A. Changes in the structure or composition of the cell envelope that make it more difficult for the antibiotic to gain entrance B

[18.3] An aerobic, oxidase positive organism is isolated from the sputum of a 12-year-old cystic fibrosis patient with pneumonia and lung abscesses. On culture the organisms have a "fruity" odor and form greenish colonies. The etiologic agent of the respiratory tract infection is most likely to be which of the following?

[18.1] D. Pseudomonas aeruginosa is an obligate aerobe that grows on many types of culture media, sometimes producing a sweet or grape-like odor. It often produces a nonfluorescent bluish pigment (pyocyanin) which diffuses into agar or pus fluids. Many strains also produce a fluorescent pigment (pyoverdin), which gives a greenish color. One of the most significant problems with Pseudomonas infections is the high level of natural resistance to many antimicrobials that this widespread environmental opportunist exhibits.

[18.2] E. Clinically significant infections with P. aeruginosa should not be treated with single-drug therapy, because the bacteria can develop resistance when single drugs are employed. The newer quinolones, including ciprofloxacin, are active against Pseudomonas. Quinolones inhibit bacterial DNA synthesis by blocking DNA gyrase. The fluorinated forms of ciprofloxacin and norfloxacin have low toxicity and greater antibacterial activity than the earlier forms. Plasmids code for enzymes that determine the active transport of various antimicrobials across the cell membrane.

[18.3] C. All of the options are potential etiological agents for pneumonias in humans. The laboratory descriptions of the organism best fits Pseudomonas aeruginosa (also see the answer for Question 18.1).

A 48-year-old man presents to the emergency room with two days of crampy abdominal pain, nausea, vomiting, diarrhea, and fever. He has not had any blood in his stool. He denies contact with anyone with similar symptoms recently. He has not eaten any raw or unprocessed foods recently. The only food that he did not prepare himself in the past week was a breakfast of eggs "sunny-side up" and bacon that he had at a diner the day before his symptoms started. On examination, he is tired appearing; his temperature is 37.7C (99.9F); and his heart rate is 95 beats per minute (BPM) while he is lying down, but it increases to 120 BPM when he sits up. His blood pressure is 145/85 mm Hg while lying down and 110/60 mmHg when sitting. The physician interprets this as a positive "tilt test," indicating significant volume depletion. His mucous membranes appear dry. His abdominal exam is notable for diffuse tenderness but no palpable masses, rebound, or guarding. A rectal exam reveals only heme-negative watery stool.

 What is the most likely etiologic agent of this infection?

 What are the most common sources of human infections with this organism?

 Most likely etiology of infection: Salmonella.

 Most common sources of infection: undercooked poultry, eggs, dairy products, or foods prepared on contaminated work surfaces.

Summary: A 48-year-old man with acute gastroenteritis has fever, a positive tilt test, abdominal pain, and diarrhea after eating eggs 1 day before.

CLINICAL CORRELATION

Introduction

This individual has the acute onset of diarrhea and vomiting. The first priorities as with any patient are the ABC's: airway, breathing, circulation. Circulatory status is assessed by monitoring the pulse rate and blood pressure, which may be normal at rest, but abnormal on changing of position. This patient had a rise in 10 BPM heart rate from the lying to the sitting position, and a fall of 10 mmHg of blood pressure. This constitutes a positive tilt test and may indicate a volume depletion of 10-25 percent. Thus, the first therapeutic goal would be volume repletion, such as with intravenous normal saline.

In humans, most cases of nontyphoidal Salmonella result from ingesting contaminated food products. Poultry, eggs, dairy products, or other foods prepared on contaminated work surfaces are the most common sources. Fecal-oral spread is common among children. Live animals, especially exotic pets such as reptiles, have also been identified as sources of infection. Host gastric acid is a primary defense against the organism, and conditions or medications that reduce gastric acidity may predispose to infection. The primary site of invasion of Salmonella is the M (microfold) cells in the Peyer's patches of the distal ileum. M cells internalize and transfer foreign antigens from the intestinal lumen to macrophages and leukocyte. The infection can then spread to adjacent cells and lymphoid tissue. Host inflammatory responses usually limit the infection to the gastrointestinal (GI) tract, but bacteremia can occur. Bacteremia is more common in the children, elderly patients, or those with immune deficiencies, such as AIDS. Gastroenteritis is the most common clinical manifestation of Salmonella infection. Nausea, vomiting, nonbloody diarrhea, fever, and abdominal cramps starting 8-48 hours after ingestion of contaminated food are typical. The illness is generally self-limited and will last from 2 to 7 days.

Enteric fever, or typhoid fever, is a more severe form of gastroenteritis with systemic symptoms that are caused by either S. typhi or S. paratyphi. Symptoms include chills, headache, anorexia, weakness, and muscle aches; and later fever, lymphadenopathy, and hepatosplenomegaly; and in a third of patients a maculopapular rash (rose spots). Symptoms persist for a longer period of time than nontyphoidal gastroenteritis as does the carrier state in a small percentage of infected patients.

