Infectious Diseases

Question 1

What are the risk factors for pathogens resistant to usual therapy for CAP?

Answer 1

Hospitalisation >days in prev 90 days

Use of ABs in prev 90 days

Immunosuppression

Nonambulatory status

Tube feedings

Gastric acid suppression

Severe COPD or bronchiectasis

Question 2

What is the most common way bacteria enters the lungs, what are two uncommon ways?

Answer 2

Aspiration from the oropharynx is the most common way micro-organisms gain access to the lower respiratory tract. Rarely, it can occur from haematogenous spread e.g. tricuspid endocarditis, or by contiguous extension (touching borders) from infected pleural or mediastinal space.

Question 3

1) What are the 5 most common causes of CAP?
2) What other causes of CAP are possible in: a) Non-ICU hospital patient and b) ICU patient?

Answer 3

1-Steptococcus pneumoniae, Mycoplasma pneumoniae, Haemophilus influenza, Chlamydia pneumoniae, Respiratory viruses

2a) Legionella spp and all of the above
2b) Staphylococcus aureus, Gram-negative bacilli and Steptococcus pneumoniae, Legionella spp, Haemophilus influenza & Respiratory viruses as above

Question 4

1) Describe the pathogens included in:
a) ‘typical’ and
b) ‘atypical’ categories of pneumonia
2) Why is the consideration of atypical pathogens important?

Answer 4

1a) Typical pathogens: S. pneumoniae, Haemophilus influenzae, S. aureus and gram -tive bacilli such as Klebsiella pneumoniae and Pseudomonas aeruginosa
b) Atypical: Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella, respiratory viruses e.g influenza viruses, adenoviruses, human metapneumovirus, and respiratory syncytial viruses
2) Because there are significant implications for treatment. Atypical pathogens are intrinsically resistant to all B-lactam agents and must be treated with a macrolide (Azithromycin/Clarithromycin/Erythomycin), a fluoroquinolone (Ciprofloxacin/Moxifloxacin/Norfloxacin/Ofloxacin), or tetracycline (Doxycycline/Minocycline).

NB: In 10-15% of CAP cases that are polymicrobial, the aetiology usually includes a combination of typical and atypical pathogens.

Question 5

1) What is the common pathogen causing anaerobic pneaumia and what are the possible causative reasons?
2) How do anaerobic bacteria complicate pneumonia?

Answer 5

1) S. aureus pneumonia may complicate influenza infection, including MRSA. Risks include aspiration that has occurred days/weeks before presentation of pneumonia, unprotected airway (alcohol, drug OD or seizure) and significant gingivitis.
2) Complicated by abscess formation and significant empyemas or parapneumonic effusions

NB: In >50% of cases a specific causative organism is never confirmed.

Question 6

a) What are the risk factors for CAP?
b) What are the risk factors for pneumococcal pneumonia?
c) What conditions are at increased risk of P. aeruginosa?
d) What conditions are at increased risk of Legionella?

Answer 6

a) Alcoholism, asthma, immunosuppression, institutionalization & >70 yo.
b) Dementia, seizure disorders, heart failure, cerebrovascular disease, alcoholism, tobacco smoking, COPD and HIV.
c) Severe structural lung disease e.g. bronchiectasis, CF, or severe COPD
d) Diabetes, haematologic malignancy, cancer, severe renal disease, HIV infection, smoking, male gender, recent hotel stay or ship cruise.

Question 7

a) What are the primary clinical symptoms of a patient with pneumonia?
b) What are some associated GP symptoms?
c) What are the common vague associated symptoms?

Answer 7

a) Febrile (chills/sweats/rigors), tachycardia, cough (nonproductive/productive cough-mucoid, purulent, blood-tinged), Dyspnoeic, pleuritic chest pain.
b) Nausea/vomiting &/or diarrhoea
c) Fatigue, headache, myalgias, and arthralgias

Question 8

a) What are some physical examination findings for a patient with pneumonia?
b) How can the presentation of pneumonia change in the elderly?
c) What are the cardiac risks due to pneumonia?
d) In pneumococcal CAP, why is there added risk for cardiac events?

Answer 8

a) Increased RR and WOB. Palpation may reveal increased/decreased tactile/vocal fremitus (vibration intensity felt on the chest wall over areas of increased density/inflammation), dull/flat percussion (due to consolidation or pleural fluid respectively), crackles, bronchial breath sounds &/or pleural friction rub on auscultation.
b) New or worsening confusion.
c) Cardiac complications are enhanced due to inflammation and procoagulant activity-MI, congestive HF, arrhythmias
d) Due to pneumolysis, which increases platelet activation.

