Why is methicillin different from penicillin

More clinical studies of clinical efficacy are needed, especially with comparative trials. Selection of the most appropriate antibiotic will depend upon local antibiotic resistance, type of infection, potential adverse effects, and cost for the individual. Abstract Background: The emergence of methicillin-resistant Staphylococcus aureus MRSA as a cause of hospital- and community-associated infection has been reported worldwide and has become an increasing health care problem.

Publication types Review. Nucleic acid amplification tests, such as the polymerase chain reaction PCR , can be used for direct detection of mecA , the most common gene mediating oxacillin resistance in staphylococci. However, mecA PCR tests will not detect novel resistance mechanisms such as mecC or uncommon phenotypes such as borderline-resistant oxacillin resistance.

An alternative method for detection of MRSA is the use of anti-PBP2a monoclonal antibodies available as latex agglutination or immunochromatographic membrane assays. Finally, there are commercially available chromogenic agars that can be used for MRSA detection. Cefoxitin should be used as a surrogate for disk diffusion testing. First, methicillin is no longer commercially available in the United States. Second, oxacillin maintains its activity during storage better than methicillin and is more likely to detect heteroresistant strains.

However, cefoxitin is an even better inducer of the mecA gene, and tests using cefoxitin give more reproducible and accurate results than tests with oxacillin. When resistance was first described in , methicillin was used to test and treat infections caused by S. However, oxacillin, which is in the same class of drugs as methicillin, was chosen as the agent of choice for testing staphylococci in the early s, and this was modified to include cefoxitin later.

The acronym MRSA is still used by many to describe these isolates because of its historic role. Section Navigation. Facebook Twitter LinkedIn Syndicate.

Laboratory Testing Minus Related Pages. On this Page. Can all susceptibility tests detect MRSA? External factors that affect methicillin resistance include among others, salt concentration, pH, medium composition, osmolarity and temperature Why NaCl concentration and temperature have this affect is not known.

A few compounds are known to affect the expression of the mecA gene. For compounds such as the polyoxotungstates 31 and totarol 32 , the synthesis of PBP2a is reduced but the mechanism of how this is achieved is not known.

For others, such as polidocanol a dodecyl polyethyleneoxide ether 33 , and glycerol monolaurate 34 the site of action is thought to be the cytoplasmic membrane where they interfere with either the signalling domain of MecR1 or some other protein involved in signal transduction.

The non-ionic detergent Triton X is also thought to target the cytoplasmic membrane but it does not interfere with PBP2a production. Strains grown in the presence of Triton X have increased susceptibility to methicillin and have increased rates of bacteriolysis MRSA grown in the presence of triton X are converted from a homogeneous to a heterogeneous phenotype, although there appears to be strain-to-strain variability.

Inactivation or partial disruption of the fmt genes, fmtA and fmtB , have been shown to enhance triton Xmediated methicillin sensitivity. Inactivation of the fmtA gene affects the cell wall structure but the precise role of the FmtA protein has not been determined. How the inactivation of the fmtB gene results in a reduction in methicillin resistance is also not known, but methicillin resistance can be restored by the addition of cell wall precursors, glycosaminephosphate and N-acetylglycosaminephosphate Other compounds are known not to affect PBP2a synthesis and interfere with the activity of PBP2a, these include licoricidin, a phenolic compound isolated from commercial licorice 38 , and the triazine dye, cibacron blue F3GA Epicatechin gallate ECG and epigallocatechin gallate EGCG Figure 4 are polyphenolic compounds present in green tea Camellia sinensis that have activities against a wide range of bacteria At high concentrations epicatechin gallate selectively inhibits the growth of methicillin-resistant S.

Under the electron microscope cells treated with green tea extracts have gross morphological changes characterised by the clumping together of partial divided cells that have thickened internal cell walls Methicillin-sensitive strains appear to be unaffected by the extract. The action of ECG in combination with oxacillin is bactericidal EGCG does not appear to affect transcription of the mecA gene and has been proposed to exerts its effect through direct binding to peptidoglycan The chemical structures of the polyphenolic compounds, epicatechin gallate and epigallocatechin gallate present in green tea Camellia sinensis.

Green tea administered as a spray has been successfully used in the treatment of an MRSA infection of the trachea windpipe Unfortunately, epicatechin gallate cannot by widely administered because it is broken down by esterases in the body to the inactive products, epicatechin and gallic acid.

This prevents the oral or parenteral co-administration of ECG with oxacillin or methicillin. Recently, two other polyphenolic compounds, corilagin 47 , extracted from the leaves of Arctostaphylos uva-ursi and tellimagrandin I 48 extracted from the petals of rose red Rosa canina L. Both compounds act synergistically with oxacillin.

Further investigations into the mechanisms of action of these polyphenolic compounds combined with the synthesis of more stable derivatives are warranted.

Peptidoglycan synthesis is a complex process involving the coordination of both biosynthetic and degradative pathways. PBP2a is not native to S. Unfortunately, PBP2a is less sensitive to the action of methicillin and is capable of conferring methicillin resistance. Fortunately, the substrate requirements of PBP2a are relatively strict and this is a weakness that can be exploited. By targeting and inhibiting the proteins, such as FemA and FemB, involved the formation of these substrates, methicillin resistance can be modulated.

Compounds such as epicatechin gallate and corilagin are attractive compounds to develop into therapeutic agents since these compounds exist already and are known to modulate methicillin resistance. Paul D. His research interests include the mechanisms of antibiotic resistance, antibiotic resistance gene capture and spread, and the development and mode of action of new antimicrobial agents. His major research interests are novel approaches to the treatment of infectious disease.

Current topics include studies of the mechanism of photosensitisation of Gram-negative bacteria by liposome-delivered phthalocyanines and the use of photosensitisers for the treatment of topical infections, the optimisation of expression of recombinant proteins of commercial medical interest, and novel approaches to the treatment of infections due to methicillin-resistant staphylococci, mycobacteria and other medically important bacteria.

National Center for Biotechnology Information , U. Sci Prog. Author manuscript; available in PMC Nov 7. PAUL D. Copyright and License information Disclaimer. Copyright notice.

The publisher's final edited version of this article is available at Sci Prog. See other articles in PMC that cite the published article.

Abstract Staphylococcus aureus is a major pathogen both within hospitals and in the community. Open in a separate window. Internal factors affecting methicillin resistance Since PBP2a is essential in conferring methicillin resistance, any factor that interferes with the expression of the mecA gene or with the activity of PBP2a will affect methicillin resistance. Studies have shown that PBP2a requires: Glycan chains to be of certain lengths.

External factors that affect methicillin resistance External factors that affect methicillin resistance include among others, salt concentration, pH, medium composition, osmolarity and temperature Concluding remarks Peptidoglycan synthesis is a complex process involving the coordination of both biosynthetic and degradative pathways.

Acknowledgement The authors are grateful to the Medical Research Council for financial support. References 1. Chambers HF. Methicillin resistance in staphylococci: molecular and biochemical basis and clinical implications. Livermore DM. Antibiotic resistance in staphylococci.

Staphylococcal cell wall: Morphogenesis and fatal variations in the presence of penicillin. Role of Fem factors in methicillin resistance. Drug Resisance Updates. Borderline susceptibility to methicillin in Staphylococcus aureus : a new mechanism of resistance?