Vancomycin susceptibility

S. A. Roberts, J. Robson, K. Read, N. Bak, J. Hurley, P.D.R. Johnson, A.J. Morris, B.C. Mayall, and M.L. Grayson (2004). Treatment outcomes for serious infections caused by methicillin-resistant Staphylococcus aureus with reduced vancomycin susceptibility. Clinical Infectious Diseases 38 521-528. 

Howe R.A., A. Monk, M. Wootton, T.R. Walsh, and M.C. Enright (2004). Vancomycin susceptibility within methicillin-resistant Staphylococcus aureus lineages. Emerging Infectious Diseases 10 855-857. 

Hiramatsu et al Methicillin resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility. J Antimicrob Chemother 1997 40 135. [PMID 9249217]... 

Resistance to vancomycin in enterococci is due to modification of the D-Ala-D-Ala binding site of the peptidoglycan building block in which the terminal D-Ala is replaced by D-lactate. This results in the loss of a critical hydrogen bond that facilitates high-affinity binding of vancomycin to its target and loss of activity. This mechanism is also present in vancomycin-resistant S aureus strains (MIC s32. ug/mL), which have acquired the enterococcal resistance determinants. The mechanism for reduced vancomycin susceptibility of vancomycin-intermediate strains (MICs = 8-16 g/mL) is not known. 

NE Allen, JN Hobbs Jr, TI Nicas. Inhibition of peptidoglycan biosynthesis in vancomycin-susceptible and -resistant bacteria by a semisynthetic glycopeptide antibiotic. Antimicrob Agents Chemother 40 2356-2362, 1996. 

Vancomycin/glycopeptide intermediately resistant and methicillin-resistant S. aureus have been described in Japan, Europe, the Far East, and the USA. Some vancomycin-susceptible strains of S. aureus contain subpopulations with intermediate resistance to vancomycin (heterogeneous strains), and these may escape laboratory detection (93,94,97-99). 

All enterococci causing endocarditis must be tested for antimicrobial susceptibility in order to select optimal therapy (see text). This table is for endocarditis due to gentamicin- or vancomycin-susceptible enterococci, viridans streptococci with a minimum inhibitory concentration of >0.5 mcg/mL, nutritionally variant viridans streptococci, or prosthetic valve endocarditis caused by viridans streptococci or Streptococcus bovis. Antibiotic dosages are for patients with normal renal function. 

Daptomycin is indicated in treatment of complicated skin and skin-structure infections caused by methicillin-susceptible and methicillin-resistant strains of S. aureus, hemolytic stteptococci, and vancomycin-susceptible E. faecalis. Its efficacy is comparable to that of vancomycin. Efficacy in more serious infections, such as endocarditis or complicated bacteremia, has not been demonsttated, although clinical ttials are under way. Daptomycin was inferior to comparators for treatment of community-acquired pneumonia and is not indicated for this infection. 

Figure 7 Localization of cell wall synthesis in isogenic pairs of vancomycin-susceptible and vancomycin-resistant Staphylococcus aureus strains. Images show labeling of JH1/JH9 (susceptible) and COL/VM50 (resistant) cells with a fluorescent vancomycin derivative, after growth with an excess of o-serine (synthesis of older peptidoglycan with D-Ala-D-ser termini, to which the labeled vancomycin cannot bind) followed by transient incubation with o-Alanine, which results in n-Ala incorporation into new peptidoglycan, to which the vancomycin can bind. In all cases, the main location for cell wall synthesis is at the division septum. Data reproduced from P. M. Pereira S. R. Filipe A. Tomasz M. G. Pinho, Antimicrob. Agents Chemother. 2007, 51 (10), 3627, with permission from the American Society for Microbiology.

Daptomycin is indicated for treatment of complicated skin and skin-structure infections caused by methicillin-susceptible and methicillin-resistant strains ofS. aureus, hemolytic streptococci, and vancomycin-susceptible E. faecalis. Its efficacy is comparable to that of vancomycin. 

Other specific discovery assays have been used such as differential inhibition of a vancomycin resistant S. aureus strain and its susceptible parent, and an assay based on antagonism of the antibacterial activity by N,A/-diacetyl-L-Lys-D-Ala-D-Ala [24570-39-6] a tripeptide analogue of the dalbaheptides receptor. AppHcation of this latter test to 1936 cultures (90) led to the isolation of 42 dalbaheptides, six of which, including kibdelin (Table 3), parvodicin (Table 3), and actinoidin A2 (68) were novel. A colorimetric assay based on competition between horseradish peroxidase bound teicoplanin and the... 

Vancomycin (Vancocin) acts against susceptible gram-positive bacteria by inhibiting bacterial cell wall synthesis and increasing cell wall permeability. This drug is used in the treatment of serious gram-positive infections that do not respond to treatment with other anti-infectives. It also may be used in treating anti-infective-associated pseudomembranous colitis caused by Clostridium difficile. 