NB: Up to 90% of ACS occur in the first week of CAP, with a risk for new-onset congestive HF in elderly up to 1 year.

Question 9

a) What are some ddx when considering pneumonia?
b) What is the primary imaging used to differentiate pneumonia from other causes?
c) What differences on CXR may indicate aetiology?
d) What other imaging may be of value when differentiating pneumonia and why?

Answer 9

a) Chronic bronchitis, heart failure, PE, hypersensitivity pneumonitis, and/or radiation pneumonitis.
b) CXR
c) Pneumatoceles (gas filled cystic spaces on CXR which may have a fluid level) suggest infection with S. aureus. Upper lobe cavitating lesion suggests TB.
d) CT Chest may be of value with suspected post-obstructive pneumonia caused by tumour/foreign body/cavitary disease. CTPA can also be used if suspecting PE.

Question 10

a) What are some pathology tests for diagnosing pneumonia/isolating pathogens?

Answer 10

a) Sputum MCS (difficult to obtain adequate sample, in ICU-intubated patients with deep suction aspirate or bronchoalveolar lavage has a high yeild on culture).

Blood Cultures (prior to AB therapy)

Urinary antigen tests

PCR (respiratory virus infection, Legionella, M. pneumoniae, C.pneumoniae, and mycobacteria).

Serology (atypical organisms such as Coxiella burnetii)

Biomarkers e.g. CRP and PCT

Question 11

a) State the variables of the CURB-65
b) In terms of admission, how can the scoring system be interpreted.

Answer 11

a) Confusion, Urea >7mmol/L, RR >30, SBP <90/DBP <60, _>65_yrs
b) Patients whom score 0 can be treated with OABs at home.

Patients who score 1 or 2 could be hospitalised unless the score is entirely or part due to age.

3 or more patient requires admission and ?ICU

Question 12

1- In general, when are bacteriostatic agents effective, and when are bacteriocidal agents preferred?

2-What are the 5 main mechanisms in which antibacterial agents act?

Answer 12

1-Bacteriostatic agents is effective when host defenses are sufficient.

-Bactericidal agent is preferred with impaired host defenses (e.g neutropenia) or at body sites with limited host defenses (e.g meningitis and endocarditis).

2-Inhibition of cell wall synthesis: B-lactam, Glycopeptides/Lipoglycopeptides, Bacitracin (topical) and Fosfomycin.

• Inhibition of Protein Synthesis: Aminoglycosides, Tetracyclines and Glycylcycline, Macrolides and Ketolides, Lincosamides, Streptogramins, Chlormphenicol, Oxazolidinones, Mupirocin (pseudomonic acid) used topically.
• Inhibition of Bacterial Metabolism: Sulphonamides, Trimethoprim.
• Inhibition of DNA and RNA Synthesis or Activity: Quinolones, Rifamycins, Nitrofurantoin, Metronidazole.
• Disruption of Membrane Integrity: Polymyxins, Daptomycin.

Question 13

1-What is bioavailability and what is an example of antimicrobials with good bioavailability?

2-How can antimicrobials affect CYP enzymes?

3-What are 5 sites of infection where specific antimicrobials must be considered for their penetration?

Answer 13

1-Bioavailability is the percentage of a drug that is absorbed. Agents with high bioavailability incl metronidazole, levofloxacin, and linezolid. IV and oral dosing for highly bioavailable agents usually give equivalent results.

2-Antibacterials can be substrates, inhibitors, or inducers of particular CYP enzymes. e.g. Rifampin is an inducer, increasing production of CYP enzymes and consequently increasing the metabolism of other drugs.

3-Meningitis (penetration through BBB and reach adequate conc in CSF), osteomyelitis, prostatitis, intraocular infections and abscesses. Drainage &/or debridement must be considered to reduce barriers to ABs.

Question 14

1-What are antibacterial considerations for asplenic patients and those with deficits in immune function? e.g. neutropenia

2-What are the most common adverse effects to: B-Lactams, Vancomycin, Aminoglycosides, Fluoroquinolones, Rifampin, Tetracyclines, Macrolides, Metronidazole, Clindamycin, Nitrofurantoin, Fosfomycin and Chloramphenicol.

Answer 14

1-Aggressive broad coverage. In asplenic patients, treatment should include coverage of encapsulated organisms, particularly Streptococcus pneumoniae, that may cause rapidly life-threatening infection.

