Question

1. A 55-year-old man presents with many pimples and some larger puss-filled boils on their lower arms and hands. The patient is in pain and has redness around the infected site. The doctor is quick to categorize it is a Staph infection, but the patient comments that they have already been on two rounds of antibiotics, and wants a second opinion, since the infection has persisted.
   1. Why did the infection persist after two rounds of antibiotics?  
   2. What type of clinical diagnostic test would be used to verify the species of microorganism?
   3. How would you obtain a sample from the patient and prepare it for testing?
   4. Hypothesize what medications were first given, and their mode of action, and speculate what medications should be utilized, and how their mode of action and effective will differ.

Answer 1

·Furunculosis is a deep infection of the hair follicle leading to abscess formation with accumulation of pus and necrotic tissue.

· Furuncles appear as red, swollen, and tender nodules on hair-bearing parts of the body, and the most common infectious agent is Staphylococcus aureus, but other bacteria may also be causative. In some countries, methicillin resistant S. aureus is the most common pathogen in skin and soft tissue infections which is problematic since treatment is difficult.

1.       The reason why infection persisted even after two rounds of antibiotics is because of recurrent furunculosis it is generally defined as three or more attacks within a 12 month period.

Colonization of S. aureus in the anterior nares plays a definite role in the etiology of chronic or recurrent furunculosis.

Besides the nares, colonization also occurs in warm, moist skin folds such as behind ears, under pendulous breasts, and in the groin. Bacteria other than S. aureus may also be pathogenic, especially for furuncles in the vulvovaginal and perirectal area, and on the buttocks.

Especially, enteric species such as Enterobacteriaceae and Enterococci are often present at these sites. Corynebacterium, S. epidermidis, and S. pyogenes may also be present in furunculosis.

Immunodeficiency is rarely the primary cause.

There is a decreased quality of life was found in MRSA positive patients who were isolated in palliative institutions and in patients with other recurrent boil diseases like hidradenitis suppurativa.

2.       The diagnosis of furunculosis is relatively straight forward. The microbial agent can be identified with simple cultured swabs. A general clinical examination should be performed, and investigations not only involve culture swabs of the lesions (preferably from pus or fluids from fluctuant boils, eventually obtained by incision) but also of the carrier sites such as nostrils and perineum. Depending on the history, culture swabs of the family members may be relevant. It is suggested to investigate urine and blood glucose, or glycated hemoglobin (HbA1c) to identify any underlying diabetes, and a full blood count to exclude systemic infection or other internal disease. Immunological evaluation may be considered in recurrent disease or signs of internal disease.

3.       Recurrent furunculosis is most often caused by methicillin susceptible S. aureus. Some strains of MRSA, particularly the CA-MRSA, produce a toxin named Panton-Valentine leukocidin (PVL) and are associated with severe infections. PVL is leucocidal, and severe but rare complications such as necrotizing fasciitis and necrotizing pneumonia are described following soft tissue infection with MRSA. PVL is a virulence factor of S. aureus which correlates with chronic recurrent furunculosis.

Infections caused by PVL strains of S.aureus normally cause pus-producing skin infections (e.g. abscesses, boils, carbuncles) and cellulitis. However on rare occasions , they can lead to more invasive infections. Locally patients and families suffering recurrent boils/abscesses without prior skin trauma is the most common presentation. Black top charcoal swabs or Eswabs should be used for sampling and the request form should clearly state if PVL screen is required.

Sample is obtained by cultured swab method. Methicillin-resistant Staphylococcus aureus (MRSA) are strains of Staphylococcus aureus, or "staph," bacteria that are resistant to the antibiotic methicillin as well as to related beta-lactam antibiotics, such as oxacillin, penicillin, amoxicillin, and cephalosporins, that are used to treat ordinary staph infections. MRSA testing detects the presence of MRSA in a patient's sample.

