Infection, Pharmacology & VTE MCQs

Based on the description of the infection and the history of close contact, the clinical scenario is most consistent with community-acquired MRSA (CA-MRSA). It is important to distinguish CA-MRSA and hospital-acquired MRSA (HA-MRSA) as the two display different sensitivities to antibiotics. Antibiotic selection is based on sensitivity and severity of infection. Because this infection is superficial and withoutany signs of systemic illness, an oral antibiotic regimen is appropriate. When culture results reveal resistance to erythromycin, then a D-zone test should be performed to check for inducible clindamycin resistance. The D-zone test is performed by plating the sample on an agar and placing antibiotic disks made of clindamycin and erythromycin on the agar. A zone of inhibition in the shape of the letter D is seen with an inducible strain. If the D-zone test is positive, then clindamycin should not be used because the strain of MRSA can become resistant to the treatment. Therefore, because of the positive D-zone test, the antibiotic should be changed to oral doxycycline. IV antibiotics are not indicated for this infection. Oral rifampin should never be used as a single agent as resistance rapidly develops.

The patient has a late infection of at least 4 weeks symptomatic duration that most likely is hematogenous in etiology. This infection is not an acute hematogenous infection that can successfully be treated with irrigation and debridement. Retention of the implants with debridement and irrigation alone has been associated with a poor prognosis. In one study of 50 infections attributable to MRSA or methicillin-resistant Staphylococcus epidermidis organisms treated with a two-stage protocol, the failure rate was 21%.

Activation of antithrombin (AT) III is the mechanism of action of heparin. Heparin works by binding to and enhancing the ability of antithrombin III to inhibit factors IIa, III, and Xa. It is metabolized by the liver. The risks associated with its use include bleeding and heparin-induced thrombocytopenia (HIT). The reversal agent is protamine sulfate.

DISCUSSION: Demographic factors are associated with increased risk for MRSA colonization, so it is important to identify vulnerable patients. Female gender and advanced age reduce the risk for colonization, whereas African American race increases this risk. Urban environments do not influence MRSA colonization.

Dabigatran (Pradaxa) is a direct thrombin inhibitor that is approved for stroke prevention in atrial fibrillation. It is not a factor Xa inhibitor. Rivaroxaban and Apixaban are factor Xa inhibitors.

DISCUSSION: Patients who have skin and soft-tissue infections caused by CA-MRSA often describe the lesion as a spider bite. The cytotoxin Panton-Valentine leukocidin that is produced by many strains of CA-MRSA causes tissue necrosis, resulting in rapid development of an abscess and the appearance of a spider bite. Patients with psoriasis have thick, red skin with flaky, silver-white patches. Tinea corporis is a general term for a cutaneous fungal infection. The lesion appears as a well-demarcated erythematous plaque with a raised border and central hypopigmentation, giving it a ring-like appearance. Primary infection with herpes simplex virus can produce constitutional symptoms with burning, tingling, or stinging at the site. Grouped vesicles with clear fluid 1 to 2 mm in size form on an erythematous base and then rupture, leaving moist ulcers or crusted plaques.

The most likely diagnosis is chronic multifocal osteomyelitis. This is a culture-negative polyostotic disease that is most commonly found in young people. The treatment of choice is anti-inflammatory drugs. The pathology does not suggest eosinophilic granuloma. Antiviral therapy, broad-spectrum antibiotics, and surgical resection are not indicated for this disease.

DISCUSSION: Risk factors for sternoclavicular septic arthritis include IV drug abuse, diabetes, and HIV. According to the reference by Ross et al, Staphylococcus aureus accounts for 49% of infections. SC joint arthritis accounts for 1% of septic arthritis in the general population but 17% in the IV drug abuse population. Symptoms include spontaneous swelling with the appearance of joint subluxation and localized pain. These patients are not uncommonly afebrile.

