Biofilms

Biofilms US Medical PG Question 1: A 37-year-old woman with a history of anorectal abscesses complains of pain in the perianal region. Physical examination reveals mild swelling, tenderness, and erythema of the perianal skin. She is prescribed oral ampicillin and asked to return for follow-up. Two days later, the patient presents with a high-grade fever, syncope, and increased swelling. Which of the following would be the most common mechanism of resistance leading to the failure of antibiotic therapy in this patient?

• A. Intrinsic absence of a target site for the drug
• B. Use of an altered metabolic pathway
• C. Production of beta-lactamase enzyme (Correct Answer)
• D. Altered structural target for the drug
• E. Drug efflux pump

Biofilms Explanation: ***Production of beta-lactamase enzyme*** - The patient's symptoms of a rapidly worsening infection despite ampicillin treatment suggest the presence of a **beta-lactamase producing organism**. Ampicillin is a **beta-lactam antibiotic** that is inactivated by these enzymes. - Anorectal abscesses and rapidly progressing soft tissue infections are often caused by **polymicrobial flora**, including staphylococci and enterococci, many of which can produce **beta-lactamase**. *Intrinsic absence of a target site for the drug* - While some bacteria inherently lack the target site for certain drugs (e.g., mycoplasma lacking a cell wall, thus being resistant to beta-lactams), this is less likely to be the **most common mechanism of acquired resistance** leading to treatment failure in a typical perianal infection. - The rapid progression and failed initial treatment point towards an **acquired mechanism of resistance** rather than an intrinsic one. *Use of an altered metabolic pathway* - This mechanism, such as altered **folate synthesis pathways** in resistance to trimethoprim-sulfamethoxazole, is less common as the primary mechanism for ampicillin resistance. - Ampicillin's mechanism of action primarily targets the **bacterial cell wall**, not a metabolic pathway in the same way. *Altered structural target for the drug* - This involves modifications to the **penicillin-binding proteins (PBPs)**, which are the targets of beta-lactam antibiotics like ampicillin. While a valid mechanism (e.g., in MRSA), the **production of beta-lactamase** is generally a more widespread and common cause of ampicillin failure, especially in infections involving mixed flora from the perianal region. - Given the abrupt failure of ampicillin, **beta-lactamase inactivation** is a more immediate and common cause than a rapid mutational change in PBPs. *Drug efflux pump* - **Efflux pumps** actively remove antibiotics from the bacterial cell, contributing to resistance against various drug classes. - While efflux pumps can play a role, the dominant mechanism for resistance to **ampicillin** in many common perianal pathogens is the **enzymatic degradation by beta-lactamases**.

Biofilms US Medical PG Question 2: Blood cultures are sent to the laboratory and empiric treatment with intravenous vancomycin is started. Blood cultures grow gram-negative bacilli identified as Cardiobacterium hominis. Which of the following is the most appropriate next step in management?

• A. Switch to intravenous gentamicin
• B. Switch to intravenous ampicillin
• C. Switch to intravenous ceftriaxone (Correct Answer)
• D. Switch to intravenous cefazolin
• E. Add intravenous rifampin

Biofilms Explanation: ***Switch to intravenous ceftriaxone*** - **Cardiobacterium hominis** is part of the **HACEK group** of bacteria, which are known for causing **endocarditis**. - These organisms are typically susceptible to **beta-lactam antibiotics**, with **third-generation cephalosporins** like ceftriaxone being the drug of choice due to their excellent activity and good penetration. *Switch to intravenous gentamicin* - While **aminoglycosides** like gentamicin can be used in combination regimens for serious infections, they are generally **not monotherapy** for HACEK endocarditis and are associated with **nephrotoxicity** and **ototoxicity**. - The primary treatment for HACEK endocarditis is a **beta-lactam antibiotic**, not an aminoglycoside alone. *Switch to intravenous ampicillin* - **Ampicillin** is a beta-lactam, but it may not consistently provide optimal coverage for all HACEK organisms, and some strains may have reduced susceptibility. - **Third-generation cephalosporins** are preferred due to their broader and more consistent activity against this group. *Switch to intravenous cefazolin* - **Cefazolin** is a first-generation cephalosporin and typically has **limited activity** against gram-negative bacilli, especially those like Cardiobacterium hominis which require broader-spectrum beta-lactams. - Its spectrum of activity is primarily against **gram-positive bacteria** and some **gram-negative cocci**. *Add intravenous rifampin* - **Rifampin** is primarily used for **mycobacterial infections** and in combination regimens for specific bacterial infections (e.g., bone and joint infections, prosthetic device infections) often due to resistant staphylococci. - It is **not a first-line agent** for Cardiobacterium hominis infections and there's no indication for its use here with an organism susceptible to ceftriaxone.

