Mechanism of action of common antibiotics

Betalactams (e.g. penicillins and cephalosporins): Inhibit cell wall synthesis.

Fluoroquinolones (e.g. ciprofloxacin and nalidixic acid): Bind to bacterial DNA gyrase and topoisomerase IV, interfering with bacterial DNA synthesis.

Tetracyclines: Bind to the bacterial 30S ribosome, inhibiting bacterial protein synthesis.
Aminoglycosides (e.g. gentamicin): Bind to 30S ribosome unit as well.

Macrolides (e.g. azithromycin): Reversibly bind to the 50S ribosomal subunit.

Sulfonamides (e.g. sulfamethoxazole): Inhibit steps in bacterial folic acid synthesis.

This stuff is high yield for Step 1.

GBS (Group B Strep) infections

Group B Streptococcus (GBS, Streptococcus agalactiae) is a common gram positive coccus that colonizes the vaginal and gastrointestinal tracts in 20-40% of healthy women. About half of GBS positive mothers will pass on the bacteria to their newborns but only 1% of these newborns will have a clinical infection. Transmission and clincal GBS disease is more common in premature infants and in women who have prolonged rupture of the membranes.

Neonatal group B streptococcal disease classically presents either as early or late sepsis. Early sepsis typically presents within 24 hours of birth but by definition can be evident up to seventh day of life. With early sepsis bacteremia and pneumonia are classic findings. Late sepsis on the other had can present up to 3 months postpartum and classically has bacteremia and meningitis.

Prevention: Term women with GBS positive cultures are treated with ampicillin intrapartum. Penicillin allergic patients can be treated with clindamycin or erythromycin.

GBS infection is otherwise rare in healthy individuals but the following conditions may predispose to an infection: Diabetes mellitus, malignancy, old age with bedridden state, cirrhosis, steroids, AIDS, renal failure, peripheral vascular disease. Common manifestations in these scenarios are urinary tract infection, pneumonia, and soft-tissue infection.

Pseudomembranous colitis (PMC)/Clostridium Difficile Infection

PMC is caused by Clostridium difficile which is a spore producing gram positive rod/bacillus. It's incidence is about 0.5% in hospitalized adults. PMC typically occurs in setting of altered gut flora due to antibiotics.

Common antibiotics impicated include: Clindamycin, Ciprofloxacin (and other fluoroquinolones), Cephalosporins and macrolides. Both Vancomycin and Metronidazole which are used in treatment of PMC can also cause PMC. Omeprazole(and other proton pump inhibitors) and chemotherapeutic drugs have also been shown to increase risk for PMC.

Treatment is typically done with oral metronidazole (Flagyl) or oral vancomycin. Of the two metronidazole is usually preferred because it is relatively inexpensive and to reduce the risk of developing vancomycin resistant enterococci (VRE) organisms.

Hidradenitis Suppurativa

Hidradenitis suppurativa is a chronic inflammatory condition characterized by painful lesions in various parts of the body with sweat glands. Typical sites are either groin or axillara (arm pit). The primary gland involved are the apocrine variety of sweat glands (those that produce the characteristic odor). It usually results from blockage of the duct of the gland which leads to distension and inflammation of the surrounding tissues.


Surgical drainage may be needed to relieve pain or if there is bacterial super-infection (evident by redness, exquisite tenderness, pus drainage or fevers). Antibiotics are usually indicated in that case to treat the surrounding cellulitis.

Salmonella infection in humans

Salmonella infections occur mainly via ingestion of contaminated food. Ingested bacteria are usually killed by the acid in the stomach but when they do survive they can cause enteritis. Certain conditions that reduce the acidity in the stomach predispose to infection (e.g.infants, H2 pr Proton pump inhibitor use and pernicious anemia). It has been predicted that about one million organisms need to be ingested to cause infection.

Infection manifests with fever, loose stools, vomiting, dehydration and cramping pain.

Treatment 

Salmonella enteritis is usually self-limiting and does not need antibiotic therapy. Fluid management and symptoms control are the mainstay of the treatment.

However, antibiotics may be indicated in the following high risk groups:

Infants especially in the first 3 months of life
Elderly
Immunocompromised hosts
Individuals with prosthetic heart valves or joints

Salmonella is sensitive to a variety of antibiotics including fluoroquinolones(ciprofloxacin, ofloxacin, levofloxacin), azithromycin, trimethoprim/sulfamethoxazole(Bactrim/Septran) or amoxicillin.

Carrier state

Carrier state is defined as having positive stool cultures for >12 months. It can occur in 1 in about every 200 patients with salmonella enteritis. The bacteria resides in the biliary tree. Chronic antibiotic therapy (Ampicillin) or surgery is needed.

