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Mayo Clin Proc. 2010 February; 85(2): 172–175.
PMCID: PMC2813826

Clinical Pearls in Infectious Diseases

At the 2001 annual conference of the American College of Physicians, a new teaching format to aid physician learning, Clinical Pearls, was introduced. Clinical Pearls is designed with the 3 qualities of physician-learners in mind. First, we physicians enjoy learning from cases. Second, we like concise, practical points that we can use in our practice. Finally, we take pleasure in problem solving.

In the Clinical Pearls format, speakers present a number of short cases in their specialty to a general internal medicine audience. Each case is followed by a multiple-choice question answered live by attendees using an audience response system. The answer distribution is shown to attendees. The correct answer is then displayed and the speaker discusses teaching points, clarifying why one answer is most appropriate. Each case presentation ends with a Clinical Pearl, defined as a practical teaching point that is supported by the literature but generally not well known to most internists.

Clinical Pearls is currently one of the most popular sessions at the American College of Physicians meeting. As a service to its readers, Mayo Clinic Proceedings has invited a selected number of these Clinical Pearl presentations to be published in our Concise Reviews for Clinicians section. “Clinical Pearls in Infectious Diseases” is one of them.

CASE 1

A 22-year-old college sprinter has been experiencing symptoms of facial pressure, nonproductive cough, and purulent rhinorrhea for 8 days. She has a history of seasonal allergic rhinitis and has been taking loratadine without relief. She has an important track meet in 3 days. Her examination shows mild nasal erythema, mild tenderness over her left maxilla, but no pharyngeal purulence.

Question

Which one of the following would be the best treatment for this patient?

  1. Budesonide, 200-μg nasal spray once daily for 10 days
  2. Amoxicillin (500 mg 3 times daily for 10 days) plus budesonide (200 μg nasal spray once daily for 10 days)
  3. Amoxicillin-clavulanate, 875 mg orally for 10 days
  4. Nasopharyngeal humidification and ibuprofen for pain
  5. Levofloxacin, 750 mg/d for 5 days

Discussion

This college student presents with a slowly resolving upper respiratory tract infection with purulent rhinorrhea. Although she has been ill for 8 days and has some mild facial tenderness, she has no purulent pharyngeal exudate. In the United States, 80% of patients would receive a course of antibiotics1; however, several recent studies have shown that this practice of overprescribing antibiotics needs to change. A recent trial of patients randomized to a 7-day course of amoxicillin, amoxicillin plus budesonide, budesonide alone, or placebo showed no difference in the proportion of patients with symptomatic improvement.2 A review of individual patient data from a large meta-analysis of 2547 adults from 9 trials of antimicrobial agents for acute rhinosinusitis found that 15 patients needed to be treated to cure 1 patient even if symptoms lasted beyond 7 days.3 A large number of these patients developed adverse effects from the antibiotic treatment.

In the patient described in this case, a possible adverse effect would be Achilles tendon rupture, associated with fluoroquinolone use.4 Therefore, symptomatic treatment with nasopharyngeal humidification and ibuprofen for pain would be the most appropriate management choice.

Clinical Pearl

Antibiotics are not indicated in most cases of acute rhinosinusitis, regardless of whether symptoms last longer than 7 days.

CASE 2

A 35-year-old emergency department physician presents to your clinic with a 3-day history of cough, right-sided pleuritic chest pain, and fever. He is a nonsmoker and has no allergies. His vital signs are as follows: respiratory rate, 18 breaths/min; heart rate, 82 beats/min; and oxygen saturation by pulse oximetry, 94% while breathing room air. Chest radiography shows a dense right lower lobe consolidative infiltrate. A sputum culture done at his hospital workplace on the day his symptoms began yielded the following information on Streptococcus pneumoniae susceptibility (minimum inhibitory concentration [MIC]): penicillin, 1 μg/mL; ceftriaxone, <0.5 μg/mL; vancomycin, 0.5 μg/mL; erythromycin, >1 μg/mL; and levofloxacin, <0.5 μg/mL.

Question

Which one of the following antibiotics would be the best choice for treating this patient's infection?

  1. Meropenem, 1 g intravenously every 8 hours
  2. Azithromycin, 500 mg orally once daily
  3. Amoxicillin, 1000 mg orally 3 times daily
  4. Ceftriaxone, 1 g/d intravenously
  5. Trimethoprim-sulfamethoxazole, 1 double-strength tablet twice daily

Discussion

This patient has a right lower lobe pneumococcal pneumonia, the severity of which does not warrant hospitalization or the initiation of parenteral antibiotics. The MIC for penicillin is 1 μg/mL. Before 2008, this pneumococcal isolate would have been considered resistant to penicillin because the MIC was greater than 0.06. However, several studies have shown that these susceptibility break points do not correspond to treatment outcomes in patients with pneumonia or otitis media and were principally designed to ensure treatment success in S pneumoniae meningitis. Thus, the break points for S pneumoniae susceptibility were changed, and reporting should be specific to the clinical syndrome.5 Respiratory tract isolates with an MIC of 2 μg/mL or less should be considered susceptible to penicillin.

