a possible agent for intervention of serious infection caused by hVISA and an alternate if vancomycin therapy failed. [ 23 ] The consequences from both surveies are beliing and as there is no clear and good accepted clinical test done, daptomycin is hence non yet licensed for GISA and glycopeptides-resistance S. aureus ( GRSA ) infection. [ 7 ]
Daptomycin is recommended by the BSAC Guideline for MRSA SSTI and bacteraemia including right-side endocarditis. [ 7, 24 ] One survey showed 45 % versus 27 % in complicated bacteraemia, 60 % versus 45 % in unsophisticated bacteraemia and 50 % versus 50 % in right-side endocarditis of the patients successfully treated with daptomycin and Vancocin plus Garamycin severally. The information indicate that daptomycin is an effectual option to vancomycin/gentamicin for bacteraemia or right-side endocarditis which MRSA is the causative being. [ 25 ] Furthermore, comparison with Vancocin or isoxazoyl penicillin with Garamycin which was associated with nephrotoxicity, daptomycin casued less toxicity and is reported in another test. Treatment failure of left-side endocarditis by daptomycin has besides been shown. [ 7 ]
Patients with MRSA SSTI on daptomycin therapy should have a day-to-day dosage of 4mg/kg and 6-10mg/kg for bacteraemia or endocarditis. Furthermore, bone and joint infection has been successfully treated with daptomycin but randomized comparative tests have non been published. [ 5 ]
Study has shown all strains that cause complicated UTI are susceptible to daptomycin with MICs up to 2mg/L. Rate of bacteriological obliteration is 83 % and clinical success rate is 93 % . However, BSAC indicates that 2mg/L should be classified as immune.Therefore daptomycin is still non a accredited drug to handle UTI caused by MRSA but it is used through empirical observation. [ 7 ]
Furthermore, the usage of daptomycin for MRSA pneumonia is discouraged. It is because daptopmycin is inactivated by adhering of its lipotropic portion to the pneumonic wetting agent found in the lung. Its antimicrobic activity is hence inhibited. [ 26 ]
Linezolid belongs to a new category of antibiotic category called oxazolidinones and it is the lone member of this category marketed by the twelvemonth 2009. It demonstrates in vivo and in vitro bacteriostatic activity against aerophilic Gram positive bacteriums and anaerobiotic microorganisms, including MRSA and VISA. It binds to the 23S and 50S fractional monetary unit on the bacterial ribosome and the formation of a functional 70S induction composite is prevented. Bacterial protein synthesis is selectively inhibited as 70S is an indispensable constituent of the interlingual rendition procedure. [ 6, 8 ]
Due to it alone mechanism of action, cross-resistance of linezolid with other antibacterial agents ( such as Chloromycetin, quinupristin-dalfopristinhas and Achromycin ) has non been reported. [ 27 ] However, mutant on the 23S rRNA cistron is the chief cause of resistant of MRSA as the binding of linezolid to this 23S rRNA fractional monetary unit is obstructed, which leds to an addition in the MICs. [ 28 ]
Linezolid can be administered by IV extract or by unwritten path. Both dose signifiers are bioequivalent. Oral soaking up of the drug is rapid and complete, with bioavailability at approximately 100 % that allows early switch to unwritten therapy every bit shortly as the patients are clinically stable. It can cut down Vancocin usage and the length of stay ( LOS ) in hospital lead to a decrease of the cost. [ 5, 6, 8, 29, 30 ] It reaches the peak plasma concentration after 2 hours of unwritten disposal and it is quickly disturbed into organic structure tissue. [ 8, 29 ] . It is metabolized into two inactive metabolites by oxidization of the morpholine ring and non-renal clearance histories for 65 % of the entire clearance of linezolid. 30 % of the active drug is excreted in the piss and the last 5 % is removed in the fecal matters. Linezolid is non metabolized by CYP450 and hence no CYP450 -drug related interaction is expected. [ 8 ]
Linezolid is by and large good tolerated, with about 22 % of patients experient non-life endangering inauspicious reactions. Those most normally reported side effects are concern, diarrhea, sickness, purging, metallic gustatory sensation, unnatural liver map trials and vaginal and unwritten moniliasis. Most of the patients discontinued the intervention because of concern, diarrhea, sickness and emesis, with a rate of 3 % of 2000 grownup patients who received the recommended linezolid dosage for up to 28days. [ 8, 29 ]
