Case 1 introduction

Treatment of uncomplicated pneumonia is usually with either a quinolone or a macrolide such as azithromycin. Complicated or disseminated pneumococcal disease is usually treated with penicillin or cefotaxime depending on susceptibility of the isolate to penicillin. Treatment of the other streptococcal species is usually with penicillin, but in serious infections should be based on the individual isolate susceptibility. Adult and pediatric vaccines directed against pneumococcal capsular antigens are available, and current guidelines recommend universal vaccination of children, persons over the age of 65, and others at high risk for pneumonia, such as persons with diabetes or chronic lung disease.

[20.1] A newborn has a temperature of 39.4C (103F). Blood culture grows gram-positive cocci in chains. This is most likely to be which of the following?

[20.2] A 3-year-old is diagnosed with bacterial meningitis. Cerebrospinal fluid grows out gram-positive cocci in short chains and diplococci. This is most likely to be which of the following?

[20.3] Which of the following is the primary virulence factor of Streptococcus pneumoniae?

[20.4] Which of the following is true regarding meningitis with Streptococcus pneumoniae?

[20.1] B. Most human infections caused by Streptococci involve the group A organisms (Streptococcus pyogenes). The group B Streptococci are members of the female genital tract and are important causes of neonatal sepsis and meningitis. They are usually beta-hemolytic (similar to group A), hydrolyze hippurate and give a positive response in the so-called CAMP test (Christie, Atkins, Munch-Peterson). Detection of the infection and prompt antimicrobial treatment is necessary because the infections may become life-threatening. Streptococcus pneumoniae organisms are important in meningitis cases in young children, but are more frequently seen as diplococci forms rather than long chains.

[20.2] D. Streptococcus pneumoniae is responsible for 10-20 percent of meningitis cases in children ages 1 month to 15 years. Neisseria meningitidis range from 25-40 percent, whereas Haemophilus influenzae may be involved in 40-60 percent. Group A and B Streptococci appear to be involved only 2-4 percent of the time. Under the conditions described above, Streptococcus pneumoniae would be the most likely etiologic agent.

[20.3] E. Bile solubility and optochin sensitivity are presumptive identification tests that identify Streptococcus pneumoniae from other alpha-hemolytic Streptococci. The polysaccharide capsule occurs in dozens of antigenic types, but types 1-8 are responsible for about 75 percent of the cases of pneumococcal pneumonia. Vaccines are available that give approximately 90 percent protection and usually contain 23 types of carbohydrates for the U.S.-licensed preparation.

[20.4] B. Because pneumococci are sensitive to many antimicrobial drugs, early treatment usually results in rapid recovery. Antibody response (host's active immunity) seems to play a diminished role today. Penicillin G is the drug of choice, but 5-10 percent of the isolates in the United States are penicillin resistant (MIC  2 microgram/mL), and 20 percent are moderately resistant (0.1-1 microgram/mL). Resistance to cephalosporins, tetracycline, and erythromycin has been demonstrated, although pneumococci remain susceptible to vancomycin. In reference to penicillin therapy, one rule of thumb is to aim for a concentration of 10 times the MIC in the CSF.
CASE 21

INTRODUCTION

While on call on a Saturday night in July, you receive a call from the mother of a 15-year-old man who developed the acute onset of nausea, vomiting, and diarrhea shortly after returning from an outdoor party that was held at the home of a friend. At the party, a picnic lunch of hamburgers, hot dogs, potato salad, baked beans, and lemonade was served. The food was served on an outdoor picnic table, and the guests were free to eat at any time during the party. None of the food tasted spoiled or tainted. His symptoms started abruptly about an hour after he returned home, which was about 4 hours after he had eaten. He currently is unable to keep down anything. He does not have a fever and has not passed any blood in his stool or vomitus. Prior to calling you, your patient's mother spoke with the hostess of the party, who said that she had heard from three other guests who became ill with similar symptoms.

 What organism is the most likely cause of this patient's illness?

 Your patient's mother requests that you call in a prescription for an antibiotic to treat the infection. What is your response?

 Most likely organism causing this infection: Staphylococcus aureus.

 Response to request to treat with antibiotic: No, the gastroenteritis is caused by a preformed toxin, not by the ingested Staphylococci, therefore antibiotic therapy would be of no help.

Summary: A 15-year-old male with gastroenteritis after eating food at an outdoor picnic. Several other participants also developed similar symptoms.

CLINICAL CORRELATION

Introduction

Staphylococcus aureus is a common colonizer of the human nasopharynx and skin. Infection occurs when the normal skin barrier is disrupted by either surgery or trauma.

