Clinical data | |
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Trade names | Fucidin, others |
Other names | Sodium fusidate |
AHFS/Drugs.com | Micromedex Detailed Consumer Information |
Routes of administration | Topical |
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Pharmacokinetic data | |
Bioavailability | 91% oral bioavailability |
Protein binding | 97 to 99% |
Elimination half-life | Approximately 5 to 6 hours in adults |
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PDB ligand | |
CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.027.506 |
Chemical and physical data | |
Formula | C31H48O6 |
Molar mass | 516.719 g·mol−1 |
3D model (JSmol) | |
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Fusidic acid, sold under the brand name Fucidin among others, is a steroid antibiotic that is often used topically in creams or ointments and eyedrops but may also be given systemically as tablets or injections. As of October 2008 [update] , the global problem of advancing antimicrobial resistance has led to a renewed interest in its use. [2]
Fusidic acid is active in vitro against Staphylococcus aureus , [3] most coagulase-positive staphylococci, Beta-hemolytic streptococci, Corynebacterium species, and most clostridium species.[ medical citation needed ] Fusidic acid has no known useful activity against enterococci or most Gram-negative bacteria (except Neisseria, Moraxella, Legionella pneumophila , and Bacteroides fragilis ).[ medical citation needed ] Fusidic acid is active in vitro and clinically against Mycobacterium leprae but has only marginal activity against Mycobacterium tuberculosis .[ medical citation needed ]
One use of fusidic acid is its activity against methicillin-resistant Staphylococcus aureus (MRSA). [4] [ unreliable medical source? ] Although many strains of MRSA remain sensitive to fusidic acid, there is a low genetic barrier to drug resistance (a single point mutation is all that is required), fusidic acid should never be used on its own to treat serious MRSA infection and should be combined with another antimicrobial such as rifampicin when administering oral or topical dosing regimens approved in Europe, Canada, and elsewhere.[ medical citation needed ] However, resistance selection is low when pathogens are challenged at high drug exposure. [5]
Topical fusidic acid is occasionally used as a treatment for acne vulgaris. [6] As a treatment for acne, fusidic acid is often partially effective at improving acne symptoms. [7] However, research studies have indicated that fusidic acid is not as highly active against Cutibacterium acnes as many other antibiotics that are commonly used as acne treatments. [8] Fusidic acid is also found in several additional topical skin and eye preparations (e.g. Fucibet), although its use for these purposes is controversial. [9]
Fucidin tablets and suspension, whose active ingredient is sodium fusidate, occasionally cause liver damage, which can produce jaundice (yellowing of the skin and the whites of the eyes). This condition will almost always get better after the patient finishes taking Fucidin tablets or suspension. Other related side-effects include dark urine and lighter-than-usual feces. These, too, should normalize when the course of treatment is completed. [10]
Fusidic acid acts as a bacterial protein synthesis inhibitor by preventing the turnover of elongation factor G (EF-G) from the ribosome. Fusidic acid is effective primarily on Gram-positive bacteria such as Staphylococcus , Streptococcus [11] and Corynebacterium species.
Fusidic acid is a tetracyclic, naturally occurring steroid derived from the fungus Fusidium coccineum and was developed by Leo Pharma in Ballerup, Denmark and released for clinical use in the 1960s.[ citation needed ] It has also been isolated from Mucor ramannianus and Isaria kogana.[ citation needed ] The drug is licensed for use as its sodium salt sodium fusidate, and it is approved for use under prescription in Australia, Canada, Colombia, the European Union, India, Japan, New Zealand, South Korea, Taiwan, Thailand, and the United Kingdom.[ citation needed ]
Fusidic acid binds to EF-G after translocation and GTP (guanosine-5'-triphosphate) hydrolysis. [12] This interaction prevents the necessary conformational changes for EF-G release from the ribosome, effectively blocking the protein synthesis process. Fusidic acid can only bind to EF-G in the ribosome after GTP hydrolysis. [13] [14]
Since translocation is a part of elongation and ribosome recycling, fusidic acid can block either or both steps of protein synthesis. [15]
Fusidic acid should not be used on its own to treat S. aureus infections when used at low drug dosages. However, it may be possible to use fusidic acid as monotherapy when used at higher doses. [16] The use of topical preparations (skin creams and eye ointments) containing fusidic acid is strongly associated with the development of resistance, [17] and there are voices advocating against the continued use of fusidic acid monotherapy in the community. [9] Topical preparations used in Europe often contain fusidic acid and gentamicin in combination, which helps to prevent the development of resistance.
