Hashim Siddique

Sap ID: 70105507

Case study of Microbiology

A 63-year-old man has been hospitalized for 21 days for the management of newly
diagnosed leukemia. Three days after the patient entered the hospital, a urinary tract
infection with Escherichia coli developed. He was treated for 14 days with broad-
spectrum antibiotics. On day 21 of his hospital stay, the patient experienced fever and
shaking chills. Within 24 hours he became hypotensive, and ecthymic skin lesions
appeared. Despite aggressive therapy with antibiotics, the patient died. Multiple blood
cultures were positive for another suspected infection with pathogen.

Q.No.1: What could be the possible pathogen?

Answer: Based on the clinical presentation and the sequence of events described, a
possible pathogen responsible for the suspected infection in this case is methicillin-
resistant Staphylococcus aureus (MRSA).

The development of fever, shaking chills, hypotension, and ecthymic skin lesions after
a prolonged hospital stay and antibiotic treatment raises concerns for a severe
infection, such as sepsis. MRSA is a notorious multidrug-resistant bacterium
commonly associated with healthcare-associated infections. It can cause severe
infections, including bloodstream infections and skin and soft tissue infections.

To confirm the identity of the pathogen, further laboratory testing, such as culture and
sensitivity testing of the blood cultures, would be necessary. Additionally, molecular
techniques like polymerase chain reaction (PCR) can be employed to detect the
presence of specific pathogens, including MRSA.

Q.No.2: What factors put this man at increased risk for Co-infection?

Answer: Several factors put this man at an increased risk for co-infection:

a. Prolonged hospitalization: The patient's extended hospital stay increases the

likelihood of exposure to various pathogens present in the hospital
environment.

b. Leukemia and immunosuppression: The patient's newly diagnosed leukemia

and the subsequent treatment likely compromised his immune system,
making him more susceptible to infections, including co-infections.

c. Urinary tract infection: The previous urinary tract infection caused by

Escherichia coli indicates an increased vulnerability to bacterial infections.
Q.No.3: What virulence factors possessed by the organism make it a
particularly serious pathogen? What are the biologic effects of these
factors? 

Answer: The virulence factors possessed by methicillin-resistant Staphylococcus

aureus (MRSA) and their biologic effects:
MRSA is a strain of Staphylococcus aureus that has developed resistance to
methicillin and other beta-lactam antibiotics. It possesses several virulence factors that
contribute to its pathogenicity and make it a particularly serious pathogen. Some of
the key virulence factors of MRSA include:

1. Cell surface adhesins: MRSA produces adhesins, such as fibronectin-binding

proteins and collagen-binding proteins, which enable the bacteria to attach to
host tissues. This facilitates the establishment of infection and colonization.
2. Exotoxins: MRSA can produce various exotoxins, including Panton-Valentine
leukocidin (PVL) and alpha-hemolysin. PVL is particularly notable for its
ability to destroy white blood cells, leading to tissue damage and impaired host
immune responses. Alpha-hemolysin disrupts host cell membranes, causing
cell death and tissue destruction.
3. Biofilm formation: MRSA has the ability to form biofilms, which are complex
communities of bacteria encased in a protective matrix. Biofilms enhance
bacterial survival, resistance to antibiotics, and evasion of the immune system.
This can lead to persistent infections that are difficult to eradicate.
4. Enzymes: MRSA produces various enzymes, such as coagulase and proteases,
which contribute to its pathogenicity. Coagulase helps the bacteria evade host
immune responses by converting fibrinogen to fibrin, which forms a protective
barrier around the bacteria. Proteases can degrade host proteins, disrupt
immune responses, and contribute to tissue damage.

The biologic effects of these virulence factors include tissue invasion, destruction of
host cells, evasion of host immune responses, and the ability to form persistent
infections. They contribute to the severity of MRSA infections and the challenges
associated with their treatment.

Q.No.4: What three mechanisms are responsible for the antibiotic

resistance found in Pathogen ?

Answer: Methicillin-resistant Staphylococcus aureus (MRSA) has developed

resistance to multiple antibiotics, including methicillin and other beta-lactam
antibiotics. The antibiotic resistance in MRSA is primarily mediated by three main
mechanisms:
1. Penicillin-binding protein (PBP) alteration: MRSA acquires a modified
penicillin-binding protein, known as PBP2a or PBP2' (encoded by the mecA or
mecC gene), which has a low affinity for beta-lactam antibiotics. This altered
 PBP allows the bacteria to continue cell wall synthesis despite the presence of
beta-lactam antibiotics, rendering them ineffective.
2. Production of beta-lactamase enzymes: MRSA can produce beta-lactamase
enzymes, such as the penicillinase enzyme encoded by the blaZ gene. These
enzymes hydrolyze beta-lactam antibiotics, including penicillins and
cephalosporins, breaking down their structure and rendering them ineffective
against the bacteria.
3. Efflux pumps: MRSA possesses efflux pumps, such as the MepA and NorA
pumps, which actively pump out antibiotics from the bacterial cell. These
efflux pumps play a role in reducing the intracellular concentration of
antibiotics, making it more difficult for the drugs to reach their target sites and
exert their antibacterial effects.
4. Altered target sites: Bacteria can undergo genetic mutations or acquire
resistance genes that alter the target sites of antibiotics, making them less
susceptible to the drugs.

The combination of altered PBPs, beta-lactamase production, and efflux pumps

contributes to the high level of antibiotic resistance seen in MRSA strains. These
mechanisms work together to protect the bacteria from the bactericidal effects of beta-
lactam antibiotics, limiting the effectiveness of these drugs in treating MRSA
infections.

Q.No.5: What antibiotics can be used to treat these infections of MRSA?

Answer:  Methicillin-resistant Staphylococcus aureus (MRSA) infections can be

challenging to treat due to the bacterium's resistance to many commonly used
antibiotics. However, there are several antibiotics that are generally effective against
MRSA. The choice of antibiotic depends on the severity and type of infection, as well
as the local antibiotic susceptibility patterns. Some antibiotics commonly used to treat
MRSA infections include:

1. Vancomycin: Vancomycin is a glycopeptide antibiotic that is often considered

the drug of choice for severe MRSA infections. It is administered intravenously
and has good activity against MRSA. However, some strains of MRSA have
shown reduced susceptibility to vancomycin, necessitating alternative treatment
options.
2. Linezolid: Linezolid is an oxazolidinone antibiotic that is effective against
MRSA. It can be administered intravenously or orally, making it suitable for
both hospitalized and outpatient settings. Linezolid is often used as an
alternative when vancomycin is not suitable or in cases of vancomycin-resistant
MRSA.
3. Daptomycin: Daptomycin is a cyclic lipopeptide antibiotic with activity against
MRSA. It is usually given intravenously and is effective against skin and soft
tissue infections caused by MRSA.
 4. Trimethoprim-sulfamethoxazole (TMP-SMX): TMP-SMX is a combination
antibiotic that is active against MRSA. It can be used for mild to moderate
MRSA infections, including skin and soft tissue infections.
5. Clindamycin: Clindamycin is a lincosamide antibiotic that is active against
MRSA. It can be used for certain types of MRSA infections, such as skin and
soft tissue infections. However, it is important to perform susceptibility testing
to ensure the MRSA strain is susceptible to clindamycin, as resistance can
occur.

It is important to note that the choice of antibiotics should be guided by the specific
susceptibility profile of the MRSA strain and local guidelines. The decision should be
made in consultation with an infectious disease specialist to ensure appropriate and
effective treatment.