For susceptible strains, the treatment of choice for S.<unk>  infection is penicillin. An antibiotic derived from some Penicillium fungal species, penicillin inhibits the formation of peptidoglycan cross-linkages that provide the rigidity and strength in a bacterial cell wall. The four-membered β-lactam ring of penicillin is bound to enzyme DD-transpeptidase, an enzyme that when functional, cross-links chains of peptidoglycan that form bacterial cell walls. The binding of β-lactam to DD-transpeptidase inhibits the enzyme's functionality and it can no longer catalyze the formation of the cross-links. As a result, cell wall formation and degradation are imbalanced, thus resulting in cell death. In most countries, however, penicillin resistance is extremely common (>90%), and first-line therapy is most commonly a penicillinase-resistant β-lactam antibiotic (for example, oxacillin or flucloxacillin, both of which have the<unk> me mechanism of action as penicillin) or vancomycin, depending on local resistance patterns. Combination therapy with gentamicin may be used to treat serious infections, such as endocarditis, but its use is controversial because of the high risk of damage to the kidneys. The duration of treatment depends on the site of infection and on severity. Adjunctive rifampicin has been historically used in the management of S<unk>  bacteraemia, but randomised controlled trial evidence has shown this to be of no overall benefit over standard antibiotic therapy. Antibiotic resistance in S.<unk>  was uncommon when penicillin was first introduced in 1943. Indeed, the original Petri dish on which Alexander Fleming of Imperial College London observed the antibacterial activity of the Penicillium fungus was growing a culture of S.<unk> . By 1950, 40% of hospital S.<unk>  isolates were penicillin-resistant; by 1960, this had risen to 80%. Methicillin-resistant<unk>  (MRSA, often pronounced or ), is one of a number of greatly feared strains of S.<unk>  which have become resistant to most β-lactam antibiotics. For this reason, vancomycin, a glycopeptide antibiotic, is commonly used to combat MRSA. Vancomycin inhibits the synthesis of peptidoglycan, but unlike β-lactam antibiotics, glycopeptide antibiotics target and bind to amino acids in the cell wall, preventing peptidoglycan cross-linkages from forming. MRSA strains are most often found associated with institutions such as hospitals, but are becoming increasingly prevalent in community-acquired infections. Minor skin infections can be treated with triple antibiotic ointment. One topical agent that is prescribed is Mupirocin, a protein synthesis inhibitor that is produced naturally by Pseudomonas fluorescens and has seen success for treatment of S.<unk>  nasal carriage. Antibiotic resistance mastitis in dairy cows: Its large capsule protects the organism from attack by the cow's immunological defenses. S.<unk>  was found to be the second leading pathogen for deaths associated with Antimicrobial resistance in 2019. Staphylococcal resistance to penicillin is mediated by penicillinase (a form of beta-lactamase) production: an enzyme that cleaves the β-lactam ring of the penicillin molecule, rendering the antibiotic ineffective. Penicillinase-resistant β-lactam antibiotics, such as methicillin, nafcillin, oxacillin, cloxacillin, dicloxacillin, and flucloxacillin are able to resist degradation by staphylococcal penicillinase. Susceptibility to commonly used antibiotics. Resistance to methicillin is mediated via the mec operon, part of the staphylococcal cassette chromosome mec (SCCmec). SCCmec is a family of mobile genetic elements, which is a major driving force of S.<unk>  evolution. Resistance is conferred by the mecA gene, which codes for an altered penicillin-binding protein (PBP2a or PBP2') that has a lower affinity for binding β-lactams (penicillins, cephalosporins, and carbapenems). This allows for resistance to all β-lactam antibiotics, and obviates their clinical use during MRSA infections. Studies have explained that this mobile genetic element has been acquired by different lineages in separate gene transfer events, indicating that there is not a common ancestor of differing MRSA strains. Interestingly, one study suggests that MRSA<unk> crifices virulence, for example, toxin production and invasiveness, for survival and creation of biofilms Aminoglycoside antibiotics, such as kanamycin, gentamicin, streptomycin, were once effective against staphylococcal infections until strains evolved mechanisms to inhibit the aminoglycosides' action, which occurs via protonated amine and/or hydroxyl interactions with the ribosomal RNA of the bacterial 30S ribosomal subunit. Three main mechanisms of aminoglycoside resistance mechanisms are currently and widely accepted: aminoglycoside modifying enzymes, ribosomal mutations, and active efflux of the drug out of the bacteria. Aminoglycoside-modifying enzymes inactivate the aminoglycoside by covalently attaching either a phosphate, nucleotide, or acetyl moiety to either the amine or the alcohol key functional group (or both groups) of the antibiotic. This changes the charge or sterically hinders the antibiotic, decreasing its ribosomal binding affinity. In S.