Pyogenic Liver(hepatic) Abscess

Pyogenic liver abscesses are usually secondary to peritonitis due to that subsequently spread to liver via the portal circulation or bile ducts. Other common form is as a result of hematogenous seeding in the setting of sepsis.

Clinical manifestations: fever, abdominal pain, nausea, vomiting, anorexia, weight loss and malaise.

Diagnosis of pyogenic liver abscess is confirmed by imaging (ultrasound r CT) followed by aspiration and culture of the abscess material. Most pyogenic liver abscesses are polymicrobial. Serology is useful in distinguishing pyogenic abscess from an amebic abscess.

Indications for drainage(less than 5cm usually aspiration is sufficient, greater than 5cm usually need in dwelling catheter):

- Loculated abscesses

- Abscesses with viscous contents obstructing drainage catheter

- Underlying disease requiring primary surgical management

- Inadequate response to percutaneous drainage within seven days
- Multiple abscesses (depends on number, position, and size)

Antibiotics:
A total of 4-6 weeks of therapy is needed.


Options for empiric gram-negative and anaerobic coverage include:

1) Penicillin derivatives: Ampicillin-sulbactam, Piperacillin/tazobactam or Ticarcillin-clavulanate
2) Cephalosporins: Ceftriaxone with metronidazole
3) Fluoroquinolone: Ciprofloxacin or Levofloxacin with metronidazole
4) Carbapenems: Imipenem, Meropenem or Ertapenem

Herpes labialis

Image from CDC public health image library

Herpes labialis or 'cold sore' is caused by Herpes simplex virus (HSV) type 1 which is a double-stranded, enveloped, DNA virus. Diagnosis is clinical. Treatment is symptomatic. Topical acyclovir may be helpful in recurrent cases.

Vibrio cholera

This organism can not survive in acidic pH. Hence any condition that causes decrease stomach acidity will cause it to proliferate.

Botulism

Botulism is caused by a gram positive rod Clostridium botulinum. The toxin released by this bacteria binds irreversibly to the presynaptic membranes of peripheral neuromuscular and autonomic nerve junctions. This binding inhibits acetylcholine release, causing weakness and flaccid paralysis. The paralysis persists until the nerve endings regenerate.

The 3 types of botulism are as follows:

Infant botulism is caused by ingested spores of the bacteria which germinate in the gut releasing toxin inside the body.

Wound botulism results from contamination of a wound with toxin-producing clostridia.

Foodborne botulism occurs after consumption of contaminated food for e.g. canned vegetables.

Key points for USMLE:
-The binding of toxin is irreversible
-Infant botulism is associated with consumption of honey

Differential diagnosis of botulism:

* Guillain-Barré syndrome
* Myasthenia gravis
* Lambert-Eaton myastheic syndrome
* Polio
* Tick paralysis
* Stroke
* Diphtheric paralysis
* Congenital neuropathy or myopathy
* Snake bite (Cobra)

Legionnaire’s Disease

Legionnaire’s Disease – caused by Legionella Pneumonia causes disease in smokers, with diarrhea, headache and confusion.

Clinical manifestations of Aspergillus infection of the lungs(Pulmonary aspergillosis)

There are four common manifestations of pulmonary aspergillosis namely - Allergic Broncho Pulmonary Aspergillosis (ABPA), Chronic Necrotizing Pulmonary Aspergillosis(CNPA), aspergilloma ('Fungal ball') and invasive aspergillosis.

 

1) ABPA - is almost exclusively seen in asthmatics or cystic fibrosis patients. It is basically an allergic reaction to aspergillus that is colonized in the airways. Patients have fever and respiratory symptoms (cough, hemoptysis, wheezing).

2) Aspergilloma -  is seen in immunocompromised patients. or in lungs with pre-existing cavities.  Aspergillomas are often silent or cause fever and respiratory symptoms similar to ABPA.

 

3) CNPA - Occurs in individuals with underlying disease, such as severe chronic obstructive pulmonary disease (COPD) and prolonged antibiotic therapy. They present with symptoms  such as fever, cough, night sweats, and weight loss.

 

4) Invasive aspergillosis - occurs in patients with immunosuppression or ANC (Absoulute neutorphil count) and in patients post transplantation. These patients are usually sick and need urgent parenteral treatment.

Myocarditis classification

Myocarditis is inflammation of myocardium. It is usually viral and Cocksackie B is the commonest virus isolated. Myocarditis can be classified into the following 3 types based on pathologic findings per the Dallas Criteria (1987):

Active myocarditis - Characterized by abundant inflammatory cells and myocardial necrosis (subclassified into ongoing, resolving, or resolved myocarditis.)