Vancomycin is bactericidal to most susceptible bacteria at concentrations near its minimum inhibitory concentration (MIC) and is an inhibitor of bacterial cell wall peptidoglycan synthesis, although at a site different from that of j3-lactam antibiotics (Chapter 9). 

Traditionally, high-dose penicillin G was the treatment standard for meningococcal disease. However, increasing penicillin resistance requires that third-generation cephalosporins now be used for empirical treatment until in vitro susceptibilities are known.23 Patients with a history of type I penicillin allergy or cephalosporin allergy may be treated with vancomycin. Treatment should be continued for 7 days, after which no further treatment is necessary. 

CA-MRSA is susceptible to more antibiotics than HA-MRSA. Like HA-MRSA, CA-MRSA typically is sensitive to vancomycin, linezolid, daptomycin, tigecycline, and quinupristin/ dalfopristin, but it also may be sensitive to clindamycin, doxy-cycline, minocycline, and/or trimethoprim-sulfamethoxazole (TMP-SMX).14... 

Patients with PVE caused by penicillin-susceptible strains of viridans streptococci require treatment for 6 weeks with penicillin G or ceftriaxone with or without gentamicin during the initial 2 weeks of therapy. However, if the organism demonstrates less susceptibility to penicillin (MIC greater than 0.12 mcg/mL), a combination therapy with penicillin G or ceftriaxone plus gentamicin should be given for the entire 6 weeks. Vancomycin remains the primary alternative if the patient is allergic to (l-lactams (e.g., penicillins, cephalosporins, etc.). 

It is important to determine (1) whether the isolate is methicillin-susceptible or methicillin-resistant and (2) whether the patient has a prosthetic valve. For patients with no prosthetic material, methicillin-susceptible staphylococci treatment should consist of a penicillinase-resistant penicillin (e.g., nafcillin or oxacillin) with or without gentamicin, and for methicillin-resistant strains, therapy should consist of vancomycin (see Table 71-4). Combination therapy with aminoglycosides, when used in these patients, typically is given only during the first 3 to 5 days of therapy. In the absence of prosthetic material, some treatment guidelines do not recommend combination therapy against MRSA. However, many clinicians may combine either gentamicin or rifampin with vancomycin if the patient is unresponsive to monotherapy. 

For enterococci, it is imperative to determine species and antibiotic susceptibilities. If the organism is susceptible to penicillin and vancomycin, treatment may consist of high-dose penicillin G, ampicillin, or vancomycin plus gentamicin (see Table 71-6). Treatment length is usually 4 to 6 weeks, with the aminoglycoside used over the entire course. As resistance develops to penicillin, ampicillin and vancomycin remain treatment options. Once the isolate becomes resistant to ampicillin, vancomycin is considered the treatment of choice. 

For penicillin-allergic (nonanaphylactoid type) patients cefazolin 6 g/24 hours IV in 3 equally divided doses 6 IB Consider skin testing for oxacillin-susceptible staphylococci and questionable history of immediate-type hypersensitivity to penicillin cephalosporins should be avoided in patients with anaphylactoid-type hypersensitivity to P-lactams vancomycin should be used in these cases ... 

Penicillin C 24 million units/24 hours IV in 4 to 6 equally divided doses may be used in place of nafcillin or oxacillin if strain is penicillin-susceptible (minimum inhibitory concentration less than or equal to 0.1 mcg/mL) and does not produce P-lactamase. cGentamicin should be administered in close temporal proximity to vancomycin, nafcillin, or oxacillin dosing. 

Therapy for Native-Valve or Prosthetic-Valve Enterococcal Endocarditis Caused by Strains Susceptible to Penicillin, Gentamicin, and Vancomycin... 

Vancomycin may be added to the empirical regimen after 3 to 5 days in persistently febrile patients or if cultures reveal gram-positive organisms. Vancomycin should be changed if the gram-positive organism is susceptible to other antibacterials or discontinued in patients with persistent fever after 3 days with negative cultures. 

The answer is c. (Hardman, pp 1143-1144.) Bacitracin, cycloserine, cephalothin, and vancomycin inhibit cell-wall synthesis and produce bacteria that are susceptible to environmental conditions. Polymyxins disrupt the structural integrity of the cytoplasmic membranes by acting as cationic detergents. On contact with the drug, the permeability of the membrane changes. Polymyxin is often applied in a mixture with bacitracin and/or neomycin for synergistic effects. 

The treatment of choice until susceptibility of the organism is known as the combination of vancomycin plus ceftriaxone. Penicillin may be used for drug-susceptible isolates with minimum inhibitory concentrations of 0.06 mcg/mL or less, but for intermediate isolates ceftriaxone is used, and for highly drug-resistant isolates a combination of ceftriaxone and vancomycin should be used. A high percent of S. pneumoniae is either intermediately or highly resistant to penicillin. 

Vancomycin is the drug of choice for methiciUin-resistant staphylococci since most methiciUin-resistant S. aureus and most CNST are susceptible. 

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