In this patient, an oral β-lactam such as amoxicillin would suffice for treatment. Meropenem is a broad-spectrum carbapenem, the use of which should be reserved for multiply resistant or polymicrobial infections, not community-acquired pneumonia. The isolate is macrolide resistant.

Clinical Pearl

Penicillin susceptibility break points for S pneumoniae differ depending on the clinical scenario.

CASE 3

A 33-year-old obese man with a history of recurrent skin abscesses due to methicillin-resistant Staphylococcus aureus (MRSA) presents to the emergency department with a productive cough, pleuritic chest pain, and dyspnea. One week ago he had influenza. Chest radiography shows multilobar infiltrates and early cavitation. A sputum Gram stain shows numerous gram-positive cocci in clusters.

The sputum culture grows 3+ S aureus, which has an MIC of less than 2 to oxacillin, 2 to vancomycin, and greater than 4 to clindamycin and which are susceptible to daptomycin, linezolid, and quinupristin/dalfopristin.

Question

Which one of the following antimicrobial regimens would be the best treatment for this patient's infection?

  1. Daptomycin, 6 mg/kg intravenously once daily
  2. Linezolid, 600 mg intravenously twice daily
  3. Vancomycin, 1 g intravenously twice daily
  4. Ceftriaxone (1 g/d intravenously) plus azithromycin (500 mg/d intravenously)
  5. Vancomycin (15-20 mg/kg intravenously twice daily) to achieve a trough concentration of 10 to 15 μg/mL plus clindamycin (600 mg intravenously every 8 hours)

Discussion

This patient has postinfluenzal cavitary pneumonia due to MRSA. Daptomycin is not an effective treatment for pneumonia due to its interaction with lung surfactant. The standard 1-g, twice-daily regimen of vancomycin would not achieve high enough concentrations to treat this severe MRSA infection. Currently recommended guidelines suggest achieving a trough vancomycin level of at least 15 to 20 μg/mL for serious infections, especially with a vancomycin MIC of 2.6 Ceftriaxone and azithromycin both lack activity against MRSA. The agent of choice is linezolid, which has been shown to be effective in MRSA pneumonia. Additionally, recent studies of postinfluenzal pneumonia in mice suggest that agents that inhibit the impact of inflammatory cytokines, particularly protein synthesis inhibitors (eg, clindamycin, azithromycin), may improve survival.7 Linezolid is also a protein synthesis inhibitor.

Clinical Pearl

In MRSA pneumonia with an elevated vancomycin MIC of 2, use either linezolid or doses of vancomycin that achieve trough concentrations of 15 to 20 μg/mL.

CASE 4

An 86-year-old woman with peripheral vascular disease, diabetes, and gastroesophageal reflux is admitted with fever, leukocytosis, and gangrenous ulcerations of her left ankle and foot. Treatment with vancomycin, levofloxacin, and clindamycin is initiated. On her third hospital day, she undergoes an above-the-knee amputation of her left leg. She improves and returns to a nursing home for rehabilitation. On her second day at the nursing home, she develops lower abdominal pain, 8 loose stools per day, and a leukocyte count of 18.0 × 109/L. She returns to the emergency department and a Clostridium difficile toxin test is performed, with positive findings.

Question

Which one of the following statements is true regarding this patient's C difficile infection?

  1. Vancomycin would be less effective than metronidazole for severe disease
  2. A relapse of disease would most likely be due to antibiotic resistance
  3. Treatment with vancomycin places the patient at greater risk of vancomycin-resistant enterococcal colonization than metronidazole treatment
  4. A single recurrence of infection increases her likelihood of further relapses
  5. A stool sample should be obtained and tested for C difficile toxin at the end of treatment to document cure before she returns to the nursing home

Discussion

C difficile is the most common infectious diarrhea in hospitalized patients. A recent prevalence survey conducted by the Association for Professionals in Infection Control and Epidemiology found that 13 of every 1000 inpatients in US hospitals had a C difficile infection. Persons older than 65 years had an even higher rate (19 per 1000 inpatients) of C difficile infection and a 4-fold increased mortality rate.8

This patient received both clindamycin and levofloxacin, 2 agents commonly associated with this complication. Patients who have 1 episode are predisposed to recurrences and those with 2 or more episodes are at highest risk of multiple relapses. Most relapses are due not to antibiotic resistance but rather to reinfection or germination of spores. Several recent studies suggest that oral vancomycin is more effective than metronidazole for treatment of severe C difficile disease.9 Vancomycin-resistant enterococcal colonization is often seen in similar patient populations who have received broad-spectrum antibiotics; however, no differences in vancomycin-resistant enterococcal colonization were observed in patients receiving vancomycin vs metronidazole for treatment of C difficile infection.10 Because stool toxin assays remain positive during and after successful treatment, follow-up stool toxin assays for test of cure should be avoided.11

Clinical Pearl

C difficile toxin should not be rechecked as a test of cure.