Biofilms US Medical PG Question 3: A 64-year-old female with type 2 diabetes mellitus comes to the physician because of a 1-week history of painful red swelling on her left thigh. Examination shows a 3- x 4-cm, tender, fluctuant mass. Incision and drainage of the abscess are performed. Culture of the abscess fluid grows gram-positive, coagulase-positive cocci that are resistant to oxacillin. Which of the following best describes the mechanism of resistance of the causal organism to oxacillin?

• A. Degradation of the antibiotic
• B. Decreased uptake of the antibiotic
• C. Decreased activation of the antibiotic
• D. Altered target of the antibiotic (Correct Answer)
• E. Acetylation of the antibiotic

Biofilms Explanation: ***Altered target of the antibiotic*** - The organism described (gram-positive, coagulase-positive cocci, oxacillin-resistant) is **methicillin-resistant *Staphylococcus aureus* (MRSA)**. - MRSA achieves oxacillin (and other beta-lactam) resistance by acquiring the ***mecA* gene**, which encodes for a **modified penicillin-binding protein (PBP2a)** with reduced affinity for beta-lactam antibiotics. *Degradation of the antibiotic* - This mechanism, primarily through the production of **beta-lactamase enzymes**, can degrade beta-lactam antibiotics. - While *Staphylococcus aureus* can produce beta-lactamases, oxacillin (a **penicillinase-resistant penicillin**) is specifically engineered to be stable against these enzymes. *Decreased uptake of the antibiotic* - Reduced permeability of the bacterial cell wall can lead to decreased uptake, a mechanism more commonly associated with **gram-negative bacteria** due to their outer membrane. - This is not the primary mechanism of resistance for MRSA to oxacillin. *Decreased activation of the antibiotic* - Some antibiotics are prodrugs that require activation by bacterial enzymes, and resistance can arise from mutations affecting this activation. - Oxacillin is active in its administered form and does not require bacterial activation. *Acetylation of the antibiotic* - **Enzymatic modification**, such as acetylation, adenylylation, or phosphorylation, is a common mechanism of resistance, particularly against **aminoglycoside antibiotics**. - This specific mechanism is not responsible for oxacillin resistance in MRSA.

Biofilms US Medical PG Question 4: A 65-year-old man presents with low-grade fever and malaise for the last 4 months. He also says he has lost 9 kg (20 lb) during this period and suffers from extreme fatigue. Past medical history is significant for a mitral valve replacement 5 years ago. His temperature is 38.1°C (100.6°F), respirations are 22/min, pulse is 102/min, and blood pressure is 138/78 mm Hg. On physical examination, there is a new onset 2/6 holosystolic murmur loudest in the apical area of the precordium. Which of the following organisms is the most likely cause of this patient’s condition?

• A. Enterococcus (Correct Answer)
• B. Candida albicans
• C. Coagulase-negative Staphylococcus spp.
• D. Escherichia coli
• E. Pseudomonas aeruginosa

