Recent headlines have highlighted the spread of MRSA infection in the United States. According to the CDC, MRSA is responsible for over 90,000 serious infections and over 18,000 hospital stay-related deaths per year in the United States. These MRSA strains are responsible for many serious skin and soft tissue infections, as well as pneumonia. One major problem with MRSA is that occasionally the skin infection can spread to other organs of the body with more severe, life-threatening symptoms, including necrotizing fasciitis (hence the name ‘‘flesh-eating’’ bacteria) and necrotizing pneumonia (tissue destruction), followed by sepsis and toxic shock, and then death in up to 50% of cases. A striking finding about these infections is that they occur even in young immunocompetent patients who were previously healthy. MRSA is resistant to several commonly prescribed antibiotics that are usually effective against gram-positive bacteria (methicillin, penicillin, and cephalosporins), and an infection with a MRSA strain can be deadly if left untreated. MRSA is subcategorized as community acquired (CA-MRSA) or hospital acquired (HAMRSA), depending on how the infection is usually acquired. Most CA-MRSA strains are still sensitive to many antibiotics, such as trimethoprim, tetracycline, and clindamycin, but HA-MRSA strains are often resistant to these drugs while still sensitive to vancomycin and linezolid.
A. Provide a common mechanism that accounts for the observed resistance of MRSA to methicillin, penicillin, and cephalosporin. Provide two different strategies that could be used to overcome this particular resistance.
B. For each of the antibiotics trimethoprim, tetracycline, and clindamycin, provide a possible mechanism to account for the observed resistance of HAMRSA to the antibiotic. Provide a strategy that could be used to treat patients infected with HAMRSA resistant to these antibiotics.
C. Why would HA-MRSA strains that are resistant to methicillin, penicillin, cephalosporins, trimethoprim, tetracycline, and clindamycin still show sensitivity to vancomycin and linezolid? D. Although CA-MRSA is resistant to clindamycin, treatment with clindamycin in combination with rifampin results in an increase in the 50% lethal dose (LD50) value from 10 without antibiotic treatment to 104 with rifampin to 108 for combined treatment with clindamycin and rifampin. In addition, treatment with clindamycin enhanced opsonization of CA-MRSA by macrophages. What possible mechanism(s) could account for these observations (i.e., change in the LD50 value and enhanced opsonization)? Provide your rationale. Provide an experiment that could be performed to confirm your hypothesis.