Residents of long-term care facilities or hospitals and significant exposure to antibiotics are risk factors for infection.

Wounds: Acinetobacter baumannii emerged as a significant cause of infection in battlefield wounds and those acquired during natural disasters. It is now established as an important cause of hospital-acquired wound and burn infections.

Hospital-acquired infections: Acinetobacter baumannii causes a significant cause of hospital-acquired infections, most frequently pneumonia, catheter-associated bloodstream infection, surgical site infections, and UTIs. Infections may occur as isolated infections or epidemic outbreaks.

Human granulocytic anaplasmosis (HGA) is caused by Anaplasma phagocytophilum, transmitted by Ixodes scapularis or Ixodes pacificus (blacklegged tick). Disease occurs mainly in New England and the North Central United States. Like Borrelia burgdorferi, HGA may cause coinfection with other agents transmitted by Ixodes ticks. Deer and the white-footed mouse are the primary reservoirs for HGA in the United States.

Human monocytic ehrlichiosis (HME) is caused by Ehrlichia chaffeensis and is transmitted by the lone star tick, Amblyomma americanum. Disease is seen in the South and mid-Atlantic, the Central United States, and some areas of New England. The white-tailed deer is the primary reservoir for HME.

HME and HGA are national notifiable diseases, reportable to the CDC and local departments of public health.

When HME or HGA is suspected, manual differential examination should be specifically ordered. Automated methods are unlikely to detect abnormalities or trigger manual examinations.

Examination may demonstrate organism-filled vacuoles (morulae) in the cytoplasm of infected cells. Inclusions in granulocytes may be seen in 20-80% of patients with confirmed HGA, but in monocytes in a minority of patients (1-20%) with HME.

The diagnosis of HGA or HME is not ruled out by a negative smear examination. Disease should be confirmed by specific serology or other definitive test.

Cultures: Alert the laboratory prior to submitting specimens. B. anthracis grows rapidly on standard laboratory media. Specimens from sites of primary infection may include vesicular fluid, swab, or tissue from below
the leading edge of cutaneous lesions, lower respiratory secretions/sputum and mediastinal aspirate for inhalational, feces and peritoneal fluid for GI, CSF for meningitis, or specimens from other infected sites. Blood cultures should be submitted for all patients with suspected anthrax.

Gram stain: Shows large GPBs; may form short chains. Capsules may be apparent. Spores may be seen in subcultures.

Catscratch disease (CSD): Cats serve as the primary reservoir for B. henselae. Infection most commonly manifests as CSD. Almost all patients with CSD present with a cutaneous lesion at the site of inoculation and regional lymphadenopathy. Skin lesions appear within 3-10 days after inoculation and may show vesicular, erythematous, and papular phases. Lesions are minimally symptomatic and resolve after several weeks, healing without scarring. Primary lesions may occur on the mucous membranes or conjunctiva. Tender solitary lymphadenopathy, typically with overlying erythema, develops in the 2nd or 3rd week after infection but may be delayed up to several months. In uncomplicated cases, lymphadenopathy usually resolves within 1-4 months. B. henselae may be suspected in patients with culture-negative endocarditis.

Bartonella quintana was associated with trench fever during World War I. Trench fever is transmitted by the body louse; patients present with fever, malaise, sweats and chills, conjunctivitis, retro-orbital pain, back and neck pain, and anterior tibial pain. Fever is often periodic, with febrile episodes typically occurring 5 days apart. In recent years, B. quintana has emerged as a cause of “urban trench fever” in indigent populations with bacteremia and endocarditis, peliosis, and bacillary angiomatosis (BA), primarily in patients with AIDS. Suspect infection in patients with culture-negative endocarditis, vascular proliferative lesions, like BA, or cystic lesions of the liver or other internal organs (peliosis).