There is inadequate evidence of safety in human pregnancy. Animal studies and many years of clinical experience suggest that fusidic acid is devoid of teratogenic effects (birth defects), but fusidic acid can cross the placental barrier. [18]
In vitro susceptibility studies of US strains of several bacterial species such as S. aureus, including MRSA and coagulase negative Staphylococcus, indicate potent activity against these pathogens. [19] [20] [21]
Mechanisms of resistance have been extensively studied only in Staphylococcus aureus. The most studied mechanism is the development of point mutations in fusA, the chromosomal gene that codes for EF-G. The mutation alters EF-G so that fusidic acid is no longer able to bind to it. [22] [23] Resistance is readily acquired when fusidic acid is used alone and commonly develops during the course of treatment. As with most other antibiotics, resistance to fusidic acid arises less frequently when used in combination with other drugs. For this reason, fusidic acid should not be used on its own to treat serious Staph. aureus infections. However, at least in Canadian hospitals, data collected between 1999 and 2005 showed rather low rate of resistance of both methicillin-susceptible and methicillin-resistant to fusidic acid, and mupirocin was found to be the more problematic topical antibiotic for the aforementioned conditions. [24]
Some bacteria also display 'FusB-type' resistance, which has been found to be the most prevalent in Staphylococcus spp. in many clinical isolates. [25] [26] [27] This resistance mechanism is mediated by fusB, fusC, and fusD genes found primarily on plasmids, [28] but have also been found in chromosomal DNA. [29] The product of fusB-type resistance genes is a 213-residue cytoplasmic protein which interacts in a 1:1 ratio with EF-G. FusB-type proteins bind in a region distinct from fusidic acid to induce a conformational change which results in liberation of EF-G from the ribosome, allowing the elongation factor to participate in another round of ribosome translocation. [30]
Fusidic acid should not be used with quinolone antibiotics, with which it is antagonistic. Although clinical practice over the past decade has supported the combination of fusidic acid and rifampicin, a recent clinical trial showed that there is an antagonistic interaction when both antibiotics are combined. [31]
On 8 August 2008, it was reported that the Irish Medicines Board was investigating the death of a 59-year-old Irish man who developed rhabdomyolysis after combining atorvastatin and fusidic acid, and three similar cases. [32] In August 2011, the UK's Medicines and Healthcare products Regulatory Agency issued a Drug Safety Update warning that "systemic fusidic acid (Fucidin) should not be given with statins because of a risk of serious and potentially fatal rhabdomyolysis." [33]
An orally-administered mono-therapy with a high loading dose is under development in the United States. [16]
A different oral dosing regimen, based on the compound's pharmacokinetic/pharmacodynamic (PK-PD) profile is in clinical development in the US. [16] as Taksta. [35]
Fusidic acid is being tested for indications beyond skin infections. There is evidence from compassionate use cases that fusidic acid may be effective in the treatment of patients with prosthetic joint-related chronic osteomyelitis. [36]
Staphylococcus aureus is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often positive for catalase and nitrate reduction and is a facultative anaerobe that can grow without the need for oxygen. Although S. aureus usually acts as a commensal of the human microbiota, it can also become an opportunistic pathogen, being a common cause of skin infections including abscesses, respiratory infections such as sinusitis, and food poisoning. Pathogenic strains often promote infections by producing virulence factors such as potent protein toxins, and the expression of a cell-surface protein that binds and inactivates antibodies. S. aureus is one of the leading pathogens for deaths associated with antimicrobial resistance and the emergence of antibiotic-resistant strains, such as methicillin-resistant S. aureus (MRSA), is a worldwide problem in clinical medicine. Despite much research and development, no vaccine for S. aureus has been approved.
