Cases in Clinical Infectious Disease Practice

By Okechukwu Ekenna

In the era of cost cutting and lack of adequate health insurance for many patients, clinical skills and time spent with patients are not adequately compensated. Yet, these dwindling and underpaid skills – good history taking, observation of and listening to patients, and physical examination of patients – remain very essential to making and reaching a complete and accurate diagnosis. Expensive laboratory and imaging diagnostics while very relevant, should not replace these age-old skills that have served to enhance and maintain the doctor-patient relationship and human connection, a connection that is often necessary for healing.

Cases in Clinical Infectious Disease Practice uses case studies to illustrate how the infectious disease clinician processes and integrates data to arrive at a diagnosis. This type of hands-on approach, invaluable in training programs, is utilized to take the reader through initial patient encounter, through the history and physical examination, to simple laboratory findings and stains, to a final diagnosis, in a way that is easily accessible to clinicians, students, and laboratory personnel working with clinical specimens.

• Appeals to practitioners of all levels, with focus on patients with common problems or complications of common infections without heavy technical language
• Emphasizes basic clinical skills including history taking, observation, epidemiology, and physical exam, as well as simple laboratory tests, explaining how they lead to a reasonable diagnosis
• Presents cases seen first-hand within the community setting, reflective of cases or situations a resident or student is likely to encounter in the real world after training

Cases in Clinical Infectious Disease Practice is an essential resource for clinicians, graduate and medical school students, and others conducting medical and clinical microbiology or infectious disease research on real patients.

• Language: English
• Publisher: Wiley
• Release date: Jul 27, 2016
• ISBN: 9781119044062

Book preview

Table of Normal Laboratory Values*

* Adapted from the 2015 Singing River Health System Adult Normal Laboratory Values. Variations with age and sex are not reflected here. These values are to be used only as a general guide.

Okechukwu Ekenna, MD, MPH, D(ABMM), FACP

Dr Ekenna was born in Aba, Nigeria, where he had his primary school and most of his secondary school education (Dennis Memorial Grammar School in Onitsha). He spent a year as an exchange student at Loughborough Grammar School in Leicestershire, England, and another year in Germany, at Neusprachliches Gymnasium Aue, in Wuppertal-Elberfeld. General Certificate of Education (GCE, Advanced Level) was acquired following attendance at the Modern Tutorial College in London.

He attended medical school at Philipps-Universitaet Marburg/Lahn, Germany, graduating in April, 1979 (Aerztliche Pruefung). He successfully defended his doctoral thesis in June, 1979 (magna cum laude) and spent a year of medical internship in Germany before moving to the United States for Residency and Fellowship trainings in Internal Medicine, Infectious Diseases,and Post-Doctoral Fellowship in Medical Microbiology.

Through the course of his clinical and teaching experiences, he has served as consultant physician and lecturer to several institutions in Nigeria (University of Maiduguri Teaching Hospital) and in the USA. He is presently Adjunct Associate Professor of Medicine (since 1998)at the University of South Alabama, in Mobile, AL. He is in private practice in Pascagoula, MS,and is Consultant in Infectious Diseases to the Singing River Health System (SRHS). He is the Chairman of the Infection Prevention/Control Committee for SRHS. He has active consulting privileges at Ocean Springs Hospital and Singing River Hospital in Pascagoula, MS.

He is a naturalized citizen of the United States.

Dr Ekenna is a member of the American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, and Emerging Infections Network of the Infectious Diseases Society of America. He is a Fellow of the American College of Physicians and Fellow of the Royal Society of Tropical Medicine and Hygiene, London. He is also a member of the Organizing Committee of the African Initiative Group of the American Society for Microbiology.

Dr Ekenna is Board certified in Internal Medicine, Infectious Diseases, and in Medical and Public Health Microbiology. He is also certified in Clinical Tropical Medicine and Travelers' Health. He has a Master's degree in Public Health (MPH). He has authored multiple papers in peer-reviewed journals.