2-B-Lactams: Ranges from rash to anaphylaxis

Vancomycin: Nephrotoxicity (trough lvls>20ug/mL), red man syndrome.

Aminoglycosides: Nephrotoxicity (prolonged use), Ototoxicity.

Fluoroquinolones: QTc prolongation, tendinitis (elderly)

Rifampin: Hepatotoxicity (esp w other anti-TB agents), LFTs may be transiently elevated without symptoms. Orage discolouration of body fluids.

Tetracyclines: GI symptoms and photosensitivity

Macrolides: GI symptoms and QTc prolongation (Azithro)

Metronidazole: Peripheral Neuropathy

Clindamycin: Diarrhoea and pseudomembranous colitis

Nitrofurantoin: Pneumonitis and Peripheral neuropathy (in pts w renal failure)

Fosfomycin: GI symptoms

Chloramphenicol: Bone marrow suppression.

Question 15

1-What important questions to be asked in the history?

2-What are some reasons for failure of AB therapy?

Answer 15

1-Occupation and social exposures, sick contacts, animals, insects, water, sites of residence and past travel.

2-Antibacterial regimen that does not address causative organism, development of resistance during therapy, or the existence of a focus of infection at a site poorly penetrated by systemic therapy.

Question 16

1-What are the four types of anti-biotics classed as B-lactams?

2-What is their primary mechanism of action?

3-What is Penicillin G AKA BenPen active against?

Answer 16

1-Penicillins, cephalosporins, carbapenems, and monobactams (differing side-chains determine spectrum of activity)

2-B-lactams exert a bactericidal effect by inhibiting bacterial cell-wall synthesis.

3-Active against non B-lactamase-producing gram-positive and gram-negative bacteria, anaerobes, and some gram-negative cocci.

e.g. Bacterial endocarditis, Meningitis, Aspiration Pneumonia, Lung Abscess, CAP, Syphilis, susceptible strep infections.

Question 17

1-Which penicillins are anti-staphylococcal and have high potency against methicillin-susceptible Staphylococcus Aureus (MSSA)

2-What are aminopenicillins and what are their added coverage?

3-What are the anti-pseudomonal penicillins?

4-Why are β-lactam–β-lactamase inhibitor combinations needed and what are some examples?

Answer 17

1-Nafcillin, Oxacillin, Dicloxacillin, and Flucloxacillin

2-Ampicillin and Amoxicillin, provide added coverage beyond penicillin against gram-negative cocci e.g. Haemophilus Influenzae, some enterobacteriaceae incl E.Coli, Proteus mirabilis, Salmonella, and Shigella.

NB: IV Ampicillin is commonly used for Meningitis and endocarditis.

3-Ticarcillin and Piperacillin

4-Due to rising prevalence of β-lactamase-producing bacteria. Ampicillin-sulbactam, Amoxicillin-clavulanate, Ticarcillin-clavulanate, piperacillin-tazobactam, ceftolozane-tazobactam, ceftazidime-avibactam, and meropenem-vaborbactam.

NB: Avibactam and vaborbactam inhibit a broader spectrum of β-lactamases incl extended-spectrum B-lactamases (ESBLs)

Question 18

1-What are the generations of Cephalosporins and what ABs are in each?

2-What are the different uses for each generation?

3-Which third generation AB penetrates the CSF and which is the only third generation AB that covers for pseudomonas aeroginosa?

Answer 18

1-First generation: Cefazolin, Cephalexin

Second generation: Cefuroxime

Third generation: Cefotaxime, Ceftazidime, Ceftriaxone

Fourth generation: Cefepime

Fifth generation: Ceftaroline

2-First: Largely active against gram-positive bacteria, some activity against E. coli, P. mirabilis, and Klebsiella pneumoniae. Commonly used for MSSA and streptococci (e.g skin and soft tissue). Cefazolin is popular for surgical prophylaxis against skin organisms.

Second: Additional activity against H. influenzae and Moraxella catarrhalis. Used to treat CAP because of activity against S. pneumoniae, H. influenzae, and M. catarrhalis. Also used for mild-mod infections e.g acute otitis media and sinusitis.

Third: Greater potency against gram-ve bacilli, reduced potency against gram+ve cocci. Used for infections caused by Enterobacteriaceae. Ceftriaxone penetrates the CSF, can be used to treat meningitis caused by H. influenzae, N. meningitidis, and some strains of S. pneumoniae. Also late-stage Lyme disease, gonococcal infections, and streptococcal endocarditis.

Fourth: Broad-coverage agents with potent activity against both gram-ve bacilli, incl P. aeruginosa, and gram-positive cocci. Similar clinical applications to third generation. Can be used in bacteremia, febrile neutropenia, and intraabdominal and UTIs.