Antifungals such as amphotericin and nystatin bind to sterols in the cell membrane and disrupt its integrity, allowing diffusion of macromolecules and causing cell death. Sulfonamides and trimethopim mimic the metabolite substrate and block synthesis of metabolites such as folic acid. Rifampin inhibits bacterial RNA polymerase, blocking synthesis of RNA. Tetracycline, chloramphenicol, and clindamycin bind to ribosomes and block bacterial growth by inhibiting protein synthesis.

DISCUSSION: This patient has cellulitis, which is typically caused by group A Streptococcus or Staphylococcus. The patient’s lack of improvement with first-line antibiotics is concerning for methicillin-resistant Staphylococcus aureus (MRSA) infection. MRSA cellulitis is becoming more prevalent in young athletes, and a high index of suspicion is required to provide appropriate intervention during this aggressive disease process. The diagnosis is typically made clinically without the use of cultures. Oral trimethoprim-sulfamethoxazole (a sulfonamide-class drug) double strength twice daily for 10 to 14 days or doxycycline (a tetracycline-class drug) 100 mg twice daily for 10 to 14 days are recommended for first-line treatment of suspected MRSA cellulitis. There is no indication to proceed with irrigation and debridement; however, if the patient develops a soft-tissue abscess or the underlying joint becomes involved, this would be an appropriate intervention. Switching the athlete to an IV cephalosporin (cefazolin) is not likely to be effective against the presumed resistant bacteria. Ciprofloxacin (a fluoroquinolone-class drug) is effective against many bacteria, but not MRSA. The current recommendation for wrestlers with cellulitis is that return to competition be allowed after 72 hours of antibiotic treatment if there has been no extension of the cellulitis for 48 hours, the lesion can be covered, and there is no drainage from the lesion. The other responses are not current recommendations for return to competition.

DISCUSSION: The initial signs and symptoms of acute hematogenous osteomyelitis vary widely but usually include fever, bone pain, and impaired use of the involved extremity. In lower extremity infections, the child may limp or refuse to walk. Examination often reveals bone tenderness. In more advanced cases, erythema, warmth, and swelling may be present. The WBC and neutrophil counts are not always elevated, but the erythrocyte sedimentation rate will be abnormal in more than 90% of patients. When the infection is diagnosed early, before a subperiosteal abscess has formed, antibiotics alone may be adequate to treat the infection. This patient has a more advanced infection, however, with the MRI scan revealing a subperiosteal abscess that was confirmed by aspiration. When an abscess is present, surgical drainage is generally indicated to remove devitalized tissue and to enhance the efficacy of the antibiotics. Further studies, such as bone or indium scans, are not necessary and will delay definitive treatment.

DISCUSSION: In the 2004 ACCP guidelines, there were three prophylactic regimens that received a grade 1A favorable recommendation. These included low-molecular-weight heparin, warfarin, or fondaparinux, as long as they are used for at least 10 days. If warfarin is used, the target INR should be 2.0 to 3.0, according to the guidelines. Pneumatic compression sleeves have gained popularity in the orthopaedic community but have not received a grade 1A rating from the ACCP at this time. Use of aspirin by itself is discouraged by the ACCP. REFERENCE: Geerts WH, Pineo GF, Heit JA, et al: Prevention of venous thromboembolism: The seventh ACCP Conference on antithrombotic and thrombolytic therapy. Chest 2004;126:338S-400S.

The patient has diastrophic dysplasia. Affected individuals have rhizomelic short stature, cauliflower ears, severe joint contractures (especially knees and hips), hitchhiker’s thumb, and a cleft palate. The most common foot abnormality is a rigid equinovarus deformity. Surgical results are poorer than those for idiopathic clubfeet and often require bony procedures or talectomy.

PVL is a cytotoxin that defines CA-MRSA and is not typical of hospital-acquired MRSA. PVL has the ability to lyse white blood cells and cause tissue necrosis, allowing for rapid progression of abscess formation. Beta-lactamase is an enzyme that breaks the beta-lactam bond of penicillin and is present in most strains of Staphylococcus aureus today. Synthetic penicillins such as methicillin are resistant to the effects of beta-lactamase. MRSA and CA-MRSA carry the mecA gene, which encodes a penicillin-binding protein with a very low affinity for beta-lactam antibiotics, resulting in methicillin resistance. SCCmec mobile genetic units carry the mecA gene with additional genetic elements that together yield the multidrug-resistant strains found in healthcare environments. SCCmec type IV is specific to CA-MRSA and lacks these additional genetic elements, resulting in less multidrug resistance.