Direct examination and histopathology: Histopathologic examination may provide strong support for diagnosis of bartonellosis. Demonstration
of typical granulomas and typical organisms (Warthin-Starry stain) strongly supports the diagnosis in early CSD. In BA, there is H&E staining of vascular proliferation. Lesions show eosinophilic debris; Warthin-Starry staining reveals masses of small bacteria.

Molecular diagnosis: Sensitive and specific molecular diagnostic assays have been described. PCR and related methods are playing an increasing role in the diagnosis of infections caused by Bartonella species, when available. There are no FDA-approved methods, however.

Serology: The sensitivity and specificity of serologic assays are not high, limiting their utility for the diagnosis of bartonellosis. Assays that report antibody titer are recommended. Serology is limited because of possible cross-reactions with other Bartonella species and other, unrelated organisms. The prevalence of seropositivity in general populations may be significant, suggesting that asymptomatic Bartonella infection is common. In CSD, B. henselae IFA IgG titer of ≥1:256 is consistent with recent infection, supporting a diagnosis of CSD. Titers ≥1:64 to 128 are suggestive but should be repeated after 2 weeks to confirm diagnosis; titers <1:64 indicate that recent infection is unlikely. A positive reaction for B. henselae IgM strongly supports recent infection, but IgM production is typically brief.

Culture: Though isolation of Bartonella in culture provides a definitive diagnosis, cultures are usually negative. Isolation is improved by the use of freshly prepared SBA and chocolate agar, incubated for >7 days at 35-37°C in a humidified atmosphere with 10% CO₂. The lysis centrifugation method is recommended for blood cultures to detect Bartonella bloodstream infections. If routine blood culture systems are used, incubation >7 days, with terminal subculture and acridine orange staining, may improve isolation.

Cultures: Blood and bone marrow cultures are specimens of choice for diagnosis. Other infected patient samples may also be submitted for culture.

Serology: Testing should be requested for agglutinating and nonagglutinating antibodies. Acute serum samples should be collected, followed by convalescent samples several weeks later. IgM titers are increased within the first 1-2 weeks of acute infection; there is a transition to IgG production after the 2nd week. Titers fall in response to effective therapy.

Respiratory tract: Mycoplasma pneumoniae is a significant cause of community-acquired pneumonia, typically presenting with upper respiratory tract symptoms and tracheobronchitis. Extrapulmonary symptoms are presumably caused by an autoimmune response to primary pulmonary infection. Extrapulmonary manifestations include arthritis, hemolytic anemia, and neurologic diseases (meningoencephalitis, cranial nerve palsy, ascending paralysis, transverse myelitis).

Genital tract: Ureaplasma urealyticum, U. parvum, Mycoplasma hominis, and Mycoplasma genitalium are primarily sexually transmitted, but vertical transmission is documented. Neonatal Ureaplasma infection is usually associated with pneumonia and possibly bronchopulmonary dysplasia and bacteremia. In adults, U. urealyticum causes urethritis. Infection during pregnancy may be associated with chorioamnionitis and postpartum fever.

Culture: Because of the lack of a rigid cell wall, these organisms do not stain with Gram stain. A DNA stain, like acridine orange, may demonstrate organisms in infected tissue. Culture of U. urealyticum or M. hominis from infected specimens shows good sensitivity in laboratories able to perform the special culture techniques. Special blood culture media and processing are needed to isolate these organisms from blood.

Molecular diagnostic testing: Nucleic acid amplification assays have been developed for U. urealyticum and the Mycoplasma species.

Chlamydia genital tract infection. Chlamydia trachomatis is the most common cause of sexually transmitted bacterial infections in industrialized nations; serovars D through K are responsible for these genital infections. Serovars L1, L2 (including a and b variants), and L3 are responsible for lymphogranuloma venereum (LGV), a systemic sexually transmitted infection (STI) most commonly encountered in developing countries.

Trachoma: Trachoma refers to chronic C. trachomatis conjunctivitis, usually caused by serovars A, B1, B2, and C. Infection leads to corneal scarring and, in late stages, blindness.