Biofilms Explanation: ***Enterococcus*** - This patient has **late prosthetic valve endocarditis (PVE)**, occurring **5 years after mitral valve replacement**. - Late PVE (>1 year post-surgery) is most commonly caused by **viridans streptococci** and ***Staphylococcus aureus***, followed by **Enterococcus species**. - Among the given options, ***Enterococcus*** is the most common cause, particularly in **elderly patients**. - The **subacute presentation** with **4 months of low-grade fever, malaise, weight loss**, and **new-onset murmur** is consistent with enterococcal endocarditis. - Enterococcus is a common cause of healthcare-associated endocarditis and has increased prevalence in patients with prosthetic valves. *Coagulase-negative Staphylococcus spp.* - Coagulase-negative staphylococci (e.g., *S. epidermidis*) are the **most common cause of early PVE** (within the first year after surgery). - At **5 years post-surgery**, this represents **late PVE**, where coagulase-negative staph is much less common than streptococci, *S. aureus*, and enterococci. - While it can occur in late PVE, it is not the most likely organism in this timeframe. *Escherichia coli* - *E. coli* is an uncommon cause of endocarditis, typically associated with underlying gastrointestinal or urinary tract sources. - It generally presents **acutely** rather than with the subacute 4-month course seen here. - Not a typical cause of prosthetic valve endocarditis. *Candida albicans* - Fungal endocarditis is rare and typically seen in **immunocompromised patients, IV drug users**, or those with **prolonged ICU stays** with indwelling catheters. - While *Candida* can cause PVE, it is much less common than bacterial causes in this clinical context. *Pseudomonas aeruginosa* - *Pseudomonas* endocarditis typically occurs in **IV drug users** and commonly affects the **tricuspid valve** (right-sided). - Usually presents as an **acute infection** rather than the subacute presentation here. - Not a common cause of late prosthetic valve endocarditis in non-IVDU patients.

Biofilms US Medical PG Question 5: A 47-year-old woman comes to the physician because of a 6-week history of fatigue and low-grade fever. She has no history of serious illness except for a bicuspid aortic valve, diagnosed 10 years ago. She does not use illicit drugs. Her temperature is 37.7°C (99.9°F). Physical examination shows petechiae under the fingernails and multiple tender, red nodules on the fingers. A new grade 2/6 diastolic murmur is heard at the right second intercostal space. Which of the following is the most likely causal organism?

• A. Staphylococcus epidermidis
• B. Streptococcus pyogenes
• C. Streptococcus sanguinis (Correct Answer)
• D. Streptococcus pneumoniae
• E. Enterococcus faecalis

Biofilms Explanation: ***Streptococcus sanguinis*** - The patient's presentation with **fatigue, low-grade fever, petechiae, tender nodules (Osler nodes)**, and a **new diastolic murmur** in a patient with a **bicuspid aortic valve** is highly suggestive of **infective endocarditis**. - **Streptococcus sanguinis** (and other viridans streptococci) are common causes of subacute bacterial endocarditis, often associated with **oral flora** and pre-existing valvular heart disease. *Staphylococcus epidermidis* - This organism is a common cause of **prosthetic valve endocarditis** and **nosocomial infections** but is less likely to cause endocarditis in a native valve without a history of recent surgery or intravenous lines. - While it can cause endocarditis, the clinical features here, especially the lack of recent medical interventions, point away from *S. epidermidis* as the primary cause. *Streptococcus pyogenes* - **Streptococcus pyogenes** is primarily known for causing **strep throat, scarlet fever, and rheumatic fever**, which can lead to rheumatic heart disease but rarely causes acute or subacute infective endocarditis directly. - It typically causes more acute and severe infections, which doesn't align with the 6-week history of low-grade fever and fatigue. *Streptococcus pneumoniae* - **Streptococcus pneumoniae** is a common cause of **pneumonia, meningitis, and otitis media** but is an uncommon cause of infective endocarditis, accounting for a very small percentage of cases. - Endocarditis due to *S. pneumoniae* tends to be **acute and fulminant**, often associated with severe systemic illness, which is not fully consistent with the subacute presentation here. *Enterococcus faecalis* - **Enterococcus faecalis** is a common cause of **nosocomial urinary tract infections** and can cause endocarditis, especially in older patients or those with gastrointestinal or genitourinary procedures. - While it's a possibility for endocarditis, the oral flora association with viridans streptococci (like *S. sanguinis*) in the context of a bicuspid aortic valve makes it a more direct fit.

Biofilms US Medical PG Question 6: A 59-year-old man presents to the emergency room for a fever that has persisted for over 4 days. In addition, he has been experiencing weakness and malaise. His past medical history is significant for a bicuspid aortic valve that was replaced 2 years ago. Physical exam reveals nailbed splinter hemorrhages, tender nodules on his fingers, and retinal hemorrhages. An echocardiogram shows aortic valve vegetations and culture reveals a gram-positive alpha-hemolytic organism that grows as cocci in chains. The organism is then exposed to optochin and found to be resistant. Finally, they are seen to ferment sorbitol. The most likely cause of this patient's symptoms is associated with which of the following?