Linezolid itself is besides a weak, reversible, non-selective monoamine oxidase inhibitor ( MAOI ) . Curative dose used for antibacterial therapy is excessively low and no anti-depressive consequence is shown. Drug-drug interaction is evaluated by limited surveies and its usage on patients with implicit in conditions or on co-administration of mediation might set them at hazard from MAOI suppression. Close monitoring is necessary if usage of linezolid is the lone curative option in these conditions. Furthermore, big sum of tyramine consumption should besides be restricted to avoid ‘cheese syndrome ‘ . Food with rich tyramine content includes mature cheese, pickled meat, fish and yoghurt. [ 8, 29 ]
Serotonin syndromes have been reported with the accompaniment usage of linezolid and serotonergic agent such as serotonin re-uptake inhibitors ( SSRIs ) . Therefore, unless the co-administration of linezolid and serotonergic agents is critical, either of them should be avoided. Close observation and monitoring for the marks and symptoms of serotonin syndrome inducement hyperpyrexia, cognitive disfunction, hyperreflexia and incoordination is indispensable. Discontinuing of either one or both agents should be considered detecting that discontinuance symptoms may develop followed by the backdown of the serotonergic agent. [ 8 ]
Myelotoxicity and neurotoxicity are the major terrible side effects as a consequence of linezolid therapy.
Mytoxicity has been reported when the continuance of intervention exceeded 10 yearss and particularly happening in patients with preexistent myelosuppresion or having another myelotoxic drug. Complications include anemia, leucopenia, pancytopenia, and thrombopenia are observed. Renally impaired patients see a bead in thrombocyte count more normally. These patients should hold close monitoring on their thrombocyte counts and hemoglobin degrees. Recommendation is besides made to supervise complete blood counts hebdomadal for patients who are having linezolid intervention transcending 14 yearss, having co-current drugs that are besides myelotoxic, with preexistent myelosuppreion, or those with a chronic infection who have received old or attendant antibiotic therapy. [ 29 ]
Neurotoxicity may be induced by drawn-out usage of linezolid. Symptoms include both peripheral and ocular neuropathy, which can be exacerbated by several hazard factors such as preexistent neurologic job, intoxicant maltreatment, diabetes and accompaniment of a serotonin re-uptake inhibitor or antihistamine. Close neurological monitoring is hence recommended in drawn-out linezolid therapy and with attendant hazard factors. [ 31, 32 ] A maximal continuance of 28 yearss intervention class has besides been suggested by the makers and clinical surveies. [ 5 ]
Serious soft-tissue infection is one of the accredited indicants of linezolid, particularly complicated SSTI and. In a randomised, open-label, comparator-controlled, multicenter and transnational survey, affecting 1180 patients, unwritten linezolid was compared with i.v. Vancocin in patients with cSSTI infection that involves significant country of tegument or deeper soft tissues such as cellulitis, abscesses, septic ulcers or Burnss. Clinical successful rate was 92.2 % and 88.5 % for the linezolid group and Vancocin severally which was tantamount. Similar figure of instances of drug-related side effects has besides been reported, with a more common rate of 3.5 % of patients developed thrombopenia in the linezolid group. However, 88.6 % of the linezolid group showed better result than the Vancocin group at the test-of-cure ( TOC ) visit which suggested linezolid is a better pick when handling cSSTI caused by MRSA. [ 33 ] Another survey which was a meta-analysis of randomized controlled tests besides indicated that patients treated with linezolid ( 89 % ) have a somewhat higher successful rate of remedy than Vancocin ( 86 % ) . [ 34 ]
Another status when linezolid is frequently chosen as an option of intervention is pneumonia, particularly ventilator-associated pneumonia ( VAP ) . Clinical successful rate between linezolid and Vancocin showed no important different. However, the length of ICU stay and hospitalization of the linezolid group ( 12.2d, 18.8d severally ) is shorter than that of the Vancocin group ( 16.2d, 20.1d severally ) , which enable an earlier discharge, reduces exposure clip to nosocomial pathogens and allows efficient usage of resources for patients treated with linezolid.