CASE 5

A 28-year-old woman with a history of recurrent Escherichia coli urinary tract infections while taking nightly cotrimoxazole presents with her fifth episode of bacterial vaginosis (BV) in the past year. She has only been sexually active with her husband. She has tried several courses of topical metronidazole, oral metronidazole, and douching. She has tried eating yogurt and consumes cranberry drinks every day. However, she has had no improvement in her malodorous vaginal discharge. She is frustrated and wants your opinion.

Question

Which one of the following statements regarding this patient's BV is false?

  1. Cranberry suppositories are effective for recurrent BV
  2. Twice-weekly metronidazole gel may reduce recurrences of BV
  3. Biofilm containing Gardnerella vaginalis and Atopobium vaginae is prominent in BV
  4. A probiotic, Lactobacillus casei rhamnosus, may help restore vaginal homeostasis
  5. The presence of Clostridiales and Megasphaera bacteria is highly associated with BV

Discussion

Bacterial vaginosis is the most common vaginal infection affecting women of childbearing age. Women with BV are at increased risk of sexually transmitted infections, low-birth-weight infants, and a substantial reduction in quality of life. Recent molecular studies have elucidated the role of a specific vaginal ecology involved in the pathogenesis of BV.12,13 Bacterial vaginosis is due to a change in the local ecology from a flora of predominant lactobacilli to one of various anaerobic bacteria. A vaginae and Gardnerella are often associated with biofilm production, and finding Megasphaera species or Clostridiales bacteria (BVAB1, BVAB2, and BVAB3) is exquisitely sensitive for the diagnosis of BV. Although short-term treatment with metronidazole or clindamycin is very effective, recurrence rates are around 25% in most women. The best available therapy for women with recurrent BV is a course of either metronidazole or clindamycin, followed by long-term, twice-weekly metronidazole gel. A recent study found that vaginal capsules containing L casei rhamnosus may be effective in restoring the vaginal microflora.14 Although cranberry supplements reduce adherence of E coli in the urinary bladder, they have not been shown to be effective in preventing BV recurrence.

Clinical Pearl

The best available therapy for women with recurrent BV is a course of either metronidazole or clindamycin, followed by long-term, twice-weekly metronidazole gel.

CASE 6

A 65-year-old man with chronic lymphocytic leukemia (CLL) presents to your office with a 3-day history of a pruritic erythematous eruption beginning on his right flank. His last treatment for CLL was 3 months ago with fludarabine, cyclophosphamide, and rituximab. He has had childhood varicella and received the zoster vaccine the year before he was diagnosed as having CLL. At presentation, he has a temperature of 39.4°C, and the rash has spread from the right to the left side of his trunk and back. His leukocyte count is 33.0 × 109/L, with 80% lymphocytes and an absolute neutrophil count of 6.5 × 109/L.

A swab of the flank lesions was positive for varicella zoster virus by polymerase chain reaction.

Question

Which one of the following measures would be most appropriate for this patient?

  1. Prescribe valacyclovir (500 mg once daily for 7 days) and schedule a follow-up visit after completion of valacyclovir therapy
  2. Admit the patient, place him in contact isolation, and begin intravenous acyclovir
  3. Admit the patient, place him in contact isolation, and begin oral valacyclovir (500 mg twice daily)
  4. Admit the patient, place him in contact isolation, and begin meropenem (1 g intravenously every 8 hours)
  5. Admit the patient, place him in airborne and contact isolation, and begin intravenous acyclovir

Discussion

This patient developed thoracic dermatomal zoster, which disseminated in the setting of immunosuppression from his fludarabine, cyclophosphamide, and rituximab regimen. Fludarabine is associated with a prolonged defect in T-cell—mediated immune function, and rituximab may limit the formation of antibodies. Because of this host defect, this patient's shingles disseminated. These patients often shed varicella virus from the skin and respiratory tract, allowing airborne spread. For this reason, these patients should be placed in an airborne isolation room with negative pressure as well as in contact isolation. Centers for Disease Control and Prevention guidelines recommend that immunocompromised patients with even localized zoster be placed in airborne isolation.15 A recent study documented transmission of varicella from an immunocompetent patient with localized zoster covered with a gauze dressing, causing a nursing home varicella outbreak.16 Varicella zoster virus DNA may be detected in saliva very early after infection or even before the development of symptomatic illness.17 Disseminated varicella in immunocompromised patients should be initially treated with parenteral acyclovir until new lesions stop and systemic symptoms improve, followed by a course of oral valacyclovir.