Borderline myocarditis - Characterized by an inflammatory response that is too sparse for this type to be labeled as active myocarditis; degeneration of myocytes not demonstrated with light microscopy (subclassified into ongoing, resolving, or resolved myocarditis.)

Nonmyocarditis

Influenza - antigenic drift and shift explained.

Influenza viruses are constantly evolving by reassortment of their genetic material. Mutations cause minute changes in the hemagglutinin and neuraminidase antigens on the surface of the virus. This change is gradual(increasing with each division cycle) and is called antigenic drift. Since the strains produced by drift are somewhat similar to the older strains, some people are still immune and some others will be partly immune (and get a milder illness).

It is due to this antigenic drift that a new vaccine has to be manufactured and reimmunization is recommended each year.

In contrast, antigenic shift occurs when influenza viruses reassort. The virus acquires completely new antigens—for example by reassortment between avian strains and human strains. If a human influenza virus is produced that has entirely new antigens, everybody will be susceptible, and the novel influenza will spread uncontrollably, causing a pandemic.

Lyme Disease

Caused by B burgdorferi is a spirochete. It is transmitted from host to host by the Ixodes, or deer tick. 

Treatment:

Tick bite: Single dose of 200 mg of doxycycline within 72 hours of removing a tick can prevent the development of Lyme disease. This still should be limited to patients who have had possible tick exposure in endemic areas.

Skin manifestations: Institute an oral regimen for 30 days.

Arthritis: Institute an oral regimen for 30 days. * Re-treat for 30 days with oral regimen or intravenous ceftriaxone for 14-30 days if the first oral course is unsuccessful.

Neuroborreliosis

• Facial palsies: Institute an oral regimen for 30 days. Although facial palsies may resolve without treatment, antibiotic therapy may prevent further sequelae.
• Paresthesias/radiculopathy: Institute intravenous therapy for 14 days. Oral doxycycline for 30 days may be as good as intravenous ceftriaxone for neuroborreliosis.
• Encephalitis/encephalopathy: Institute intravenous therapy for 28 days.

Kawasaki Disease

Fever persisting at least five days*: the fever is generally high and spiking (often to 40°C [104°F] or higher).

Presence of at least four of the following features:

Changes in extremities: including redness, swelling and, sometimes, induration of the hands and feet. Desquamation of the fingers and toes occurs (Usually 2-3 weeks after fever). Beau's lines (white lines across the fingernails) may appear after 2-3 months.

Rash: may have several forms, including urticarial exanthem. Bullae and vesicles are not seen. The rash usually appears within five days after the onset of fever.

Bilateral conjunctival injection: the bulbar conjunctivae, rather than the palpebral or tarsal conjunctivae, are red. Typically, the limbic region is spared. It is not associated with an exudate and is usually painless.

Changes in the lips and oral cavity:including strawberry tongue, redness and cracking of the lips, and erythema of the oropharyngeal mucosa. No ulcers usually.

 

Cervical lymphadenopathy: the lymphadenopathy is usually unilateral, with firm and slightly tender nodes. Cervical lymphadenopathy is the least common feature found in the United States. It is a much common finding in Asia.

Malaria prophylaxis

The drug of choice for prophylaxis for a patient travelling to malaria endemic region is?

A) Choloroquin

B) Dapsone

C) Sulfapyridine

D) Doxycycline

E) Mefloquine

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Mefloquine

( Also remember the most important toxicity of Mefloquine is Hepatic. Travel related questions appear frequently on the USMLE.)

 

Quiz

6-year-old boy developed disseminated red papules, vesicles and crusted vesicles after 3 days of fever.

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Diagnosis: Chicken Pox (Varicella). Note the polymorphic rash with lesions in different stages of development

5th disease vs. 6th disease

5th disease is also called erythema infectiosum. It is caused by Human Parvo Virus and has slapped cheek appearance.

 

6th disease is also called roseola infantum. It is caused by Human Herpes Virus 6 and characteristically the rash appears after fever disappears.

Jarisch-Herxheimer reaction

Jarisch-Herxheimer Reaction occurs when large quantities of toxins are released into the body as bacteria (typically Spirochetal bacteria) die, due to antibiotic treatment. It is important to distinguish this reaction from Penicillin allergy. In the USMLE one is typically given a case with allergic symptoms following treatment of syphilis with Penicillin. There are usually other clues in the question about the diagnosis. Dont blindly mark Jarisch Herxheimer as the answer.

Quiz

Why should children with Juvenile Rheumatoid Arthritis be vaccinated against Varicella?

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? Reye's Syndrome: Microvesicular fatty liver change & encephalopathy 2° to Aspirin ingestion in children following viral illness, especially VZV.