Minocycline, sold under the brand name Minocin among others, is a tetracycline antibiotic medication used to treat a number of bacterial infections such as some occurring in certain forms of pneumonia. It is generally less preferred than the tetracycline doxycycline. Minocycline is also used for the treatment of acne and rheumatoid arthritis. It is taken by mouth or applied to the skin.
Clindamycin is a lincosamide antibiotic medication used for the treatment of a number of bacterial infections, including osteomyelitis (bone) or joint infections, pelvic inflammatory disease, strep throat, pneumonia, acute otitis media, and endocarditis. It can also be used to treat acne, and some cases of methicillin-resistant Staphylococcus aureus (MRSA). In combination with quinine, it can be used to treat malaria. It is available by mouth, by injection into a vein, and as a cream or a gel to be applied to the skin or in the vagina.
Mupirocin, sold under the brand name Bactroban among others, is a topical antibiotic useful against superficial skin infections such as impetigo or folliculitis. It may also be used to get rid of methicillin-resistant S. aureus (MRSA) when present in the nose without symptoms. Due to concerns of developing resistance, use for greater than ten days is not recommended. It is used as a cream or ointment applied to the skin.
Trimethoprim/sulfamethoxazole, sold under the brand name Bactrim among others, is a fixed-dose combination antibiotic medication used to treat a variety of bacterial infections. It consists of one part trimethoprim to five parts sulfamethoxazole. It is used to treat urinary tract infections, methicillin-resistant Staphylococcus aureus (MRSA) skin infections, travelers' diarrhea, respiratory tract infections, and cholera, among others. It is used both to treat and prevent pneumocystis pneumonia and toxoplasmosis in people with HIV/AIDS and other causes of immunosuppression. It can be given orally or intravenous infusion.
Vancomycin-resistant Staphylococcus aureus (VRSA) are strains of Staphylococcus aureus that have acquired resistance to the glycopeptide antibiotic vancomycin. Bacteria can acquire resistant genes either by random mutation or through the transfer of DNA from one bacterium to another. Resistance genes interfere with the normal antibiotic function and allow a bacteria to grow in the presence of the antibiotic. Resistance in VRSA is conferred by the plasmid-mediated vanA gene and operon. Although VRSA infections are uncommon, VRSA is often resistant to other types of antibiotics and a potential threat to public health because treatment options are limited. VRSA is resistant to many of the standard drugs used to treat S. aureus infections. Furthermore, resistance can be transferred from one bacterium to another.
Neomycin/polymyxin B/bacitracin, also known as triple antibiotic ointment, is an antibiotic medication used to reduce the risk of infections following minor skin injuries. It contains the three antibiotics neomycin, polymyxin B, and bacitracin. It is for topical use.
Tigecycline, sold under the brand name Tygacil, is a tetracycline antibiotic medication for a number of bacterial infections. It is a glycylcycline class drug that is administered intravenously. It was developed in response to the growing rate of antibiotic resistant bacteria such as Staphylococcus aureus, Acinetobacter baumannii, and E. coli. As a tetracycline derivative antibiotic, its structural modifications has expanded its therapeutic activity to include Gram-positive and Gram-negative organisms, including those of multi-drug resistance.
Flucloxacillin, also known as floxacillin, is an antibiotic used to treat skin infections, external ear infections, infections of leg ulcers, diabetic foot infections, and infection of bone. It may be used together with other medications to treat pneumonia, and endocarditis. It may also be used prior to surgery to prevent Staphylococcus infections. It is not effective against methicillin-resistant Staphylococcus aureus (MRSA). It is taken by mouth or given by injection into a vein or muscle.