Chlamydia pneumoniae is most commonly associated with lower and upper respiratory tract infections. This pathogen has been implicated in a significant minority (approximately 15%) of community-acquired “atypical” cases of pneumonia.

Chlamydophila psittaci infection causes psittacosis. Birds are the natural reservoir for this organism. Human infection is acquired by inhalation of infectious organisms directly shed from birds or from organisms in their environment. Patients usually present with nonspecific symptoms in acute infection, including flu-like illness: fever, severe headache, hepatomegaly, splenomegaly, and GI symptoms. Chronic pneumonitis may develop.

Molecular diagnostic testing: NAATs are considered the gold standard for the diagnosis of genital C. trachomatis infections. FDA-approved kits are available for endocervical, urine, urethral specimens, and liquid-based Pap test specimens. The use of self-collected vaginal swab or “first-catch” urine specimens (without precleansing) provides reliable results and may improve patient compliance with testing. The sensitivities reported for NAATs range from approximately 90-97%; the specificities are >99%. NAATs have been described for detection of C. pneumoniae, which are the preferred methods when specific diagnosis is required.

Culture: Isolation of C. trachomatis in culture remains an important technique for diagnosis of nongenital infections and is considered the standard for evidence in medicolegal cases, such as rape and child abuse. For optimal isolation, it is critical to collect samples that contain the host cells infected by chlamydia and to transport in conditions that will maintain the viability of the organisms. For detection of genital infections, the sensitivity of tissue culture is approximately 65-85%, with specificity near 100%. There is limited availability for culture isolation for C. pneumoniae or C. psittaci.

Direct detection: Direct flourescent antibody (DFA) staining kits are available for direct detection of C. trachomatis from genital specimens. Slides must be carefully evaluated to ensure adequate specimen collection (i.e., the presence of columnar epithelial cells). Under optimal conditions, the sensitivity of DFA is approximately 80% with specificity >98%. Typical intracytoplasmic inclusions in epithelial cells of Giemsa-stained smears from conjunctival scrapings are found in 50% of patients with C. trachomatis conjunctivitis.

Serology: Serologic testing is not helpful for the diagnosis of acute genital infection caused by C. trachomatis. Serology may be useful to support diagnoses of psittacosis, LGV, and C. pneumoniae respiratory tract infections.

Culture: Isolation of toxigenic C. difficile, using selective anaerobic culture, is considered the “gold standard” for diagnosis. Toxin production by isolates must be documented and may be confirmed by PCR, antigen, or cytotoxicity assays. The complexity and turnaround time required for toxigenic culture assays have limited their use for routine testing.

Cytotoxicity assays: These assays are based on detection of the cytotoxic effect of C. difficile toxin B using stool filtrate on cultured eukaryotic cells.

Toxin EIA: Enzyme immunoassays allow rapid detection of C. difficile toxin B or both toxins A and B. Because of their simplicity and rapid turnaround time (<1 hour), EIA tests have been widely used for diagnosis of CDI. EIA assays have shown high specificity (>95%), but the sensitivity of different assays is variable, ranging from approximately 60-95%, which has limited their use as sole diagnostic testing in critically ill patients or infection control investigations.

Antigen detection: Detection of C. difficile-specific glutamate dehydrogenase (GDH) antigen may be used in algorithms to screen stools for C. difficile. Sensitivities range from 70 to >95%. Toxin must be documented in GDH antigen-positive specimens because nontoxigenic C. difficile strains are detected by this assay.

Molecular diagnostic testing: PCR assays that target the toxin B gene have emerged as clinically important assays for the diagnosis of CDI. Reported performance of molecular diagnostic assays has shown S/S both in the range approximately 95-99% for the presence of toxigenic C. difficile. Note: asymptomatic C. difficile carriage is well described. PCR may be positive for months after clinical recovery from CDI. Also, hospitalized patients may be colonized by organisms without ever developing gastrointestinal symptoms. Molecular tests in these patients may give positive results even in the absence of clinical CDI.