Three basic mechanisms of antibiotic resistance have been identified: avoidance, decreased susceptibility, and inactivation. Biofilm formation is a classic example of avoidance, whereby the biofilm creates a physical barrier to the antibiotic. Bacteria can decrease their susceptibility to antibiotics by mutating the antibiotic target or generating a mechanism to inactivate the antibiotic. Biofilm formation develops when a sufficient mass of bacteria forms on a surface. The cell-to-cell signaling becomes sufficient to activate transcription of genes needed for biofilm formation in a processknown as quorum sensing. Once the bacteria produce a mature biofilm, they enter a greatly reduced or stationary phase of growth. Lastly, high-shear environments seem to stimulate biofilm production.

DISCUSSION: The radiograph reveals severe intestinal dilatation, which has occurred as the result of acute colonic pseudo-obstruction and is associated with excessive narcotic administration following total joint arthroplasty. Anesthetic type, antibiotic administration, and warfarin have not been associated with this obstruction. Electrolyte imbalances such as hypokalemia have been associated with postsurgical acute colonic pseudo-obstruction.

Corticosteroids prevent the formation of the pre-inflammatory mediator arachidonic acid from cell membrane phospholipids by inhibiting phospholipase A2. This inhibition prevents the earliest step in the inflammatory cascade. Arachidonic acid proceeds through the lipoxygenase pathway to produce leukotrienes, responsible for autocrine and paracrine signaling, or through the cyclooxygenase pathway (either COX-1 or COX-2) to produce prostaglandins. Thromboxane A2, present in platelets, activates phospholipase C which causes cellular effects resulting in platelet aggregation. Prostacyclin and thromboxane A2 work as antagonists. Prostacyclin is released from endothelial cells, inhibiting platelet aggregation and causing vasodilation.

TNFα has been implicated in the pathogenesis of many chronic inflammatory diseases. Selective blockade with agents such as etanercept decreases the activation of mesenchymal cells, thereby reducing pannus formation, cartilage destruction, and osteoclastic bone resorption. IL-1 production in response to inflammatory stimulus contributes to the rapid loss of proteoglycans, leading to cartilage destruction and osteoclastic bone resorption. Recombinant forms of IL-1 antagonists such as the drug anakinra effectively block IL-1 by competitively binding to the IL-1 type I receptor. Nonsteroidal anti-inflammatory drugs inhibit the enzymes COX-1 and COX-2, which are necessary for the production of prostaglandins. Abatacept is a selective costimulation modulator that inhibits T lymphocyte activation implicated in pathogenesis of juvenile idiopathic arthritis. Methotrexate is an effective agent in the treatment of rheumatoid arthritis. The mechanism of action of this drug has not been fully elucidated. Proposed actions include decreasing cytokine production through promotion of adenosine release and inhibition of transmethylation reactions that otherwise result in accumulation of toxic compounds (spermine and spermidine).

DISCUSSION: MRI findings of acute osteomyelitis include a decrease in the normally high signal intensity of bone marrow on T1-weighted imaging; however, a postgadolinium T1-weighted image with fat suppression will show osteomyelitis as a bright marrow signal compared to the surrounding fat. Osteomyelitis is also brighter than normal fat on T2-weighted imaging. There is no rim-enhancing lesion suggesting an abscess, although myositis is seen in the obturator internus and short external rotators. The clinical scenario and imaging studies do not support the diagnosis of septic hip, eosinophilic granuloma, or pelvic fracture.

Demographic factors are associated with increased risk for MRSA colonization, so it is important to identify vulnerable patients. Female gender and advanced age reduce the risk for colonization, whereas African American race increases this risk. Urban environments do not influence MRSA colonization.