Fifth: Added activity against MRSA, which is resistant to all other β-lactams. Some gram-ve activity but does not include P. aeruginosa. Emerging data support Ceftaroline in more severe infections such as bacteremia.

3-Ceftriaxone penetrates the CSF and Ceftazadime in the only third generation cephalosporin with activity against Pseudomonas aeroginosa (lacks gram+ve cover).

Question 19

1-What ABs are in the Carbopenem category and what do they cover?

2-Are Carbapenems active against MRSA?

3-What does Ertapenem have poor activity against?

4-What is Imipenem specifically active against?

Answer 19

1-Imipenem, Meropenem, and Ertapenem. Most reliable coverage for strains containing ESBLs, broad activity against gram-positive cocci, gram-negative bacilli, and anaerobes. all are active against MSSA, Streptococcus species, and Enterobacteriaceae.

2-No, none are active against methicillin-resistant S. aureus (MRSA).

3- Ertapenem is the only carbapenem that has poor activity against P. aeruginosa and Acinetobacter.

4- Imipenem is active against penicillin-susceptible Enterococcus faecalis but not Enterococcus faecium

Question 20

1-What is a Monobactam and what is the coverage?

2-In what situation are these ABs commonly used?

Answer 20

1-Aztreonam is the sole monobactam. Its activity is limited to gram-ve bacteria incl P. aeruginosa and Enterobacteriaceae.

2-Principal use for aztreonam is as an alternative to penicillins, cephalosporins, or carbapenems in patients with a serious β-lactam allergy. NB: Aztreonam is structurally related to ceftazidime-use cautiously in individuals with a serious ceftazidime allergy.

Question 21

1-What are the most common adverse effects with the B-lactam drug class?

Answer 21

1-GI SE mainly diarrhoea, but hypersensitivity reactions constitute the most common adverse effect of β-lactams.

NB: Second-, third-, and fourth-generation cephalosporins and the carbapenems display very low cross-reactivity in patients with penicillin allergy. Aztreonam is the only β-lactam that has no cross-reactivity with the penicillin group.

NB: β-Lactams rarely cause serum sickness, Stevens-Johnson syndrome, nephropathy, hematologic reactions, and neurotoxicity. Neutropenia and interstitial nephritis appear to be related to high doses or prolonged use and generally resolve upon discontinuation.

Question 22

1-What is the most common Glycopeptide and what is it active against?

2-What are the important clinical uses for Vancomycin?

3-When is Vancomycin used PO?

4-What are the toxicity risks of Vancomycin and what are the target trough levels?

5-What is a serious skin reaction to Vancomycin and how is it managed?

6-What are the Lipoglycopeptides?

7-What are the common SE to Glycopeptides and Lipoglycopeptides?

Answer 22

1-Vancomycin is a Glycopeptide AB with activity against staphylococci (incl MRSA and coagulase-ve staphylococci), streptococci (incl S. pneumoniae), and enterococci. It is NOT active against gram-ve organisms.

2-Serious infections caused by MRSA, incl HA pneumonia, bacteremia, osteomyelitis, and endocarditis. It is also commonly used for skin and soft tissue infections.

3- Oral use is reserved for the treatment of Clostridium difficile infection.

NB: Vancomycin is also an alt for the rx of infections caused by MSSA in patients who cannot tolerate β-lactams

4-Targeting a vancomycin trough level of 15–20 μg/mL in MRSA infections in order to maintain an AUC/MIC ratio >400. Nephrotoxicity is the primary concern, esp with concomitant nephrotoxic agents e.g. Aminoglycosides. Adverse effects are reversible with discontinuation.

5-Red Man Syndrome is a common reaction that presents as a rapid onset of erythematous rash or pruritus on the head, face, neck and upper trunk. Caused by histamine release from basophils and mast cells and can be treated with diphenhydramine and slowing of the Vanc infusion.

6-Lipoglycopeptides are structurally similar to Vancomycin- Telavancin, dalbavancin, and oritavancin. Antibacterial activity against S. aureus (incl MRSA and some strains of vancomycin-intermediate S. aureus [VISA] and vancomycin-resistant S. aureus [VRSA]), streptococci, and enterococci.

7-Headache, gastrointestinal side effects, potential for QTc prolongation.

NB: Telavancin may interfere with certain coagulation tests (e.g., causing false elevations in prothrombin time).

Question 23

1-What is a Lipopeptide and what does it cover?