Dr Ekenna is fluent in Igbo (Nigerian), English, German, moderately so in French, and speaks a little Hausa. He is still trying to learn Spanish. His wife thinks of him as a history buff.

Dedication

To my parents: Eze Raymond Onuoha Ekenna and Ugo-eze (Mrs) Gabraeline Urasi Ekenna (née Ezurike), and their recognition of the value of a good education.

Acknowledgments

First, I would like to thank the many patients presented here (who will remain anonymous), who have allowed me to tell their story and use their image to illustrate the clinical points made in this book. We are reminded every day that it is a privilege to care for patients who entrust their lives and well-being to our judgments, often working with incomplete or conflicting data. Many of the presented images have made it easier to tell the stories in this book.

I am grateful to the colleagues who asked me to see their patients and render an opinion. I thank them for their trust, and the confidence reposed in me. It is clear that sometimes there are no clear answers to the complex questions posed by these physicians and their patients.

I also thank the many journal and book publishers who gave us permission to use data and figures from their publications and resources. We have acknowledged them wherever indicated. Those illustrations have served to improve the presentation of the cases in this book.

The Singing River Health System gave permission and approval to use laboratory and demographic data, as well as radiologic images where applicable, without patient identifiers or infringing on patient confidentiality. I am grateful for their support.

Ms Cyndi Aycock, MLT (senior microbiologist), was particularly helpful in working with me to process and preserve many microbiological cultures and specimens over the years, many of which are depicted in this book. She did this with such enthusiasm. Thank you, Cyndi.

Dr Sid Eudy, pathologist, was gracious enough to prepare some of the micrographs used in this book.

Several of my friends and colleagues reviewed this manuscript and offered useful suggestions: John O. Chikwem, PhD, Professor of Microbiology and Immunology, Lincoln University, Lincoln, Pennsylvania; Keith Ramsey, MD, Professor of Medicine, East Carolina University, Greenville, NC, formerly Head of Infectious Diseases at the University of South Alabama (USA) in Mobile, AL, who first recruited me as adjunct faculty at USA; and Abraham Verghese, MD, Professor of Medicine and Vice Chair for the Theory and Practice of Medicine, Stanford University, CA.

Dr Christopher Paddock, of the Centers for Disease Control and Prevention, was kind enough to write a generous preface for me. I thank him immensely.

Ms Cynthia Davis, my office nurse, was very helpful in tracking down some of the patients, so that I could obtain their formal permissions to use their photographs in the book.

I am grateful to John Wiley & Sons, Inc., my publishers, and especially to Ms Mindy Okura-Marszycki and Ms Stephanie Dollan, for trusting me initially with this opportunity; to my project editor, Divya Narayanan, and Anandhavalli Namachivayam, production editor, for working with me intensely to get this book readied for publication on time.

The copy editor, Holly Regan-Jones did a wonderful job to help clear up ambiguities.

Finally, I would like to thank my wife, Chiazo, for her support and encouragement over the several years it took to put this book together. She encouraged me as I worked over the holidays to add small sections to the book, in between other clinical and family responsibilities.

Preface

In the spring of 2007, I received a call from a colleague at the Mississippi State Department of Health who informed me of a patient recently evaluated by an infectious diseases physician from the Gulf Coast. The patient had presented with fever, rash, and an eschar following the bite of a tick. At the time of the call, the patient was no longer symptomatic, for the physician had presumptively and correctly diagnosed the illness as rickettsial infection and prescribed the appropriate antibiotic; however, he was curious to know if there was a way to determine if this illness represented a recently recognized disease known as Rickettsia parkeri rickettsiosis. Remarkably, he had retained the tick removed by the patient. Working with the state health department, the tick was sent to our laboratory at the Centers for Disease Control and Prevention, where we determined that it was in fact infected by R. parkeri, closing the loop and establishing this little-known agent as the cause of the patient's illness.

This episode was my first interaction with Dr Ekenna, the astute infectious disease physician and author of this book. To place Dr Ekenna's diagnostic acumen in greater perspective, he diagnosed four more patients with R. parkeri rickettsiosis over the next several years, which is particularly remarkable when one considers that our laboratory at CDC has identified only about 40 patients with this disease in the entire United States since its discovery in 2002.