Clinical Pearl

Aerosolized varicella zoster virus from the skin or respiratory tract may cause infections in patients without direct contact with the affected patient.

Correct answers: Case 1: d, Case 2: c, Case 3: b, Case 4: d, Case 5: a, Case 6: e

REFERENCES

1. Briel M, Schuetz P, Mueller B, et al. Procalcitonin-guided antibiotic use vs a standard approach for acute respiratory tract infections in primary care. Arch Intern Med. 2008;168(18):2000-2007 [PubMed]
2. Williamson IG, Rumsby K, Benge S, et al. Antibiotics and topical nasal steroid for treatment of acute maxillary sinusitis: a randomized, controlled trial. JAMA 2007;298(21):2487-2496 [PubMed]
3. Young J, De Sutter A, Merenstein D, et al. Antibiotics for adults with clinically diagnosed acute rhinosinusitis: a meta-analysis of individual patient data. Lancet 2008;371(9616):908-914 [PubMed]
4. US Food and Drug Administration Information for healthcare professionals: fluoroquinolone antimicrobial drugs. 2009. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm126085.htm. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm126085.htm Accessed January 13, 2010.
5. Clinical and Laboratory Standards Institute MIC Interpretative Standards (mcg/mL) for Streptococcus pneumoniae. Performance Standards for Antimicrobial testing; Eighteenth Informational Supplement M100-S18 Wayne, PA: Clinical Laboratory Standards Institute; 2008.
6. Rybak M, Lomaestro B, Rotschafer JC, et al. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists [published correction appears in Am J Health Syst Pharm. 2009;66(10):887] Am J Health Syst Pharm. 2009;66(1):82-98 [PubMed]
7. Karlström A, Boyd KL, English BK, McCullers JA. Treatment with protein synthesis inhibitors improves outcomes of secondary bacterial pneumonia after influenza. J Infect Dis. 2009;199(3):311-319 [PMC free article] [PubMed]
8. Jarvis WR, Schlosser J, Jarvis AA, Chinn RY. National point prevalence of Clostridium difficile in US health care facility inpatients, 2008. Am J Infect Control. 2009;37(4):263-270 [PubMed]
9. Zar FA, Bakkanagari SR, Moorthi KM, Davis MB. A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile associated diarrhea, stratified by disease severity. Clin Infect Dis. 2007;45(3):302-307 [PubMed]
10. Al Nassir WN, Sethi AK, Li Y, Pultz MJ, Riggs MM, Donskey CJ. Both oral metronidazole and vancomycin promote persistent overgrowth of vancomycin-resistant enterococci during treatment of Clostridium difficile-associated disease. Antimicrob Agents Chemother. 2008;52(7):2403-2406 [PMC free article] [PubMed]
11. Kelly CP, LaMont JT. Clostridium difficile—more difficult than ever. N Engl J Med. 2008;359(18):1932-1940 [PubMed]
12. Menard JP, Fenollar F, Henry M, Bretelle F, Raoult D. Molecular quantification of Gardnerella vaginalis and Atopobium vaginae loads to predict bacterial vaginosis. Clin Infect Dis. 2008;47(1):33-43 [PubMed]
13. Marrazzo JM, Thomas KK, Fiedler TL, Ringwood K, Fredricks DN. Relationship of specific vaginal bacteria and bacterial vaginosis treatment failure in women who have sex with women. Ann Intern Med. 2008;149(1):20-28 [PMC free article] [PubMed]
14. Petricevic L, Witt A. The role of Lactobacillus casei rhamnosus Lcr35 in restoring the normal vaginal flora after antibiotic treatment of bacterial vaginosis. BJOG 2008;115(11):1369-1374 [PubMed]
15. Siegel JD, Rhinehart E, Jackson M, Chiarello L, Health Care Infection Control Practices Advisory Committee 2007 Guideline for isolation precautions: preventing transmission of infectious agents in healthcare settings. Centers for Disease Control and Prevention http://www.cdc.gov/ncidod/dhqp/pdf/guidelines/Isolation2007.pdf Accessed October 29, 2009 [PubMed]
16. Lopez AS, Burnett-Hartman A, Nambiar R, et al. Transmission of a newly characterized strain of varicella-zoster virus from a patient with herpes zoster in a long-term care facility, West Virginia, 2004. J Infect Dis. 2008;197(5):646-653 [PubMed]
17. Mehta SK, Tyring SK, Gilden DH, et al. Varicella-zoster virus in the saliva of patients with herpes zoster. J Infect Dis. 2008;197(5):654-657 [PMC free article] [PubMed]

Articles from Mayo Clinic Proceedings are provided here courtesy of The Mayo Foundation for Medical Education and Research