2-What are the main SE to Daptomycin?

Answer 23

1-Daptomycin is a lipopeptide antibiotic with activity against a broad range of gram+ve organisms. Active against staphylococci (incl MRSA and coagulase-negative staphylococci), streptococci, and enterococci.

NB: Daptomycin remains active against enterococci that are resistant to vancomycin.

2- Its main toxicity consists of elevation of creatine phosphokinase (CPK) levels and myopathy

Question 24

1-What are the common Aminoglycoside medications and what do they mainly treat against?

2-What is the reason behind the dosing interval of Aminoglycosides?

3-What synergistic effect do Aminoglycosides have on other ABs?

4-What bacteria are Aminoglycosides frequenty used to treat?

5-What toxicities are a concern for Aminoglycosides?

Answer 24

1- Gentamicin, tobramycin, and amikacin, although others, such as streptomycin, kanamycin, neomycin, and paromomycin, may be used in special circumstances.

2-Aminoglycosides have a significant dose-dependent postantibiotic effect; i.e., they have an antibacterial effect even after serum drug levels are undetectable. This forms the rationale behind extended-interval aminoglycoside dosing, in which a larger dose is given once daily rather than smaller doses multiple times daily.

3-Enhances activity of cell wall–active agents such as β-lactams or vancomycin against some gram-positive bacteria, incl staphylococci and enterococci. Synergistic because the effect of both agents provides a killing effect greater than either agent alone.

4-P. aeruginosa infection. Also, when used in combination with a cell wall–active agent, gentamicin and streptomycin are also important for the treatment of gram-positive bacterial endocarditis.

5-Nephrotoxicity-usually reversible, Ototoxicity-can be irreversible.

Question 25

1-What are the most common Macrolides and Ketolides and what is their MOA?

2-How does erythromycin differ to the other agents?

3-What are macrolides commonly used to treat?

4-What do macrolides specifically NOT cover?

5-What are the common SE to Macrolides?

Answer 25

1-Macrolides (azithromycin, clarithromycin, and erythromycin) and Ketolides (telithromycin) act to inhibit protein synthesis.

2-Azithromycin and Clarithromycin have better oral absorption and tolerability, as well as broader spectrum than erythromycin (older and less frequently used).

3- Upper and lower respiratory tract infections caused by S. pneumoniae, H. influenzae, M. catarrhalis, and atypical organisms (e.g., Chlamydia pneumoniae, Legionella pneumophila, and Mycoplasma pneumoniae); group A streptococcal pharyngitis in penicillin-allergic patients; and nontuberculous mycobacterial infections (e.g Mycobacterium marinum and chelonae) as well as treatment of M. avium-intracellulare infection in patients with HIV/AIDS and combo therapy for Helicobacter pylori infection and bartonellosis.

4-Enterobacteriaceae, Pseudomonas species, and Acinetobacter species are intrinsically resistant to macrolides.

5-Nausea, vomiting, diarrhea and abdo pain, prolongation of QTc interval, exacerbation of myasthenia gravis, and tinnitus.

NB: Erythromycin, clarithromycin, and telithromycin inhibit the CYP3A4 hepatic drug-metabolizing enzyme, which can result in increased lvls of benzodiazepines, statins, warfarin, cyclosporine, and tacrolimus.

Question 26

1-What is the class and MOA of Clindamycin?

2-What is it most commonly used for?

3-When is it used in combination?

4-What is the Clindamycin bioavailability and what are teh side effects?

Answer 26

1-Clindamycin is a lincosamide antibiotic and is bacteriostatic against some organisms and bactericidal against others.

2-Most often to treat bacterial infections caused by anaerobes (e.g., B. fragilis, Clostridium perfringens, Fusobacterium species, Prevotella melaninogenicus, and Peptostreptococcus species) and susceptible staphylococci and streptococci. For treatment of dental infections, anaerobic lung abscess, and skin/soft tissue infections.

3-Used together with bactericidal agents (penicillins or vancomycin) to inhibit new toxin synthesis in the treatment of streptococcal or staphylococcal toxic shock syndrome. NB: Also used for Toxoplasmosis.

4- Clindamycin has excellent oral bioavailability. AEs include nausea, vomiting, diarrhea, C. difficile–assoc diarrhea and pseudomembranous colitis, maculopapular rash, and (rarely) Stevens-Johnson syndrome.

Question 27

1-What are the common Tetracyclines and Glycylcyclines and what is their MOA?

2-What infections are they most commonly used to treat?

3-What are the main precautions with Tetracyclines?