The case studies provided in this book are salient examples of Dr Ekenna's keen ability of medical detection, whereby the diagnosis and care of each patient are based on a careful history and physical examination. These fundamental processes represent the pillars of clinical diagnosis and are emphasized considerably during the training of medical students and residents; nonetheless, years of practice and experience are characteristically needed to hone and channel these skills to a level where they can be applied effectively and consistently. The cases described herein illuminate Dr Ekenna's deceptively simple and logical approach to each medical mystery in which he gathers pertinent data relating to person, place, and time and assembles a diagnosis and careful plan of treatment tailored to the complete circumstances of the individual patient. This truly is the art of medicine. In this context, we follow the diagnosis and successful treatment of a financially challenged patient with sporotrichosis, learn of the removal of carious teeth from a patient with Actinomyces israelii endocarditis, and observe the confirmation of a sulfa drug-induced hypersensitivity masquerading as sepsis in a long-suffering patient.

The breadth and scope of cases portrayed in this collection are fascinating. These include a wide spectrum of infectious conditions caused by various common and not so common infectious agents that include mycobacteria, fungi, helminths, spirochetes, and, of course, rickettsiae. Many of the infections are presented as syndromic or uniquely situational processes, such as a section on serious soft tissue infections caused by various Vibrio, Staphylococcus, and Alcaligenes species bacteria identified in patients along the Gulf Coast in the aftermath of Hurricane Katrina. Remarkably, these clinical vignettes originate not from the collective encounters by a large group of specialists at a tertiary care facility in a large metropolitan center, but rather from the professional experience of one doctor working at a small community hospital along the Mississippi Gulf Coast, and reflect the immeasurable good that a thorough and thoughtful physician can provide to the health and well-being of an entire region.

Christopher D. Paddock, MD, MPHTM

Centers for Disease Control and Prevention, Atlanta, Georgia

Introduction

In the era of cost cutting and lack of adequate health insurance for many patients, clinical skills and time spent with patients are not adequately compensated. Yet these dwindling and underpaid skills – good history taking, observation of and listening to patients, and physical examination – remain essential to making and reaching a complete and accurate diagnosis. Expensive laboratory and imaging diagnostics, while very relevant, should not replace these age-old skills that have served to enhance and maintain the doctor–patient relationship and human connection, a connection that is often necessary for healing.

The process of differential diagnosis is particularly relevant in infectious diseases, and still involves what we typically label as the art and science of medicine. This process requires a skill that usually improves with clinical experience, and is not achieved by textbook reading alone.

I have had the privilege and requirement to present on a regular basis real cases seen in my private practice over the last 18 years to medical students, residents, fellows, and faculty as part of my teaching responsibilities with the University of South Alabama in Mobile, Alabama, as well as presenting to the local medical staff on the Gulf Coast of Mississippi. The positive feedback I have received from students, medical staff, and faculty has encouraged me to present some of these cases in this publication. The format chosen is similar to the way I have usually presented them at the teaching conferences, except that they will not be in PowerPoint and will be somewhat abbreviated because of space constraints.

These cases will provide an illustration of how the infectious disease clinician processes and integrates data to arrive at a diagnosis. This type of hands-on approach is not given adequate emphasis these days in our training programs.

The cases presented in this book will take the reader from the initial patient encounter, through the history and physical examination, to simple laboratory findings and stains, to a final diagnosis, in a way that is simple to follow and without the need to cram up a lot of other data.

The book is intended for the practicing clinician or student in clinical training. It should be useful to teaching hospitals involved in the training of medical residents and students of allied health institutions involved in clinical practice. An additional advantage is that the cases presented here do not reflect patients seen at tertiary institutions, but rather in the community setting. They reflect the type of cases or situations the resident or student is likely to encounter in the real world after training.

