Case 1 introduction

Because H. pylori is primarily transmitted person to person via fecal-oral route, the best prevention is improving hygiene by frequent hand washing, especially before meals. In symptomatic patients who are positive for infection with H. pylori, combination therapy is needed. This therapy includes (1) a proton pump inhibitor (omeprazole), (2) one or more antibiotics (amoxicillin, metronidazole), and (3) bismuth.

[10.1] A 45-year-old man presents to the hospital vomiting blood. He is diagnosed with a perforated peptic ulcer. The causative agent discovered by gastric biopsy is a spiral gram-negative bacillus. What other long-term complications could this organism cause if not treated?

[10.2] Which of the following is an important distinguishing characteristic of H. pylori as compared to Campylobacter species?

[10.3] A 58-year-old man presents to the clinic with decreased appetite, nausea, vomiting, and upper abdominal pain. If the causative agent is a curved gram-negative rod with urease production, what treatment should be given to this patient?

[10.1] C. H. pylori is the causative agent that can cause Type B gastritis, peptic ulcers, gastric adenocarcinoma, and gastric MALT B cell lymphomas.

[10.2] C. Both Campylobacter species and H. pylori have a curved shape, are oxidase and catalase positive, with polar flagellum. Urease production is the distinguishing factor of H. pylori, and it is the basis of the rapid urease breath test that diagnoses H. pylori infection.

[10.3] B. The combination therapy of proton pump inhibitor, antibiotic, and bismuth is required to eradicate an infection with H. pylori.

A 19-month-old child is brought to the emergency room following a seizure. His mother says that he had a cold for 2 or 3 days with a cough, congestion, and low-grade fever, but today he became much worse. He has been fussy and inconsolable, he would not eat and has slept most of the morning. He then had two grand-mal seizures. He has no history of seizures in the past. His mother reports that he has not received all of his immunizations. She is not sure which ones he's had, but he's only had two or three shots in his life. On examination his temperature is 38.1C (100.5F), his pulse is 110 beats per minute, and he appears very ill. He does not respond to your voice but does withdraw his extremities from painful stimuli. He grimaces when you try to bend his neck. His skin is without rash and his HEENT (head, neck, ear, nose, throat), cardiovascular, lung, and abdominal examinations are normal. His white blood cell count is elevated, and a CT scan of his head is normal. You perform a lumbar puncture, which reveals numerous small gram-negative coccobacilli.

 What organism is the most likely etiology of this illness?

 What component of this organism is the target of vaccine-induced immunity?

 Organism most likely causing this infection: H. influenzae type B.

 Component of this organism that is the target of vaccine-induced immunity: Purified polyribitol phosphate, a component of the H. influenzae type B polysaccharide capsule.

Summary: A 19-month-old boy who has not received many immunizations presents with meningitis. The lumbar puncture shows multiple gram-negative coccobacilli.

CLINICAL CORRELATION

Introduction

Haemophilus species, particularly H. parainfluenzae and H. influenzae nontype B are normal flora in the human upper respiratory tract. These strains can, however, be associated with respiratory infections such as otitis media and bronchitis. H. influenzae type B was the most common cause of pediatric meningitis (ages 2 months to 2 years of age) until the introduction of routine childhood immunization against this bacterium.

Transmission of H. influenzae occurs by close contact with respiratory tract secretions from a patient colonized or infected with the organism. Prior viral infection promotes colonization of the respiratory tract with H. influenzae. Invasive infections such as meningitis occur when the colonizing organisms invade the bloodstream and subsequently the meninges. Usually as a result of H. influenzae type B, the capsule aids in adherence of the organism and evasion of phagocytosis. Neurological sequelae can occur in up to 20 percent of cases of meningitis. H. influenzae B can also be a cause of epiglottitis in young children, which can result in respiratory obstruction requiring intubation.

Up to 50 percent of strains of H. influenzae produce a -lactamase, rendering them resistant to ampicillin. Treatment for H. influenzae meningitis involves the use of a third-generation cephalosporin (cefotaxime, ceftriaxone). Respiratory infections caused by H. influenzae may be treated with antibiotics such as amoxicillin-clavulanate or a macrolide (such as azithromycin.). Routine pediatric immunization with the vaccine against H. influenzae B has reduced the incidence of invasive disease by approximately 90 percent and has also reduced respiratory colonization. H. ducreyi is usually treated with erythromycin or a newer macrolide antibiotic. An alternative for therapy of chancroid includes a fluoroquinolone.

[11.1] A 2-year-old child has high fever, is irritable, and has a stiff neck. Gram-stain smear of spinal fluid reveals gram-negative, small pleomorphic coccobacillary organisms. Which of the following is the most appropriate procedure to follow to reach an etiological diagnosis?

[11.2] Haemophilus influenzae synthesizes immunoglobulin A (IgA) protease, which enables the bacterium to penetrate and invade the host's respiratory epithelium. This is an example of a bacterium's ability to evade the host:

[11.3] An 18-month-old baby girl is suspected to have Haemophilus influenzae meningitis. She has not been immunized with the HIB vaccine. A rapid latex agglutination test is performed with the spinal fluid to make a definitive diagnosis. What chemical component in the spinal fluid are we detecting with this assay?

[11.4] The Haemophilus influenzae vaccine contains which of the following?

[11.5] Cerebrospinal fluid from a spinal tap of a patient complaining of a severe headache, fever, and nuchal rigidity revealed the presence of gram-negative coccobacilli. Further testing revealed growth of the organism on growth factor X and V supplemented chocolate agar, and no hemolysis when grown on blood agar. Which of the following organisms represents the above description?