Gastroenteritis caused by Salmonella can mimic the signs and symptoms of other forms of infections such as Shigella. Infection with Shigella produces predominantly diarrhea, sometimes grossly bloody as a result of invasion of the mucosa. The infection is also usually self-limited; however, dehydration can occur if diarrhea is severe.

Approach to Suspected Salmonella  Shigella Infection

Definitions

 Rose spots: Papular rash usually on the lower trunk leaving a darkening of the skin, characteristic of typhoid fever.

The diagnosis of gastroenteritis is based on the patient's age, risk factors, exposures, and symptoms. Collection of stool and blood cultures, if fever and other systemic symptoms are present, is necessary for the definitive diagnosis. A direct exam for fecal leukocytes and occult blood may initially help narrow down the differential diagnosis. For example, blood in the stools usually indicates invasive bacterial infection. In cases of bacterial gastroenteritis, final diagnosis is made by culture of the stool for enteric pathogens such as Campylobacter, Shigella, and Salmonella. Although culture of Campylobacter requires specialized media and incubation conditions, both Salmonella and Shigella grow rapidly on routine microbiological media. Because of the fact that stool contains many organisms that are normal flora, stools are also cultured onto selective media to aid in more rapid diagnosis.

Both Salmonella and Shigella are nonlactose fermenters that appear as clear colonies on MacConkey agar. The use of a medium that contains an indicator for production of H2S helps differentiate the two genera. Shigella does not produce H2S and appears as clear or green colonies on a media such as Hektoen enteric (HE) agar, whereas Salmonella appears black as a result of production of H2S. This is only presumptive and further biochemical testing needs to be performed because other organisms also produce black colonies on HE agar. The diagnosis of Shigella can also be made by testing for Shiga toxin directly in the stool. This cannot differentiate Shigella from the enterohemorrhagic E. coli that also produce shiga toxin and are associated with hemolytic uremic syndrome.

Treatment and Prevention

Nontyphoid Salmonella gastroenteritis is usually not treated because it is a self-limited disease, and antibiotics have not been shown to alter the course of the infection. Primary treatment should be supportive including fluid replacement if necessary. Antibiotic treatment is recommended for treatment of bacteremia, long-term carriers, or typhoid fever. Amoxicillin, sulfamethoxazole and trimethoprim (SMX-TMP), or, in areas where antibiotic resistant strains are prevalent (India, Asia and Africa), quinolones can be used. The specific choice of antimicrobial agent should be based on susceptibility testing of the patient's isolate.

In the case of infection caused by Shigella, antibiotic therapy has been shown to be useful, especially in the prevention of person-to-person spread of the disease. Quinolones can also be used to treat, although Shigella therapy should be based on antimicrobial susceptibility testing of the isolate.

Prevention of disease caused by enteric pathogens is based on control of the contaminated source in the environment and good personal hygiene. The thorough cooking of poultry and cooking eggs until the yolk is hard can kill Salmonella and prevent infection. A vaccine does exist for prevention of typhoid fever, which is useful for travelers to endemic areas of the world. The efficacy of the vaccine is thought to be between 50 and 80 percent.

COMPREHENSION QUESTIONS

[19.1] In which of the following sites is Salmonella typhi most likely to be found during the carrier state?

[19.2] A 4-year-old has fever and diarrhea. Blood culture grows a gram-negative rod. This is most likely to be which of the following?

[19.3] Which of the following is a frequent cause of osteomyelitis in patients with sickle cell anemia?

[19.4] Which of the following is mismatched?

[19.1] B. The feces of persons who have unsuspected subclinical disease or are carriers is a more important source of contamination than frank clinical cases that are promptly isolated. The high incidence of Salmonellae in commercially prepared chickens has been widely publicized, possibly related to the use of animal feeds containing antimicrobial drugs that favor the proliferation of drug-resistant Salmonellae and their potential transmission to humans. Permanent carriers usually harbor the organisms in the gallbladder or biliary tract and, rarely, in the intestine or urinary tract.

[19.2] C. Enterocolitis is the most common manifestation of Salmonella infection. In the United States, S. typhimurium and S. enteritidis are prominent, but enterocolitis may be caused by more than 1400 strains of Salmonella. Bacteremia is rare (2-4%) except in immunodeficient persons. Stool cultures may remain positive for Salmonella weeks after clinical recovery. Streptococci and Listeria stain gram-positive, and Shigella organisms rarely, if ever, enter the blood stream from the intestines.

[19.3] C. Hematogenous infections account for about 20 percent of cases of osteomyelitis and primarily affect children, in whom the long bones are infected. More than 95 percent of these cases are caused by a single organism, with S. aureus accounting for 50 percent of the isolates. Group B Streptococci and E. coli are common during the newborn period and group A Streptococci and Haemophilus influenzae in early childhood. Salmonella species and S. aureus are major causes of long-bone osteomyelitis complicating sickle-cell anemia and other hemoglobinopathies. Septic arthritis may be encountered in sickle cell disease with multiple joints infected. Joint infection may result from spread of contiguous osteomyelitis areas. Salmonella infection is seen more often in osteomyelitis than in septic arthritis.