Answer 27

1-Doxycycline, minocycline, and tetracycline and the glycylcyclines (tigecycline) inhibit protein synthesis and are bacteriostatic.

2-Used in the rx of skin/soft tissue infections caused by gram+ve cocci (incl MRSA), spirochetal infections (e.g Lyme disease, syphilis, leptospirosis), rickettsial infections (e.g., Rocky Mountain spotted fever), atypical pneumonia, STIs (e.g., Chlamydia trachomatis infection, lymphogranuloma venereum, and granuloma inguinale), infections with Nocardia and Actinomyces, brucellosis, tularemia, Whipple’s disease, and malaria.

3-Major AEs are nausea, vomiting, diarrhea, and photosensitivity. Tetracyclines have been associated with fetal bone-growth abnormalities and should be avoided during pregnancy and in the rx of children <8 years old.

Question 28

1-What are the two mechanisms of Trimethoprim-Sulfamethoxazole?

2-What is it active against and what are the most common clinical uses?

3-What is the SE profile and what are the interactions?

Answer 28

1-Two components that inhibit folate synthesis and produce antibacterial activity

2-Active against gram+ve bacteria such as staphylococci and streptococci. Also active against many gram-ve bacteria, incl H. influenzae, E. coli, P. mirabilis, Neisseria gonorrhoeae, and S. maltophilia. UTIs, skin/soft tissue infections, and respiratory tract infections are among the clinical uses.

NB: Not active against anaerobes or P. aeruginosa.

3- GI effects such as nausea, vomiting, and diarrhea. With prolonged use, leukopenia, thrombocytopenia, and granulocytopenia can develop. Nephrotoxicity, hyperkalemia, and hyponatremia, are more common at high doses. Interactions with other drugs incl warfarin, phenytoin, and methotrexate.

Question 29

1-What are the most common Fluoroquinolones and what are they active against?

2-What is a specific clinical example where Fluoroquinolones are useful?

3-What are the side-effects of Fluoroquinolones?

Answer 29

1-Fluoroquinolones incl norfloxacin, ciprofloxacin, levofloxacin, moxifloxacin. Ciprofloxacin and levofloxacin have the broadest spectrum of activity against gram-ve bacteria, including P. aeruginosa (similar to third-generation cephalosporins). Levofloxacin and moxifloxacin, have additional gram+ve activity incl against S. pneumoniae and some strains of MSSA.

NB: Strains of MRSA are commonly resistant to all fluoroquinolones

2- The penetration of fluoroquinolones into prostate tissue supports their use for bacterial prostatitis.

3-Generally well tolerated but can cause CNS stimulatory effects, incl seizures; peripheral neuropathy; glucose dysregulation; and tendinopathy assoc with Achilles tendon rupture, particularly in older patients, organ transplant recipients, and patients taking glucocorticoids. Also increased risk of aortic aneurysm and worsening of myasthenia gravis.

Question 30

1-What are the Rifamycins and what are they used to treat?

2-What are the most common SE?

Answer 30

1- Rifamycins include rifampin, rifabutin, and rifapentine. It is used in combination with other agents to reduce the likelihood of rifampin resistance. Used foremost in rx of mycobacterial infections—specifically, as a mainstay of combination therapy for M. tuberculosis infection or as a single agent in the rx of latent M. tuberculosis infection. Also used in the rx of nontuberculous mycobacterial infection. Used in combination regimens for the rx of staphylococcal infections, particularly prosthetic-valve endocarditis and bone infections with retained hardware. Part of combination therapy for brucellosis (with doxycycline) and leprosy.

NB: Rifampin has high oral bioavailability, esp when taken on an empty stomach.

2-Elevated aminotransferase levels (14%), rash (1–5%), and gastrointestinal events such as nausea, vomiting, and diarrhea (1–2%).

Question 31

1-What infection is Metronidazole effective in treating?

2-When and for what infections is it often the agent of choice?

3-What is Metronidazole MOA and bioavailability incl penetration into central structures?

4-What are the common SE?

5-What medications does metronidazole interact with?

Answer 31

1-Anaerobic bacterial infections, as well as protozoal (e.g. amebiasis, giardiasis, trichomoniasis)

2-Often used as part of combination therapy for polymicrobial abscesses in the lung, brain or abdomen

NB: Anaerobic infections e.g. Bacteroides, Fusobacterium, and Prevotella. Also alt rx for C.Difficile assoc diarrhoea.

3-Bacteriocidal against anaerobic bacteria. High oral bioavailability and tissue penetration including blood brain barrier (BBB).