The cases presented in this book should be within the reach of the average practicing physician and medical resident in training. They should also help practitioners and students in allied health, who may work up clinical specimens referred by clinicians, in their understanding of the thinking of the consultant. The cases will include photographs, illustrations, and microbiological slides as applicable and available. I have added schematic diagrams on the few occasions where it was not possible to obtain permits for patient photographs.

It is hoped that reviewing these cases will enhance the integrated skills and critical thinking of the reader.

Finally, at the end of each case, I will discuss diagnostic aids or clues in the case and practical lessons learned.

How the book should be used and understood

The cases presented were seen between 1997 and 2015, an 18-year period, and include inpatients and outpatients.

The presentations reflect the time and period during which the patients (cases) were encountered. Diagnostic and treatment modalities, therefore, reflect those available at the time and place of care.

All of these cases were consultations provided to physicians practicing in the community setting (whether hospital based or in office practice).

All personal identifiers have been removed (including names of institutions where care was provided), in order to protect the identity of the patients.

However, the dates of patient encounters (consults) have been included for context, as well as the season of the year, as these may provide important epidemiologic clues to making a correct diagnosis.

My suggestion is that you first review the case history and then hazard a diagnosis before turning to the answer and discussion section.

At the end of each case presentation, we will address simple diagnostic clues and any lessons learned from the case.

Chapter 1

Skin and Soft Tissue Infections

Case 1.1 Soft tissue infection following traumatic aquatic exposure

In early September 2010, a 7-year-old boy suffered a laceration injury to the left calf during a recreational boat ride on a coastal river. He was brought to the emergency room (ER) within 2 hours of this accident, after initial cleansing first aid with saline in the field.

The wound was noted to be severe and deep, and was described as partial degloving by the ER physician. The boy's vital signs were stable. Due to the nature of the wound, an orthopedic surgeon was consulted and the patient was taken to surgery within 2 hours for wound washout and closure. X-rays of the leg showed no fractures.

Cefazolin and gentamicin were given preoperatively. The patient received 34 stitches to close the large (>10 cm) complex left calf laceration injury after extensive washout. No cultures were done.

One day later, infectious diseases consult was sought for outpatient oral antibiotic recommendations, in anticipation of discharge home later that day.

The boy's past medical history was unremarkable, except for hospital admission for symptoms of nausea and vomiting 1 year earlier, and ear tubes placed 1.5 years earlier.

His examination was unremarkable except for superficial abrasions on the lower abdomen and right upper arm, and the deep (now sutured) left calf laceration. Temperature was 100.5 °F, but other vital signs were stable.

A combination of trimethoprim/sulfamethoxazole and cefuroxime was recommended as oral antibiotics, and the patient was then discharged to outpatient follow-up.

Six days after discharge from the hospital, he was readmitted because of wound infection. He had failed to take the prescribed antibiotics because of severe nausea.

At surgery, no frank pus was found but serous old blood and drainage were noted. A swab of this drainage was stained and cultured.

The infectious diseases consultant was called (after surgery) to help with additional recommendations. He added ceftriaxone to the vancomycin already prescribed. Examination of the patient the next day found him to be comfortable, afebrile, and eating breakfast. His temperature was normal (97.8 °F). The abdominal skin abrasions were healing, but the left calf was wrapped up following the surgical incision and debridement (I&D) the day before.

Basic laboratory findings were normal (white blood cell [WBC] count was 7300/μL, platelet count 401,000/μL, and creatinine 0.5 mg/dL).

The gram stain of the serous fluid from the wound showed rare WBCs and no organisms. Twenty-four hours later, the culture was reported positive for a gram-negative rod (GNR).

The left calf wound was clean when inspected on day 4 post surgery (Fig. 1.1a).

What are the likely organisms in this patient (differential diagnoses) and why?

c01f001

Figure 1.1a Left calf wound on day 4 post surgery (reproduced with permission). (See insert for color information)

The GNR was found to be oxidase positive, beta-hemolytic on sheep blood agar (BA), and the subculture showed luxuriant growth on all three agar media (BA, chocolate BA, and MacConkey agar) within 24 hours (Fig. 1.1b). It was noted later to be resistant to penicillin/ampicillin-like agents, including carbapenems, but sensitive to second- and third-generation cephalosporins, quinolones, and trimethoprim/sulfamethoxazole, as well as tetracyclines and aminoglycosides.