[19.4] B. Organisms requiring high salt concentrations are called halophilic. Usually, this refers to microorganisms that are capable of living or surviving in an ocean or salt water area. Vibrios are especially well known for this ability. Salmonella typhi (typhoid fever) multiply in intestinal lymphoid tissue and are excreted in stools. They are hardy survivors in water sources, but they do not survive in halophilic conditions as well as Vibrios.
CASE 20

INTRODUCTION

A 59-year-old man with emphysema secondary to a 50-pack-year smoking history presents with a fever, chills, chest pain, and cough. He had a "cold" with mild cough and congestion for about 3 days but then had the abrupt onset of more severe symptoms. His temperature has been as high as 39.4C (103F), and he's had shaking chills. His cough is productive of sputum that looks like "rust." When he coughs or takes a deep breath, he gets a sharp, stabbing pain in his left lower chest. He has been taking numerous over-the-counter cold medications without relief and has had to use his ipratropium inhaler more often than usual. On examination, he is quite ill appearing. His temperature is 38.8C (101.9F), pulse is 110 beats per minute, blood pressure 110/60 mmHg, and respiratory rate is 28 breaths per minute. His pulmonary examination is significant for the presence of crackles and rhonchi in the left lower fields and expiratory wheezing heard in all other fields. His heart is tachycardic but otherwise normal on auscultation. The remainder of his examination is normal. His white blood cell count is markedly elevated. An electrocardiogram is normal. A chest x-ray shows a dense infiltration of the left lower lobe along with a pleural effusion on the left side.

 What would you expect to see on Gram stain of a sputum sample?

 What is the likely reservoir from which this patient's pneumonia occurred?

 Most likely Gram stain findings: multiple polymorphonuclear leukocytes (PMNs) and encapsulated gram-positive cocci in pairs and short chains.

 Likely reservoir of this infection: colonization of the upper airway (naso- or oropharynx) and aspiration into the lower airways.

Summary: A 59-year-old male complains of fever and cough, with "rust" colored sputum. A chest x-ray shows a dense infiltration of the left lower lobe and a left pleural effusion.

CLINICAL CORRELATION

Introduction

Streptococci cause a wide range of diseases from localized skin and soft tissue infections to systemic infections such as necrotizing fasciitis, endocarditis, and arthritis. Streptococcus pyogenes is commonly associated with pharyngitis and its sequelae of rheumatic fever and glomerulonephritis, in addition to the skin and soft-tissue infections previously mentioned. Streptococcus agalactiae is most well known for its association with neonatal meningitis following vaginal colonization of the pregnant women.

Streptococcus pneumoniae is a cause of otitis media, sinusitis, bronchitis, pneumonia, and meningitis. Streptococcus pneumoniae (pneumococcus) is the most frequent cause of bacterial pneumonia, otitis, and meningitis. It commonly colonizes the upper airways in humans, more frequently in children than adults. Pneumococcal diseases occur when organisms spread from the site of colonization to a distant, susceptible site. Pneumonia occurs when pneumococcus is aspirated into the distal airways and multiplies in the alveoli. Pneumococcal pneumonia typically follows a milder upper respiratory infection. Symptoms of pneumococcal pneumonia include cough, fever, chills, and shortness of breath. Patients may also have increased white blood cells and anemia. A common complication of pneumococcal pneumonia is pleural effusion, which occurs in up to 40 percent of patients. Meningitis either follows sinusitis or otitis or occurs as a result of bacteremic spread of the organisms. Patients that are immunocompromised, elderly, or have underlying heart or lung disease, as well as those that are asplenic, are at higher risk than normal for developing serious disease with S. pneumoniae.

Approach to Suspected Pneumococcus Infection

Definitions

 Rhonchi: A vibration of the chest wall that can be felt with the hand and sounds like a dull roaring or murmuring.

The genus Streptococcus contains multiple species that are differentiated either by their cell wall carbohydrate group antigen, their hemolysis on blood agar, or their biochemical reactivity. Not all Streptococci, including S. pneumoniae, possess a carbohydrate cell wall antigen. Streptococci are facultative anaerobes that require CO2 for growth. Streptococci are gram-positive cocci that form either pairs or chains, whereas S. pneumoniae are elongated, lancet shaped, gram-positive cocci, and are usually in pairs or short chains.

Diagnosis of pneumococcal pneumonia is made based on clinical signs and symptoms, chest x-ray demonstrating infiltration of a single lobe, and sputum Gram stain with many PNMs and gram-positive cocci in pairs and chains. Confirmation of the diagnosis can be made by culturing the organisms from the sputum and/or blood. S. pneumoniae grows rapidly on routine laboratory media including blood and chocolate agar. Colonies on blood agar demonstrate -hemolysis (green color) and may be slightly to extremely mucoid because of their polysaccharide capsule. Colonies are differentiated from viridans streptococci by sensitivity to optochin and bile solubility. Although optochin susceptibility is considered definitive, the addition of bile to a colony will identify the organism as S. pneumoniae if the colony lyses and disappears within a few minutes.

More rapid diagnosis of pneumococcal pneumonia can be made using the urinary antigen test.