4-Nausea, Diarrhoea and Metallic taste. Ingestion of alcohol may result in disulfiram-like reaction. More SE with L-T use.

5-Metronidazole has an effect on CYP2C9 drug metabolising enzyme, coadministration with Warfarin, Lithium and Phenytoin can result in decreased metabolism (higher blood levels/toxicity).

Question 32

1-What class is Linezolid in and what is it’s MOA?

2-What is the oral bioavailability of Linezolid?

3-What are the SE of Linezolid?

4-What are the medication interactions and what is the MOA behind this?

Answer 32

1-Linezolid is an Oxazolidinone, a bacteriostatic agent indicated for serious infections due to resistant gram-positive bacteria e.g. MRSA and VRE.

2-Excellent oral bioavailability.

3-With L-T use, myelosuppression and ocular and peripheral neuropathy.

4-Linezolid is a weak monoamine oxidase inhibitor, and has been assoc with serotonin syndrome with given with several serotonin reuptake inhibitors.

Question 33

1-What is the MOA of Nitrofurantoin and what is it active against?

2-What clinical infections is Nitrofurantoin primarily used to treat?

3-What are the common SE?

4-What are the drug and disease assoc interactions?

Answer 33

1-Nitrofurantoin damages DNA and is bactericidal. It is active against a range of gram+ve bacteria incl S. aureus, staphylococcus epidermis, staphylococcus saprophyticus, E. faecalis, streptococcus agalactiae etc some gram-ve incl E. coli, Enterobacter, Neisseria, Salmonella, and Shigella.

2-UTIs (particularly in pregnancy), may be used to prevent recurrent cystitis

3-Nausea, vomiting and diarrhoea. Rarely Pulmonary Fibrosis and drug induced hepatitis. NB: The frequency of SE increases with age.

4-Coadministration with magnesium decreases absorption. Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency are at increased risk of nitro induced haemolytic anaemia.

NB: Taking with food increases bioavailability and decreases SE.

Question 34

1-What AB class do Colistin and Polymyxin B belong to? What is their MOW and what do they act on?

2-What clinical infections are they used for?

3-What are the SE?

Answer 34

1-Polymyxins. Bactericidal, act by disrupting cell membrane activity and are active against nonenteric pathogens e.g. P.aeruginosa and A. baumannii (not burkholderia).

NB: Lack activity against gram+ve bacteria.

2-Mostly used for multi-drug resistant pathogens when they present in UTIs, HAP, and sepsis.

3-Dose dependent reversible nephrotoxicity. Reversible Neurotoxicity.

Question 35

1-What class does Quinupristin-Dalfopristin belong to, what is the MOA and what is it active against?

2-When is it most commonly clinically used?

3-What are the SE?

4-What metabolising enzyme does it inhibit?

Answer 35

1-Member of Streptogramin class. Bactericidal by inhibiting protein synthesis. Active against Staphlyococcis (incl MRSA), streptococci, and E.faecium (not E.faecalis). Also active against Corynebacterium and L.monocytogenes.

NB: Not active against gram-ve bacteria.

2-Vancomycin resistant E.faecium and other gram+ve bacterial infections e.g. UTIs, bone and joint infections, and bacteraemia.

3-Arthralgias and myalgias.

4-Inhibits CYP3A4 drug metabolsing enzyme. Which can result in increasing levels of drug and thus toxicity. (e.g. warfarin, ritonavir, cyclosporine, diazepam, verapamil).

Question 36

1-What class of ABs does Fosfomycin belong to, what is the dosing and how does it act?

2-What is it active against?

3-What are the AE?

Answer 36

1-Fosfomycin is a phosphonic acid AB that has greater activity in acid environments and is excreted in it’s active form in the urine. It is given in a single 3g dose that results in high urine levels for 48hrs.

2-Active against S.aureus, vancomycin-susceptible enterococci and VRE. Also a range of gram-ve organisms incl E.coli, Enterobacter, Serratia marcescens, P.aeruginosa, and K. pneumoniae. Also notably the majority of ESBL-producing Enterbacteriaceae.

3-Rarely reported, but include nausea and diarrhoea.

Question 37

1-When is Chloramphenicol indicated?

2-What are the limitations and SE?

3-What enzyme does it inhibit?

Answer 37

1-When other drugs are contraindicated or ineffective. Incl for meningitis caused by susceptible criteria such as N.meningitidis, H.influenzae, S.pneumoniae. It has also been used for rx of anthrax, brucellosis, Burkholderia, chlamydia, clostridial infections, erlichiosis, rickettsial and typhoid.