[11.1] A. The organism in the above description is Haemophilus influenzae. This organism is differentiated from other related gram-negative bacilli by its requirements of a chocolate media supplemented with growth factors, such as X and V factors, and by its lack of hemolysis on blood agar.

[11.2] E. Immunoglobulin A (IgA) is associated with immunological protection of the host at the epithelial boundary. An IgA protease has the ability to breakdown IgA and thereby act as a virulence mechanism enabling the bacterium to invade the host through an unprotected epithelial boundary. Because IgA is an antibody associated with the humoral (specific) arm of the immune system, IgA protease allows the bacterium the ability to evade the specific humoral immunity of the host.

[11.3] E. The latex agglutination test involves the use of latex beads coated with specific antibody that become agglutinated in the presence of homologous bacteria or antigen. This test is used to determine the presence of the capsular polysaccharide antigen of Haemophilus influenzae in serum or spinal fluid.

[11.4] D. Encapsulated H. influenzae contains capsular polysaccharides of one of six types (A-F). H. influenzae type B is an important human pathogen with its polyribose phosphate capsule being its major virulence factor. As a result, active immunity is built using polyribitol phosphate antigens (capsular polysaccharide) of H. influenzae.

[11.5] D. H. haemolyticus and H. influenzae are the only organisms listed above that require both growth factors X and V for growth; however, they can be distinguished from each other in that H. influenzae is hemolysis negative on blood agar, whereas H. haemolyticus is hemolysis positive.

A 45-year-old homeless alcoholic man presents to the emergency room with fever and cough of 4 days duration. The cough is productive of thick, bloody phlegm. He complains of pain in the right side of his chest with coughing or taking a deep breath. He denies any other medical history and says he can't remember the last time he saw a doctor. He doesn't smoke cigarettes, drinks a pint of whiskey whenever he can get it, and denies drug use. On examination, he is dirty, disheveled, and appears malnourished. His temperature is 38.9C (102F), pulse 105 beats per minute, and respiratory rate is 30 breaths per minute. The lung examination is notable for decreased breath sounds and crackles in the right lower, posterior field. His white blood cell count is elevated. A chest x-ray reveals a dense right lower lobe infiltrate with evidence of a pulmonary abscess. Sputum samples are collected for Gram stain and culture, and a blood culture is sent. A bacterial etiology is suspected.

 What is the most likely organism to be isolated in the sputum and blood cultures?

 By what mechanism does this organism commonly develop antibiotic resistance?

 Most likely organism to be isolated: Klebsiella pneumoniae.

 Mechanism whereby Klebsiella commonly develops antibiotic resistance: plasmid acquisition.

Summary: A 45-year-old alcoholic man has developed a bacterial cavitary pneumonia with evidence of a pulmonary abscess.

CLINICAL CORRELATION

Introduction

Klebsiella causes lower respiratory infections, wound soft tissue infections and is a common cause of hospital-acquired urinary tract infections (UTIs). K. pneumoniae is also associated with lobar pneumonia in a person with an underlying debilitating condition such as alcoholism or diabetes. Pneumonia caused by this organism tends to be necrotic, inflammatory, and hemorrhagic and has a high propensity for cavitation or abscess formation. Patients often produce thick, bloody sputum. Because of the destructive nature of the infection and the underlying debility of the patient, pneumonia caused by K. pneumoniae carries a high mortality.

Community-acquired pneumonia is usually the result of spread of organisms that normally reside in the upper respiratory tract into the lower respiratory tract. Organisms that have virulence factors that allow them to survive the host response in the lung can establish an infection. Patients with disruption of their immune defenses are at greater risk of infection. K. pneumoniae pneumonia is therefore considered an opportunistic infection because it is not a common cause of pneumonia in normally healthy patients. Symptoms of bacterial pneumonia are usually nonspecific and include malaise, anorexia, headache, myalgia, arthralgia, and fever. K. pneumoniae produces a severe acute, necrotic, and hemorrhagic pneumonia, which is evidenced by cavitary lung lesions on chest x-ray, pleural effusions, and possible abscess formation or empyema. Because of the hemorrhagic nature of the pneumonia, patients tend to have blood-tinged sputum.

Two uncommon species of Klebsiella are also causes of respiratory disease. K. rhinoscleroma is associated with chronic granulomatous disease of the upper respiratory mucosa (predominantly outside the United States), and K. ozaenae is associated with chronic atrophic rhinitis.

Approach to Suspected K. pneumoniae Pneumonia

Definitions

Chronic obstructive pulmonary disease (COPD): A progressive lung disease that commonly results from heavy smoking and is evident by difficulty breathing, wheezing, and a chronic cough.

Empyema: Accumulation of pus in the pleural space around the lung.

Objectives

1. Know the structure, physiology, and virulence factors of K. pneumoniae.
2. Know the nature of the native and acquired antibiotic resistance of K. pneumoniae.

Discussion

Characteristics of Klebsiella Species

The genus Klebsiella, which belongs to the family Enterobacteriaceae includes five species, with the most clinically significant being K. pneumoniae. Klebsiella pneumoniae is a large, nonmotile, gram-negative rod with a prominent polysaccharide capsule. The capsule is antiphagocytic and retards leukocyte migration into an infected area.

Another virulence factor of K. pneumoniae is its propensity to develop resistance to multiple antibiotics. All strains of K. pneumoniae are innately resistant to ampicillin, because of the production of -lactamase. Acquisition of resistance to other antibiotics usually occurs by transfer of plasmids from other organisms. Recently strains of nosocomially acquired K. pneumoniae have been isolated that produce an extended spectrum -lactamase and therefore are resistant to all -lactam antibiotics.