• A. Pneumonia
• B. Colon cancer
• C. IV drug use
• D. Dental procedures (Correct Answer)
• E. Sexual activity

Biofilms Explanation: ***Dental procedures*** - The patient's presentation with **infective endocarditis** (fever, weakness, malaise, splinter hemorrhages, Osler nodes [tender nodules], Roth spots [retinal hemorrhages], and valve vegetations) is caused by a gram-positive alpha-hemolytic, optochin-resistant, sorbitol-fermenting coccus in chains. - These microbiologic characteristics identify **viridans group streptococci** (such as *Streptococcus mutans* or *S. sanguinis*), which are **normal oral flora**. - The patient's **prosthetic aortic valve** makes him particularly susceptible to endocarditis, and **dental procedures** can introduce these oral bacteria into the bloodstream, leading to bacteremia and valve seeding. - This is why patients with prosthetic valves require **antibiotic prophylaxis** before dental procedures. *Pneumonia* - While pneumonia can cause fever and malaise, it doesn't lead to the characteristic peripheral stigmata of **endocarditis** like splinter hemorrhages, Osler nodes, or Roth spots, nor valve vegetations. - The organism isolated (alpha-hemolytic, optochin-resistant viridans streptococci) is normal oral flora, not a typical cause of pneumonia. *Colon cancer* - **Colon cancer** is strongly associated with endocarditis caused by ***Streptococcus gallolyticus* (formerly *S. bovis* biotype I)**. - However, the microbiologic description in this case (particularly optochin resistance and sorbitol fermentation) identifies **viridans streptococci**, not *S. gallolyticus*. - If this were *S. gallolyticus* endocarditis, colonoscopy would be indicated to screen for colorectal malignancy. *IV drug use* - **IV drug use** is a major risk factor for **right-sided endocarditis**, particularly involving the **tricuspid valve**, typically caused by ***Staphylococcus aureus***. - This patient has **left-sided** (aortic) **prosthetic valve endocarditis** caused by viridans streptococci, which is not the typical pattern for IV drug use. *Sexual activity* - **Sexual activity** is not a risk factor for **infective endocarditis** caused by viridans streptococci. - While certain sexually transmitted pathogens can rarely cause systemic complications, they do not predispose to endocarditis with oral flora organisms.

Biofilms US Medical PG Question 7: A 3-year-old female is found to have unusual susceptibility to infections by catalase-producing organisms. This patient likely has a problem with the function of which of the following cell types?

• A. Natural killer cells
• B. Eosinophils
• C. B cells
• D. T cells
• E. Neutrophils (Correct Answer)

Biofilms Explanation: ***Neutrophils*** - Catalase-producing organisms, such as *Staphylococcus aureus* or *Aspergillus*, are typically cleared by **phagocytic cells**, specifically **neutrophils**, which use the **respiratory burst** to produce reactive oxygen species. - A defect in neutrophil function, particularly in the **NADPH oxidase enzyme complex** responsible for the respiratory burst, leads to **chronic granulomatous disease (CGD)**, characterized by increased susceptibility to infections by these specific pathogens. *Natural killer cells* - **Natural killer (NK) cells** are primarily involved in the anti-viral and anti-tumor immune responses, recognizing and **killing infected or malignant cells**. - They do not play a primary role in clearing bacterial or fungal infections, especially those caused by catalase-producing organisms. *Eosinophils* - **Eosinophils** are primarily involved in defense against **parasitic infections** and in mediating **allergic reactions**. - Their role in clearing common bacterial or fungal infections is limited. *B cells* - **B cells** are responsible for **humoral immunity**, producing **antibodies** that neutralize pathogens and toxins or opsonize them for phagocytosis. - While antibodies can aid in the clearance of many pathogens, a primary deficiency in B cell function (e.g., agammaglobulinemia) would lead to broad susceptibility to encapsulated bacteria, not specifically catalase-positive organisms. *T cells* - **T cells** are central to **cell-mediated immunity**, recognizing and eliminating intracellular pathogens or directly killing infected cells. - Deficiencies in T cell function (e.g., SCID) lead to severe immunodeficiency with susceptibility to opportunistic infections, but do not specifically point to problems with catalase-producing organisms as the hallmark.