2-Chloramphenicol is limited by it’s potentially serious toxicities. SE include aplastic anaemia, myelosuppression, and gray baby syndrome.

3-Inhibits CYP3A4 drug-metabolising enzymes and thus increases levels of many classes of drugs.

Question 38

1-What is the most common presenting sign of liver abscess and what other symptoms might they have?

Answer 38

1-The most common presenting sign is fever. Patients may have RUQ pain, guarding, rebound tenderness or non-specific rigors/anorexia, wt loss, N+V.

NB: Only 50% of patients have any symptoms or signs to direct any attention to the liver.

Question 39

1-What are the most common serum fingings, if any for liver abscess?

Answer 39

1-Single most reliable lab finding is ALP (70% cases). Other LFTs may be normal, bilirubin and AST may be elevated (50%). Leucocytosis (70%) and Hypoalbuminaemia (30%).

Question 40

1-What is the best method for diagnosis of liver abscess?

Answer 40

1-USS, CT and MRI

*Liver abscess is sometimes suggested by CXR esp if elevation of R) hemidiaphragm

NB: Multilocular abscess are more common than solitary abscess

Question 41

1-What is the aetiology of Liver Abscess and what are the main organisms responsible?

Answer 41

1-Biliary tract (most common),

Portal system in assoc with intra-abdominal infection

Direct extension from intra-abdominal infection,

Penetrating wounds and postoperative complications

Hematogenous spread.

2-Klebsiella (most frequent), micro-aerophilic streptococci (mainly S. milleri) and

Candida in leukemia patients following neutropenia.

Question 42

1-What is the mainstay of treatment for Liver Abscess?

Answer 42

1-Depnding on the size, number and location of liver abscess, percutaneous drainage would be the primary management strategy. Empirical cover of the most likely organisms e.g. Ceftriaxone and Metronidazole would be sufficient starting point.

Question 43

1-What is a vegetation in infective endocarditis made up of?

2-What are the predispositions to endocarditis?

3-What body areas does infective endocarditis most commonly originate?

Answer 43

1-A mass of platelets, fibrin, microorganisms, and scant inflammatory cells.

2-Rheumatic heart disease (developing countries), illicit IVDU, degenerative valve disease, and intracardiac devices.

3-Oral cavity, skin and upper respiratory tract.

Question 44

1-What bacterial species cause the majority of Endocarditis cases?

2-In IVDU, what is the most common organism and what valve is ususally involved?

Answer 44

1-Viridans streptococci, staphylococci, and HACEK organisms (Haemophilus species, Aggregatibacter species, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae).

Health care–assoc NVE, most commonly caused by Staphylococcus aureus, coagulase-negative staphylococci (CoNS), and enterococci

2-Usually the tricuspid valve. Commonly caused by S. aureus, which in many cases is resistant to methicillin.

Question 45

1-What structures in the heart are most likely to be affected by bacteria and why?

2-What is nonbacterial thrombus endocarditis?

3-How does a valve vegetation form?

Answer 45

1-Heart valves via Endothelial injury (e.g. site of high velocity blood jets or low pressure side of cardiac lesion) allows infection of virulent organisms or development of platelet-fibrin thrombus.

NB:Undamaged epithelium is mostly resistant to infection

2-Development of a platelet–fibrin thrombus, which serves as a site of bacterial attachment during transient bacteremia.

3-Microorganisms induce a localized procoagulant state. Fibrin deposition, platelet aggregation and microorganism proliferation generate an infected vegetation. Organisms deep in vegetations are metabolically inactive (nongrowing) and relatively resistant to antimicrobials. Proliferating surface organisms are shed into the bloodstream continuously.

Question 46

1-What are the main clinical manifestations of endocarditis?

Answer 46

1-Embolization of vegetation fragments, leading to infection or infarction of remote tissues; hematogenous infection of sites during bacteremia

Question 47

1-What are the most common causative organisms for acute and sub-acute endocarditis?

2-What are the cardiac manifestations of endocarditis?

Answer 47

1-β-Hemolytic streptococci, S. aureus, and pneumococci typically result in an acute course. Subacute endocarditis is typically caused by viridans streptococci, enterococci, CoNS, and the HACEK group.

2-Regurgitant murmurs due to valvular damage and ruptured chordae, CHF as a consequence of valve dysfunction, perivalvular abscesses, varying degrees of heart block due to abscess, emboli to coronary artery (2%).

Question 48

1-What are the non-cardiac manifestations of endocarditis?

Answer 48

Clinical manifestations