What is your new diagnosis?

c01f002

Figure 1.1b Luxuriant growth of gram-negative rod on blood agar medium in 24 hours, and comparative growth of the same organism on BA, chocolate BA, and MacConkey agar. (See insert for color information)

The patient was discharged 6 days later to outpatient follow-up on intravenous ceftriaxone after a peripherally inserted central catheter (PICC line) was placed.

Two months later he was doing very well, and underwent plastic surgical repair of the calf laceration (Fig. 1.1c).

What were the clues to the diagnosis?

c01f003

Figure 1.1c Photo taken in March 2011, 6 months after the injury: healed left calf post skin grafting (reproduced with permission).

Case discussion

First, the injury occurred while boating on a river, in possibly brackish water (coastal river). Gram-negative organisms are common and likely to contaminate the wound with such a severe laceration injury. The organism grew rapidly on all three culture media used (BA, Choc BA, and MAC). It was oxidase positive, non-lactose fermenting, mucoid, and beta-hemolytic on sheep BA. It did not require high salt concentration to grow, making certain Vibrio organisms (those that need high, 6.5% salt concentration) unlikely. The sensitivity pattern is also useful (see earlier). The organism turned out to be sensitive to the two agents originally recommended (trimethoprim/sulfamethoxazole and cefuroxime). The child was unable to take the antibiotics because of persistent nausea.

Differential diagnosis

Our differential diagnoses at the onset were Aeromonas or Pleisiomonas, more likely than Vibrio, because of the fresh water or brackish water environment where the injury occurred. The luxuriant growth in all three media was in keeping with the differential diagnoses chosen.

Final diagnosis: Aeromonas hydrophila

Some data from the literature on Aeromonas are shown in Table 1.1a and given below.

Table 1.1a Organisms associated with soft tissue infection following water exposure

* Infection associated with patients with underlying liver disease, iron overload syndromes, and cancer; infections in these high-risk groups are particularly fulminant [1].

Reproduced with permission of UpToDate from Baddour [1].

Sites of isolation of Aeromonas (environmental reservoirs) [2]

Fresh water

Estuarine (brackish) water

Surface water, especially recreational

Drinking water, including treated, well, and bottled

Polluted waters

Waste water effluent sludge

The organism grows at a range of temperatures from 0 °C to 42 °C.

Characterization and classification of Aeromonas [2]

Aeromonads are ubiquitous inhabitants of fresh and brackish water.

They have also been recovered from chlorinated tap water, including hospital water supplies.

They occasionally cause soft tissue infections and sepsis in immunocompromised hosts and increasingly have been associated with diarrheal disease.

Because of recent phylogenetic studies, Aeromonas species have been moved from the family Vibrionaceae to a new family, the Aeromonadaceae.

Microbiologic identification of Aeromonas [2, 3]

Oxidase-positive, polar flagella, glucose fermenter, facultative anaerobic GNR.

Resistant to the vibriostatic agent O/129, and unable to grow in 6.5% NaCl.

Hemolysis is variable but most are beta-hemolytic on BA media.

There are a few useful standard biochemical tests (A. hydrophila is catalase positive and motile, converts nitrate to nitrite, and is urease negative).

Antimicrobial susceptibility tests of motile Aeromonas spp [2]

Most strains are resistant to penicillin, ampicillin, carbenicillin, and ticarcillin.

Most are susceptible to second- and third-generation cephalosporins, aminoglycosides, (carbapenems), chloramphenicol, tetracyclines, trimethoprim/sulfamethoxazole (TMP-SMX), and fluoroquinolones. In the case presented here, the Aeromonas was resistant to carbapenems, ampicillin, and first-generation cephalosporins.

Higher resistance patterns (to TMP-SMX, tetracycline, and some extended-spectrum cephalosporins) have been found in Taiwan and Spain.

Therapy with ampicillin or first-generation cephalosporins is not appropriate.