Biofilms US Medical PG Question 8: A 20-year-old woman presents for a follow-up visit with her physician. She has a history of cystic fibrosis and is currently under treatment. She has recently been struggling with recurrent bouts of cough and foul-smelling, mucopurulent sputum over the past year. Each episode lasts for about a week or so and then subsides. She does not have a fever or chills during these episodes. She has been hospitalized several times for pneumonia as a child and continues to struggle with diarrhea. Physically she appears to be underweight and in distress. Auscultation reveals reduced breath sounds on the lower lung fields with prominent rhonchi. Which of the following infectious agents is most likely associated with the recurrent symptoms this patient is experiencing?

• A. Mycobacterium avium
• B. Pseudomonas (Correct Answer)
• C. Histoplasma
• D. Pneumococcus
• E. Listeria

Biofilms Explanation: ***Pseudomonas*** - **Pseudomonas aeruginosa** is a common and opportunistic pathogen in patients with **cystic fibrosis** due to altered mucus secretion and impaired mucociliary clearance. - Recurrent cough, foul-smelling, and **mucopurulent sputum** are classic symptoms of **Pseudomonas** lung infections in CF patients, often leading to chronic colonization and bronchiectasis. *Mycobacterium avium* - While *Mycobacterium avium complex* (MAC) can infect patients with cystic fibrosis, it typically causes a **more indolent and chronic lung disease** rather than recurrent, self-limiting bouts of cough and sputum. - MAC infections are often associated with **nodular or cavitary lesions** on imaging and may require prolonged multidrug therapy. *Histoplasmosis* - **Histoplasmosis** is a fungal infection endemic to certain geographic regions (e.g., Ohio and Mississippi River valleys) and is acquired by inhaling spores. - It's **not a typical or recurrent pathogen** in cystic fibrosis patients in the way bacterial infections are, and its presentation often includes fever, chills, and disseminated disease in immunocompromised individuals. *Pneumococcus* - *Streptococcus pneumoniae* (**Pneumococcus**) is a common cause of **acute bacterial pneumonia** in the general population, including young children. - While CF patients can get pneumococcal infections, the pattern of **recurrent bouts of foul-smelling mucopurulent sputum** without fever and the chronic nature of the lung disease point away from typical acute pneumococcal infection and more towards a chronic colonizer like *Pseudomonas*. *Listeria* - *Listeria monocytogenes* is primarily a cause of **foodborne illness**, leading to gastroenteritis, meningitis, or sepsis, particularly in immunocompromised individuals, pregnant women, and neonates. - It is **not a common respiratory pathogen**, and its presentation does not align with the described recurrent pulmonary symptoms in a cystic fibrosis patient.

Biofilms US Medical PG Question 9: A 45-year-old male presents to his primary care physician complaining of drainage from his left great toe. He has had an ulcer on his left great toe for over eight months. He noticed increasing drainage from the ulcer over the past week. His past medical history is notable for diabetes mellitus on insulin complicated by peripheral neuropathy and retinopathy. His most recent hemoglobin A1c was 9.4%. He has a 25 pack-year smoking history. He has multiple sexual partners and does not use condoms. His temperature is 100.8°F (38.2°C), blood pressure is 150/70 mmHg, pulse is 100/min, and respirations are 18/min. Physical examination reveals a 1 cm ulcer on the plantar aspect of the left great toe surrounded by an edematous and erythematous ring. Exposed bone can be palpated with a probe. There are multiple small cuts and bruises on both feet. A bone biopsy reveals abundant gram-negative rods that do not ferment lactose. The pathogen most likely responsible for this patient’s current condition is also strongly associated with which of the following conditions?

• A. Otitis externa (Correct Answer)
• B. Waterhouse-Friedrichsen syndrome
• C. Gastroenteritis
• D. Toxic shock syndrome
• E. Rheumatic fever