S. aureus causes numerous infections, ranging from simple localized skin and soft tissue infections to disseminated disease, such as bacteremia, endocarditis, osteomyelitis, and septic arthritis. Many of the infections caused by S. aureus are toxin mediated, such as toxic shock syndrome, scalded skin syndrome, and gastroenteritis.

Staphylococcal food poisoning, the second most reported cause of food poisoning in the United States, is a result of the presence of enterotoxin. Food is contaminated by a human carrier, with processed meats, custard-filled baked goods, potato salad, or ice cream being common vectors. The toxin rapidly produces nausea, vomiting, and diarrhea, usually within 2-6 hours of ingestion. Further toxin is not produced by the ingested S. aureus, and the disease also rapidly resolves, usually within 12-24 hours.

Other staphylococcal species also frequently colonize human skin but can cause disease in certain situations. Although there are more than 20 other species, the majority of the species isolated are S. epidermidis. The most common predisposing factor for disease with Staphylococci not (S. aureus) is the presence of artificial devices in the patient such as catheters and replacement joints. S. epidermidis produces a slime that allows it to adhere to plastics and form a biofilm that makes it very difficult for antibiotics to penetrate.

Approach to Suspected Staphylococcal Infection

Definitions

Biofilm: Bacteria grow on an artificial surface and form a conglomerate with secreted polysaccharides and glycopeptides.

Superantigens: Antigens, most often bacterial toxins, that recruit a large number of T lymphocytes to an area.

Enterotoxins: Substances produced by bacteria that are toxic to the GI tract that cause diarrhea and/or vomiting.

Objectives

1. Know the structure, physiology, and virulence factors associated with S. aureus and the coagulase-negative Staphylococci.
2. Know the diseases caused by Staphylococci and the mechanisms by which Staphylococci develop antibiotic resistance.

Discussion

Characteristics of Staphylococcus

Staphylococci belong to the family Micrococcaceae, which includes the genus Micrococcus in addition to Staphylococcus. Staphylococci grow rapidly on multiple culture media, in a wide range of environments, including up to 10 percent sodium chloride, and in a broad range of temperatures. Staphylococcus aureus is a nonmotile, nonspore forming, facultative anaerobic gram-positive coccus that commonly colonizes healthy humans and is a frequent cause of disease. It is frequently identified as growing in clusters or clumps. This is a result of the effect of bound coagulase ("clumping factor"), which binds fibrinogen, converts it to insoluble fibrin, and results in aggregation. S. aureus is the only Staphylococcusfound in humans which produces coagulase; other staphylococcal species are commonly identified as coagulase-negative Staphylocci.

S. aureus produces at least five cytolytic toxins, two exfoliative toxins, eight enterotoxins, and toxic shock syndrome toxin. Some of these toxins act as superantigens, which recruit host defense cells that liberate cytokines and, therefore, produce systemic effects. Heating will kill the S. aureus organisms, but not inactivate the enterotoxins, because they are stable to heating at 100C for 30 minutes and are resistant to breakdown by gastric acids.

Of growing public health concern is the rapid spread of antibiotic resistance within S. aureus isolates. Almost all S. aureus produces penicillinase, a -lactamase specific for penicillin. Many isolates have also acquired a gene that codes for an altered penicillin binding protein, PBP2', providing antibiotic resistance to semisynthetic penicillins and cephalosporins as well, including methicillin and nafcillin. Some of these genes will also be associated with resistance to non--lactamase antibiotics, such as quinolones and macrolides. Some S. aureus isolates have been identified recently with reduced sensitivity to vancomycin. The mechanism of this resistance is unknown. Genes that confer resistance can be transferred between organisms by plasmid transfer, transduction and cell-to-cell contact.

The initial diagnosis of staphylococcal infection may be difficult because many of the skin and soft tissue infections mimic those of Streptococci. Definitive diagnosis is made by Gram stain and culture of the infected site as well as blood. Staphylococci are large gram-positive cocci grouped in clusters (Figure 21-1).Staphylococci grow rapidly on routine laboratory media. Their colony morphology is different from Streptococci in that the colonies are larger, white or yellow instead of grey. They also can be differentiated from Streptococci by a positive catalase test (reactivity with hydrogen peroxide). S. aureus is -hemolytic on blood agar medium and is differentiated from the other Staphylococcus species by production of coagulase or positive latex agglutination for Staphylococcusprotein A. Further confirmation of the identification of S. aureus is not necessary; however, many commercially available identification systems can identify the organism based on biochemical reactivity. A selective media such as mannitol salts agar, which also differentiates S. aureus from other staphylococcal species is available, but not often used in clinical laboratories.

