CA- MRSA CURRENT PERCEPTIONS ON TREATMENT

Dr.T.V.Rao MD Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a major public health threat. Every hospital using Diagnostic Microbiology services find few reports with MRSA reported. The challenge to the clinical microbiology laboratory is how to respond to the MRSA problem, in particular to CA-MRSA. Yet in our laboratories with poor infrastructure we will mark isolate as just MRSA, and without putting much thought on CA-MRSA, as there is upraise of Community associated MRSA ( CA-MRSA,) By the CDC’s definition, CA- MRSA infection is classified as community-associated in individuals who have not been hospitalized or undergone a medical procedure within the past 12 months. Previously, infection with MRSA typically occurred in hospitalized patients, known as health care-associated MRSA infection (HA-MRSA). As we all know that in the late 1990s, dramatic increases in the frequency of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections were noted among children without established risk factors for MRSA infections other differences between HA-MRSA and CA-MRSA exist. Fortunately, CA-MRSA isolates are usually susceptible to more antibiotic agents than HA-MRSA isolates, which tend to be resistant to multiple antibiotics. CA-MRSA isolates are more likely to produce specific virulence factors or exotoxins. An important virulence factor produced by many MRSA strains is Panton-Valentine leukocidin (PVL), a cytotoxin. Infection with a PVL-producing strain can result in serious clinical illness, such as osteomyelitis or haemorrhagic necrotizing pneumonia. In the recent past at our hospital we are getting at least 3-5 isolates as MRSA with simple marker of identification being resistant to Cefoxitin, many times we are all limited by using human blood however I find when you wish to test MRSA we should prefer to use mannitol salt agar was added to the inoculation media for the detection of MRSA .Genotypes of CA-MRSA strains are distinct from HA-MRSA isolates. The mecA gene in staphylococci is responsible for resistance to beta-lactam antibiotics. The mecA gene is transported on a mobile genetic element known as a staphylococcal cassette chromosome (SCC). Five SCCmec complex types have been found for Staphylococcus aureus. Another important characteristic differentiating CA-MRSA strains from HA-MRSA strains is the production of unique toxins and virulence factors. Analyses have revealed differing genes and toxins isolated from CA-MRSA strains that have not been found in HA-MRSA

isolates. A clinically significant virulence factor unique to CA-MRSA strains is the PVL toxin. This cytotoxin damages human leukocytes and can produce severe tissue necrosis. Case reports of previously healthy children and adults affected with CA-MRSA infection and the resulting necrotic clinical manifestations, Although the true prevalence of PVL toxin production in CA-MRSA is not known, some reports indicate that the majority of CA-MRSA isolates are able to secrete this highly potent toxin. The most common CA-MRSA clone circulating in the United States, USA300, carries the genes encoding PVL. However, the USA 300 CA-MRSA clone is being increasing recognized as a nosocomial pathogen and so the molecular characteristics of CA-MRSA and HA-MRSA strains are becoming blurred.

Antibiotic treatment of CA-MRSA Due to the genotypic differences described above, CA-MRSA isolates are primarily resistant to beta-lactam antibiotics (penicillin’s, cephalosporins, and carbapenems) and macrolides. Thus, additional treatment options are available to clinicians treating CA-MRSA infection. Many clinicians jump to use Vancomycin the best for use in MRSA well reviewed studies indicate, Oral antibiotic choices most likely to be used by paediatric clinicians include clindamycin, trimethoprim-sulfamethoxazole, doxycycline, minocycline, rifampin and linezolid. Data describing the effectiveness of these agents in children with CA-MRSA. Documentation of the effectiveness of TMP-SMX comes from case reports and anecdotal recommendations. Sensitivity studies documenting the susceptibility of CA-MRSA to TMP-SMX should be obtained with its use. Because TMP-SMX contains a sulphonamide antibiotic, it should not be used in children with a history of a documented true allergic reaction to previous sulphonamide use. As CA-MRSA infection may also occur in new-borns, caution should be used when prescribing TMP-SMX in these patients. As TMP-SMX may displace bilirubin from albumin binding sites, this antibiotic should not be used in new-borns with increased bilirubin, next option being Clindamycin is another antibiotic frequently recommended as an initial therapeutic option. Most CA-MRSA isolates are susceptible to clindamycin. However, it is important that inducible resistance be tested for when using clindamycin, Clindamycin should not be used if the D-test is positive, which indicates inducible resistance. Clindamycin is a viable option for infants aged younger than 2 months with CA-MRSA infection, Vancomycin is generally considered the drug of choice for severe CA-MRSA infections. Although MRSA is usually sensitive to vancomycin, strains with intermediate susceptibility, or, more rarely, resistant strains have

been reported. Linezolid is a unique antibiotic, a member of the oxazolidinone class. Linezolid provides good in vitro activity toward MRSA, although resistance has been reported. Data on its use and effectiveness in treating CA-MRSA are limited, Doxycycline and minocycline have been reported in a small number of adult case reports to be effective therapy for MRSA infection, including skin and soft tissue infections caused by CA-MRSA. In conclusion we are many treating the cases of CA-MRSA without much rationalism we all should know CA-MRSA has more possibilities to produce the toxin which needs more proof, an important theoretical but unproven beneficial effect of linezolid and clindamycin may be the ability of these agents to modify CA-MRSA toxin production. A case report published in 2005 (Micek) described four adults with severe respiratory CA-MRSA infection, in which all the isolates were positive for PVL. Three patients failed therapy with vancomycin but responded to linezolid or clindamycin. As linezolid and clindamycin both function to inhibit protein synthesis, this mechanism may be valuable in modifying exotoxin production. Rifampin may possess good in vitro activity toward CA-MRSA. Case reports have been published describing the use of rifampin in combination with another antibiotic, such as TMP-SMX, clindamycin, or doxycycline/minocycline.it is important to know when the clinicians find their patients not responding to Vancomycin and Linezolid they should consider the lesser tested and prescribed drugs as Clindamycin and TMP-SMX as in most laboratories we do not have facilities to differentiate HA-MRSA from CA-MRSA by Molecular methods. Unless we establish better facilities in our Departments our reports many not serve the true purpose of optimal treatments in cases of MRSA.

Ref (Web resources from CDC)

Dr.T.V.Rao MD Professor of Microbiology Freelance write