[ 35 ]
Linezolid is ever being used to handle bone and joint infections and cardinal nervous system infections, including meningitis and encephalon abscesses. Although it is non licensed for the intervention of both conditions because of the hazard of inauspicious effects development, it is still used through empirical observation. [ 5, 7 ]
Linezolid is besides suggested for handling PVL-positive MRSA infections. Panton-Valentine leucocidin ( PVL ) is a white blood cell destructing toxin and a staphylococci virulency factor produced by some strains of S. aureus/MRSA and more normally CA-MRSA. Severe SSTIs and terrible necrotizing pneumonia can be caused by this toxin and may necessitate more advanced diagnosing and intervention program. Linezolid is used in these instances in combination with Vancocin or other antibacterial agents such as clindamycin, rifampicin and co-trimoxazole because of its ability to suppress the production of PVL from the PVL-positive MRSA strains. Clinical successful rate is besides higher when patients are treated with linezolid-combined therapy than that of other antibiotics. [ 7,37 ]
Other than the efficaciousness of the antibacterial agent which is doubtless the chief factor on taking intervention option, the cost of the drug is besides of import. Therefore, surveies are carried out to look into the cost-effectiveness of linezolid versus Vancocin. Sing to the shorter length of stay ( LOS ) and earlier discharge from infirmary, the mean cost per patient treated with unwritten linezolid is 28.5 % and 22.3 % less than the i.v. Vancocin group and the group treted with i.v. Vancocin followed by unwritten linezolid, severally. Although a individual dosage of linezolid is more expensive than an equality dosage of vancomcyin, the difference in the monetary value of the drug is overcame by the salvaging on the decreased hospitalization period. Linezolid is hence a more cost-efficient antibacterial agent for MRSA infection than Vancocin. [ 36 ]
Vancomycin, daptomycin and linezolid are three antibiotics from different antibacterial household that are licensed for MRSA infections. They are non the lone three picks but they are the three most of import and most widely used antibiotics for MRSA infections. Clinicians have to judge and determination is based on patient ‘s acceptableness, opposition, side-effects, path of disposal, site of infection and cost.
Choosing the proper antibiotics for different infections is important. Harmonizing to the “ Guidelines ( 2008 ) for the prophylaxis and intervention of methicillin-resistant Staphylococcus aureus ( MRSA ) infections in the United Kingdom ” , all three of them are licensed for bacteraemia and SSTI but there are small differences between them.
Linezolid has shown to hold better clinical result than Vancocin for the intervention of MRSA SSTIs and bacteraemia. [ guideline ] It can be considered as a replacing of Vancocin for the pick of first line intervention. [ 7, 39 ] As linezolid is merely more cost-efficient than Vancocin in patients necessitating hospitalization ( such as pneumonia and bacteraemia ) , vancomycin and daptomycin are still more cost-efficient than linezolid for outpatient therapy in reasonably terrible SSTIs ; Daptomycin is unlicensed for UTI but is used through empirical observation. Further clinical tests are in advancement to hold daptomycin proven for its utilizations in more conditions ( except pneumonia which is already proven as uneffective ) . [ 38 ]
Patients with multiple medical conditions and on multi-drugs therapy can besides perplex the state of affairs. Use of drugs on this group of patients should be with cautiousnesss and with close monitoring. Combine therapy of Vancocin with an aminoglycoside has a higher nephrotoxicity incident rate than mono-vancomycin therapy and may hold further deterioration of nephritic map for patients with preexisting nephritic job. Linezolid can be an alternate in this instance. It can besides be used, alternatively of Vancocin for patients who are middle-aged or aged with old hearing loss to avoid farther harm to the hearing ability. Notice that co-administration of linezolid and a serotonergic agent such as SSRIs should be avoided.
In drumhead, we have looked at the pharmacokinetics, pharmacodynamic, opposition, indicant and side effects of these three antibiotics. We have besides compared the efficaciousness of vancomycin/linezolid. Daptomycin is non compared in this reappraisal because of deficient informations published. Limited clinical surveies have done on daptomycin versus Vancocin for MRSA infections.