Biofilms Explanation: ***Otitis externa*** - The patient's presentation with a chronic **diabetic foot ulcer** with exposed bone and **gram-negative, non-lactose fermenting rods** on bone biopsy indicates **osteomyelitis** caused by ***Pseudomonas aeruginosa***. - ***Pseudomonas aeruginosa*** is strongly associated with **otitis externa** (swimmer's ear), particularly **malignant otitis externa** in diabetic and immunocompromised patients. - This is a classic association tested on USMLE: *Pseudomonas* causes both diabetic foot osteomyelitis and otitis externa. *Waterhouse-Friedrichsen syndrome* - This syndrome involves adrenal hemorrhage and fulminant sepsis, classically caused by ***Neisseria meningitidis***. - Not associated with *Pseudomonas aeruginosa*. *Gastroenteritis* - Primarily caused by enteric pathogens such as *Salmonella*, *Shigella*, *Campylobacter*, *E. coli*, or viral agents. - *Pseudomonas aeruginosa* is not a typical cause of gastroenteritis. *Toxic shock syndrome* - Caused by exotoxins from ***Staphylococcus aureus*** (TSST-1) or **Group A Streptococcus** (pyrogenic exotoxins). - Not associated with *Pseudomonas aeruginosa*. *Rheumatic fever* - A delayed autoimmune complication of **Group A Streptococcal pharyngitis**. - Not related to *Pseudomonas* infections or diabetic foot ulcers.

Biofilms US Medical PG Question 10: A group of microbiological investigators is studying bacterial DNA replication in E. coli colonies. While the cells are actively proliferating, the investigators stop the bacterial cell cycle during S phase and isolate an enzyme involved in DNA replication. An assay of the enzyme's exonuclease activity determines that it is active on both intact and demethylated thymine nucleotides. Which of the following enzymes have the investigators most likely isolated?

• A. DNA ligase
• B. Telomerase
• C. Primase
• D. DNA topoisomerase
• E. DNA polymerase I (Correct Answer)

Biofilms Explanation: ***DNA polymerase I*** - **DNA polymerase I** possesses **5' to 3' exonuclease activity**, which is crucial for removing **RNA primers** (intact nucleotides) laid down by primase during DNA replication. - This 5' to 3' exonuclease activity also allows it to excise damaged DNA, including DNA containing **demethylated thymine nucleotides**. - It also has 3' to 5' exonuclease activity for proofreading. - **Key distinction:** While DNA polymerase III (the main replicative enzyme) only has 3' to 5' exonuclease activity, DNA polymerase I has **both** 3' to 5' and 5' to 3' exonuclease activities, making it essential for primer removal and DNA repair. *DNA ligase* - **DNA ligase** functions to form a **phosphodiester bond** between adjacent nucleotides to seal nicks in the DNA backbone, but it does not have exonuclease activity. - Its primary role is in joining Okazaki fragments and repairing single-strand breaks. *Telomerase* - **Telomerase** is a specialized reverse transcriptase that extends the telomeres at the ends of eukaryotic chromosomes, but is not present in prokaryotes like *E. coli*. - It uses an RNA template to synthesize DNA, and it lacks exonuclease activity. *Primase* - **Primase** is an RNA polymerase that synthesizes short **RNA primers** on the DNA template, providing a starting point for DNA synthesis. - It is involved in synthesizing primers, not in removing or excising nucleotides, and has no exonuclease activity. *DNA topoisomerase* - **DNA topoisomerases** relieve supercoiling in DNA during replication and transcription by cutting and rejoining DNA strands. - While they act on DNA, their function is to manage topological stress, and they do not exhibit exonuclease activity on nucleotides.

Biofilms Flashcard 1 of 8

Question: Some bacteria secrete a _____, allowing the bacteria to stick to a surface

Answer: biofilm (not glycocalyx)

Biofilms Flashcard 2 of 8

Question: What cause of osteomyelitis is more common in prosthetic joint replacement? _____

Answer: Staphylococcus epidermidis

Biofilms Flashcard 3 of 8

Question: Which bacteria is associated with traumatic open wound infection?_____

Answer: Clostridium perfringens

Biofilms Flashcard 4 of 8

Question: Vibrio _____ is associated with wound infections that contact contaminated seafood or water

Answer: vulnificus

Biofilms Flashcard 5 of 8

Question: Staphylococcus epidermidis forms a protective _____ that allows it to colonize prosthetic devices

Answer: biofilm

Biofilms Flashcard 6 of 8

Question: What organism is responsible for recurrent pulmonary infections in an infant cystic fibrosis patient? _____

Answer: Staphylococcus aureus

Biofilms Flashcard 7 of 8

Question: Which bacteria has a characteristic "tumbling motility" extracellularly?_____

Answer: Listeria monocytogenes

Biofilms Flashcard 8 of 8

Question: glycocalyx

Answer: mediates adherence to surfaces

Extra Information: polysaccharide