Lessons learned from this case

Think of wound contamination with any complex laceration injury.

Culture of the wound is critical before antibiotics are prescribed.

No complete closure of wound, especially when environmental contamination is known or anticipated, as in this case.

The patient should be advised to take the antibiotics or report if there are problems, so adjustments may be made. The patient in this case did not take the prescribed antibiotics because of nausea.

Inspect wounds regularly for signs of inflammation or infection (pus, redness, pain, swelling, induration, or drainage).

Think of the epidemiology (type of injury, environment, place, and season of the year) of the injury, and likely organisms expected in the given circumstances

References

1 Baddour LM.Soft tissue infections following water exposure. Available at: www.uptodate.com/contents/soft-tissue-infections-following-water-exposure?view=print#, accessed February 24, 2016.

2 Morris JG, Horneman A. Aeromonas infections. Available at: www.uptodate.com/contents/aeromonas-infections?topicKey=ID%2F3138&elapsedTimeMs=5&source=search_result&searchTerm=Aeromonas+infections&selectedTitle=1%7E28&view=print&displayedView=full, accessed February 24, 2016.

3 Steinberg JP, Burd EM. Other gram-negative and gram-variable bacilli. In: Mandell GL, Bennett JE, Dolin R (eds) Principles and Practice of Infectious Diseases, 7th edn. Philadelphia: Churchill Livingstone, 2010, pp. 3017–19.

Case 1.2 Soft tissue infection of the hand and wrist in an 81-year-old man

An 81-year-old Caucasian male was seen for soft tissue infection of the right hand and wrist.

Infectious diseases (ID) consult was sought on 3/4/09 because of a severe hand and wrist wound following surgery. This patient had extensive flexor tenosynovectomy of the right wrist and drainage of abscess of the palm, plus carpal tunnel release 16 days earlier on 2/16/09.

He had been seen 6 weeks earlier in January elsewhere because of swelling of the right thumb several days after a shrimp fin puncture injury to his thumb. Following computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound studies, he had been started on antibiotics without improvement in the swelling of the thumb. When he began to develop cellulitis of the right arm, he was referred to the orthopedic surgeon for further management. Initially, steroid injection to the right wrist was tried, along with oral clarithromycin, but these treatments did not help the swelling. Incision and debridement was therefore done on 2/16/09. At surgery, thick white, purulent material (pus) was obtained, and sent for culture.

The significant finding in the review of systems was severe pain in the wrist, but no fever.

Past medical history and underlying diseases included the following: Atrial fibrillation, for which he had been on Coumadin (warfarin) for years. He had easy bruising (and may have bled into the wrist?). He had bladder stone removed 2–3 months earlier through cystoscopy. He also had exploratory laparotomy several years earlier, including lysis of adhesions. He had significant generalized arthritis and coronary artery disease (CAD), with coronary artery bypass graft (CABG) surgery more than 3 years earlier, plus cardiac stents 4 years previously. Other underlying diseases included hypertension, gout, and sleep apnea (he was on home continuous positive airway pressure – CPAP).

He was retired after working for many years in the construction business. He stopped smoking 40 years earlier, and stopped drinking alcohol 2 years before the office visit. He had no allergies.

On examination, he was alert, oriented, pleasant, and in no acute distress. The vital signs were as follows: blood pressure (BP) 148/78, respiratory rate (RR) 18, heart rate (HR) 78, temperature 98.6 °F; height 5′9′′; weight 197 pounds.

Head and neck exam was significant for partial dentures with extensive dental work and bridges. No adenopathy was noted. The heart exam showed irregularly irregular heartbeat consistent with atrial fibrillation. The chest showed a healed thin median sternal scar from previous CABG surgery. The rest of the exam other than the extremities showed nothing significant. The upper extremities showed ecchymotic skin changes in the forearms; the right forearm, wrist, and proximal palm surgical site is shown in Fig. 1.2a. The radial artery was palpable.

What are the possible differential diagnoses based on the history and physical exam so far?

What would be your recommendation to