Treatment of local wound infections without systemic symptoms does not usually require treatment with antibiotics; however, in the cases of more complicated infections or presence of fever, antimicrobial therapy is usually warranted. Although nafcillin is the drug of choice for staphylococcal infections, because of the high percentage of strains that are resistant to methicillin and nafcillin, initial treatment in hospitalized patients is usually with vancomycin until the susceptibility results are available. Oral antibiotics, such as, rifampin and sulfamethoxazole and trimethoprim (SMX-TMP) or clindamycin can also be used dependent on the susceptibility of the isolate. Treatment of Staphylococcusnon-aureus is with vancomycin, because the majority of isolates are resistant to nafcillin.

Control of S. aureus involves strict adherence to hand washing policies, particularly in the hospital setting. The organism can easily be spread from person to person. Colonization with S. aureus is usually transient; however, an attempt can be made in some situations to decolonize the nares by using intranasal mupirocin and/or the skin by using oral antistaphylococcal antibiotics in combination with topical agents.

COMPREHENSION QUESTIONS

[21.1] A 12-year-old girl was playing soccer when she began to limp. She has pain in her right leg and right upper thigh. Her temperature is 38.9C (102F). X-ray of the femur reveals that the periosteum is eroded, suggestive of osteomyelitis. Blood culture yields gram-positive bacteria. The most likely etiologic agent is which of the following?

[21.2] An outbreak of staphylococcal infection involving umbilical cords of seven newborn babies was reported in the nursery. Bacteriological survey reveals that two nurses have a large number of Staphylococcus aureus in the nasopharynx. What test should be performed to determine whether these nurses may have been responsible for the outbreak?

[21.3] Virulence factors of Staphylococcus aureus include all of the following except one. Which one is this exception?

[21.4] Short incubation food poisoning, caused by ingestion of preformed enterotoxin, is caused by which bacteria listed below?

[21.1] C.Staphylococci, especially S. epidermidis, are normal flora of the human skin and respiratory and gastrointestinal tracts. Nasal carriage of S. aureus, the pathogen, occurs in 20-50 percent of humans. Abscesses are the typical lesion of S. aureus. From any one focus, organisms may enter the bloodstream and lymphatics to spread to other parts of the body. In osteomyelitis, the primary focus is generally in a terminal blood vessel of the metaphysis of a long bone, which may lead to necrosis of bone and chronic suppuration. S. saprophyticus is usually a nonpathogenic normal flora organism. Listeria is usually transmitted in unpasteurized dairy products, whereas Salmonella enteritidis is primarily intestinal. Streptococcus pneumoniae is primarily a respiratory pathogen, although it is an important central nervous system (CNS) pathogen in children.

[21.2] A. Bacterial viruses (bacteriophages or phages) can attach to separate receptors on the cell walls of various strains of S. aureus. Different specific receptors have been identified and used as the basis of epidemiological typing of pathogenic S. aureus strains. Typical cultures from the outbreak and strains obtained from personnel can be subjected to a standardized procedure using a series of bacteriophages that attack S. aureus strains. This procedure can readily identify the source of the outbreak organism if it came from a medical care worker.

[21.3] D. M proteins are virulence factors of group A Streptococci (Streptococcus pyogenes). All of the other listed virulence factors may be found routinely in S. aureus bacteria.

[21.4] A. Of the options given the best answer is S. aureus, as a result of enterotoxin production in food. None of the other strains listed produce enterotoxins that result in short-term gastroenteritis.
CASE 22

INTRODUCTION

A 20-year-old man presents for evaluation of a rash that he thinks is an allergic reaction. For the past 4 or 5 days he has had the "flu," with fever, chills headache, and body aches. He has been taking an over-the-counter flu medication without any symptomatic relief. Yesterday he developed a diffuse rash made up of red, slightly raised bumps. It covers his whole body, and he says that it must be an allergic reaction to the flu medication. He has no history of allergies and takes no other medications, and his only medical problem in the past was being treated for gonorrhea about 2 years ago. On further questioning, he denies dysuria or penile discharge. He denies any genital lesions now, but says that he had a "sore" on his penis a few months ago that never really hurt and went away on its own after a few weeks so he didn't think much about it. On exam, his vital signs are all normal. He has palpable cervical, axillary, and inguinal adenopathy. His skin has an erythematous, maculopapular eruption covering his whole body including his palms and soles of his feet. No vesicles are noted. His genital examination is normal.

 What organism is the likely etiology of this disease?

 What disease and stage does this patient have?

 What microscopic examination could confirm this diagnosis?

 Which serologic tests could assist in his diagnosis?

 Most likely causative organism: Treponema pallidum.

 Disease and stage: The patient has syphilis, more specifically secondary syphilis.

 Microscopic examination to confirm the diagnosis: Examination by darkfield microscopy of exudates from skin lesion could confirm the diagnosis of Treponema pallidum infection and secondary syphilis.