<unk> , the best-characterized aminoglycoside-modifying enzyme is aminoglycoside adenylyltransferase 4' IA (ANT(4')IA). This enzyme has been solved by X-ray crystallography. The enzyme is able to attach an adenyl moiety to the 4' hydroxyl group of many aminoglycosides, including kamamycin and gentamicin. Glycopeptide resistance is mediated by acquisition of the vanA gene, which originates from the Tn1546 transposon found in a plasmid in enterococci and codes for an enzyme that produces an alternative peptidoglycan to which vancomycin will not bind. Today, S.<unk>  has become resistant to many commonly used antibiotics. In the UK, only 2% of all S.<unk>  isolates are sensitive to penicillin, with a similar picture in the rest of the world. The β-lactamase-resistant penicillins (methicillin, oxacillin, cloxacillin, and flucloxacillin) were developed to treat penicillin-resistant S.<unk> , and are still used as first-line treatment. Methicillin was the first antibiotic in this class to be used (it was introduced in 1959), but, only two years later, the first case of methicillin-resistant<unk>  (MRSA) was reported in England. Despite this, MRSA generally remained an uncommon finding, even in hospital settings, until the 1990s, when the MRSA prevalence in hospitals exploded, and it is now endemic. Now, methicillin-resistant<unk>  (MRSA) is not only a human pathogen causing a variety of infections, such as skin and soft tissue infection (SSTI), pneumonia, and sepsis, but it also can cause disease in animals, known as livestock-associated MRSA (LA-MRSA). MRSA infections in both the hospital and community setting are commonly treated with non-β-lactam antibiotics, such as clindamycin (a lincosamine) and co-trimoxazole (also commonly known as trimethoprim/sulfamethoxazole). Resistance to these antibiotics has also led to the use of new, broad-spectrum anti-Gram-positive antibiotics, such as linezolid, because of its availability as an oral drug. First-line treatment for serious invasive infections due to MRSA is currently glycopeptide antibiotics (vancomycin and teicoplanin). A number of problems with these antibiotics occur, such as the need for intravenous administration (no oral preparation is available), toxicity, and the need to monitor drug levels regularly by blood tests. Also, glycopeptide antibiotics do not penetrate very well into infected tissues (this is a particular concern with infections of the brain and meninges and in endocarditis). Glycopeptides must not be used to treat methicillin-sensitive S.<unk>  (MSSA), as outcomes are inferior. Because of the high level of resistance to penicillins and because of the potential for MRSA to develop resistance to vancomycin, the U.S. Centers for Disease Control and Prevention has published guidelines for the appropriate use of vancomycin. In situations where the incidence of MRSA infections is known to be high, the attending physician may choose to use a glycopeptide antibiotic until the identity of the infecting organism is known. After the infection is confirmed to be due to a methicillin-susceptible strain of S.<unk> , treatment can be changed to flucloxacillin or even penicillin, as appropriate. Vancomycin-resistant S.<unk>  (VRSA) is a strain of S.<unk>  that has become resistant to the glycopeptides. The first case of vancomycin-intermediate S.<unk>  (VISA) was reported in Japan in 1996; but the first case of S.<unk>  truly resistant to glycopeptide antibiotics was only reported in 2002. Three cases of VRSA infection had been reported in the United States as of 2005. At least in part the antimicrobial resistance in S.<unk>  can be explained by its ability to adapt. Multiple two component signal transduction pathways helps S.<unk>  to express genes that are required to survive under antimicrobial stress.
Staphylococcus aureus
Streptococcus bovis
Streptococcus pyogenes
Pseudomonas aeruginosa
Streptococcus
Staphylococcus saprophyticus
Staphylococcus haemolyticus
Bacillus anthracis