Bacterial culture - a nasal swab is collected from the nares (nostrils) of an asymptomatic person and cultured (put onto a special nutrient medium, incubated, and then examined for the growth of characteristic MRSA colonies). A swab may be collected from a wound site or skin lesion of a person who has been previously treated for a MRSA infection and cultured similarly. A screening culture identifies the absence or presence of MRSA and usually takes 1 to 2 days for a result.

Molecular tests for MRSA screening can detect nasal or wound carriage within hours, allowing for prompt treatment as necessary. The same specimen types are used in a molecular test, but the specimen is analyzed for the genetic markers to identify S. aureus and the mecA gene that confers resistance to methicillin, oxacillin, nafcillin, dicloxacillin, and other similar antibiotics. Molecular MRSA screening is becoming more widespread.

4.       Methicillin, Oxacillin, Nafcillin, Dicloxacillin etc are first given medications.

Mode of Action:

Different antibiotics have different modes of action, owing to the nature of their structure and degree of affinity to certain target sites within bacterial cells.  

Inhibitors of cell wall synthesis. While the cells of humans and animals do not have cell walls, this structure is critical for the life and survival of bacterial species. A drug that targets cell walls can therefore selectively kill or inhibit bacterial organisms. Examples: penicllins, cephalosporins, bacitracin and vancomycin.

Inhibitors of cell membrane function. Cell membranes are important barriers that segregate and regulate the intra- and extracellular flow of substances. A disruption or damage to this structure could result in leakage of important solutes essential for the cell’s survival. Because this structure is found in both eukaryotic and prokaryotic cells, the action of this class of antibiotic are often poorly selective and can often be toxic for systemic use in the mammalian host. Most clinical usage is therefore limited to topical applications. Examples: polymixin B and colistin.

Inhibitors of protein synthesis. Enzymes and cellular structures are primarily made of proteins. Protein synthesis is an essential process necessary for the multiplication and survival of all bacterial cells. Several types of antibacterial agents target bacterial protein synthesis by binding to either the 30S or 50S subunits of the intracellular ribosomes. This activity then results in the disruption of the normal cellular metabolism of the bacteria, and consequently leads to the death of the organism or the inhibition of its growth and multiplication. Examples: Aminoglycosides, macrolides, lincosamides, streptogramins, chloramphenicol, tetracyclines.

Inhibitors of nucleic acid synthesis. DNA and RNA are keys to the replication of all living forms, including bacteria. Some antibiotics work by binding to components involved in the process of DNA or RNA synthesis, which causes interference of the normal cellular processes which will ultimately compromise bacterial multiplication and survival. Examples: quinolones, metronidazole, and rifampin.

Inhibitors of other metabolic processes. Other antibiotics act on selected cellular processes essential for the survival of the bacterial pathogens.    For example, both sulfonamides and trimethoprim disrupt the folic acid pathway, which is a necessary step for bacteria to produce precursors important for DNA synthesis. Sulfonamides target and bind to dihydropteroate synthase, trimethophrim inhibit dihydrofolate reductase; both of these enzymes are essential for the production of folic acid, a vitamin synthesized by bacteria, but not humans.

Medications that should be used for decolonization:

Topical attempts at decolonizing with mupirocin and chlorhexidine can reduce the incidence of subsequent S. aureus infections although with variable efficacy.

Oral antimicrobial therapy is recommended for the treatment of active infection only and is not routinely recommended for decolonization.

An oral agent in combination with rifampicin, if the strain is susceptible, may be considered for decolonization if infections recur despite the above mentioned topical measures. Rifampicin monotherapy is at risk of selecting resistant variants and is not recommended.

The combination of topical and systemic antimicrobials is highly effective with a clearance rate of 87% in treated patients.

Rectal swab cultures may be considered in refractory cases since the gastrointestinal tract may be a reservoir of methicillin susceptible S. aureus and MRSA. In these cases, oral vancomycin (1 g twice daily for 5 days) can eradicate 80%–100% of MRSA gut colonization. Urogenital and vaginal colonization may also appear.