Lincosamides are a class of antibiotics, which include lincomycin, clindamycin, and pirlimycin.
A drug of last resort (DoLR), also known as a heroic dose, is a pharmaceutical drug which is tried after all other drug options have failed to produce an adequate response in the patient. Drug resistance, such as antimicrobial resistance or antineoplastic resistance, may make the first-line drug ineffective, especially in case of multidrug-resistant pathogens and tumors. Such an alternative may be outside of extant regulatory requirements or medical best practices, in which case it may be viewed as salvage therapy.
Oritavancin, sold under the brand name Orbactiv among others, is a semisynthetic glycopeptide antibiotic medication for the treatment of serious Gram-positive bacterial infections. Its chemical structure as a lipoglycopeptide is similar to vancomycin.
Cefoxitin is a second-generation cephamycin antibiotic developed by Merck & Co., Inc. from Cephamycin C in the year following its discovery, 1972. It was synthesized in order to create an antibiotic with a broader spectrum. It is often grouped with the second-generation cephalosporins. Cefoxitin requires a prescription and as of 2010 is sold under the brand name Mefoxin by Bioniche Pharma, LLC. The generic version of cefoxitin is known as cefoxitin sodium.
Lysostaphin is a Staphylococcus simulans metalloendopeptidase. It can function as a bacteriocin (antimicrobial) against Staphylococcus aureus.
Beta-lactamases are a family of enzymes involved in bacterial resistance to beta-lactam antibiotics. In bacterial resistance to beta-lactam antibiotics, the bacteria have beta-lactamase which degrade the beta-lactam rings, rendering the antibiotic ineffective. However, with beta-lactamase inhibitors, these enzymes on the bacteria are inhibited, thus allowing the antibiotic to take effect. Strategies for combating this form of resistance have included the development of new beta-lactam antibiotics that are more resistant to cleavage and the development of the class of enzyme inhibitors called beta-lactamase inhibitors. Although β-lactamase inhibitors have little antibiotic activity of their own, they prevent bacterial degradation of beta-lactam antibiotics and thus extend the range of bacteria the drugs are effective against.
Dalbavancin, sold under the brand names Dalvance in the US and Xydalba in the EU among others, is a second-generation lipoglycopeptide antibiotic medication. It belongs to the same class as vancomycin, the most widely used and one of the treatments available to people infected with methicillin-resistant Staphylococcus aureus (MRSA).
Nadifloxacin is a topical fluoroquinolone antibiotic for the treatment of acne vulgaris. It is also used to treat bacterial skin infections.
mecA is a gene found in bacterial cells which allows them to be resistant to antibiotics such as methicillin, penicillin and other penicillin-like antibiotics.
Ceftaroline fosamil (INN), brand name Teflaro in the US and Zinforo in Europe, is a cephalosporin antibiotic with anti-MRSA activity. Ceftaroline fosamil is a prodrug of ceftaroline. It is active against methicillin-resistant Staphylococcus aureus (MRSA) and other Gram-positive bacteria. It retains some activity of later-generation cephalosporins having broad-spectrum activity against Gram-negative bacteria, but its effectiveness is relatively much weaker. It is currently being investigated for community-acquired pneumonia and complicated skin and skin structure infection.
SCCmec, or staphylococcal cassette chromosome mec, is a mobile genetic element of Staphylococcus bacterial species. This genetic sequence includes the mecA gene coding for resistance to the antibiotic methicillin and is the only known way for Staphylococcus strains to spread the gene in the wild by horizontal gene transfer. SCCmec is a 21 to 60 kb long genetic element that confers broad-spectrum β-lactam resistance to MRSA. Moreover, additional genetic elements like Tn554, pT181, and pUB110 can be found in SCCmec, which have the capability to render resistance to various non-β-lactam drugs.
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