Direct detection: Gram stain typically shows massive tissue necrosis, a lack of PMNs, and the presence of typical organisms (usually large “boxcar” GPBs; the absence of spores on Gram stain is common and does not rule out clostridial infection; other bacterial morphotypes may be seen in mixed infections).

Culture: Anaerobic cultures should be collected. Monomicrobial clostridial infection is typically seen in myonecrosis and other localized infection. Clostridia may be isolated as part of mixed peritoneal and gallbladder infections. Blood cultures may be positive. Primary clostridial bacteremia also occurs and may be associated with GI malignancy, hemodialysis, inflammatory bowel disease, and other conditions.

Core laboratory: WBC count is increased (15,000-40,000/µL). Platelets are decreased in 50% of patients. Protein and casts are often present in urine. Renal insufficiency may progress to uremia. Laboratory findings typical for underlying diseases (e.g., diabetes mellitus [DM]) or complications of clostridial infection are seen. In postabortion sepsis, sudden severe hemolytic anemia is common with conditions such as hypoglobulinemia, hemoglobinuria, increased serum bilirubin, spherocytosis, and increased osmotic and mechanical fragility.

Escherichia coli should be considered in any patient with UTI. Escherichia coli may also be suspected in patients with “traveler’s diarrhea” (abrupt onset, with profuse, watery diarrhea after travel to an endemic area). Enterohemorrhagic E. coli infection may be suspected in patients with diarrhea, especially in patients who develop HUS after diarrheal illness. See the discussion of foodborne causes of diarrhea in Chapter 7, Digestive Diseases.

Klebsiella pneumoniae is associated with severe pneumonia, especially in alcoholics. The pneumonia results in necrosis and hemorrhage; mucoid, “currant jelly” sputum is classic. Bacteremia is seen in a significant number of cases. Klebsiella pneumoniae is also associated with primary or hospital-acquired UTI and hospital-acquired bloodstream, ventilatorassociated, or other extraintestinal infection. Klebsiella pneumoniae isolates are of particular importance in hospital-acquired infections because of their intrinsic and acquired resistance to antimicrobial agents.

Yersiniosis is usually caused by infection with Yersinia enterocolitica, presenting with acute gastroenteritis and abdominal pain. Yersinia enterocolitica is widely distributed in nature and transmitted by the oral route. Swine have been implicated as a reservoir for human infections. Yersinia species are distinctive because growth in culture may be slow.

Yersinia pestis is the cause of plague. In naturally occurring infection, humans are incidental hosts, acquiring infection by exposure to the epizootic cycle between fleas and rodents or through contact with patients with pneumonic plague. Yersinia pestis infection is now rare due to control of the normal rodent reservoir, but Y. pestis is considered a potential risk for development as a bioterror agent; public health officials must be contacted immediately if Y. pestis infection is suspected.

Culture: Enteric GNBs grow rapidly in routine bacterial cultures. Recognition of E. coli strains that cause enterohemorrhagic gastroenteritis may be improved by the use of the differential sorbitol-MAC agar. In the
United States, most isolates are serotype O157:H7. These strains produce Shiga toxin 1 and/or toxin 2, which may be directly detected in stool specimens by antigen testing or NAAT.

Yersinia gastroenteritis is diagnosed by special cultures of stool. Isolates may grow slowly on MAC and show an optimum growth at of 25-32°C. Isolation may be improved by the use of special selective media and incubation, like cold enrichment, but in acute yersiniosis, the bacterial load is high in stool and is usually detected by routine enteric cultures if the laboratory has been alerted to rule out Yersinia. Because of their growth characteristics, automated identification and susceptibility testing may be unreliable. Stool may contain increased WBCs and RBCs, but grossly bloody stool is uncommon. Bacteremia is uncommon but may occur in patients with disorders leading to iron overload, like beta-thalassemia.

Laboratories should have procedures in place for recognition and limitation of handling of Y. pestis isolates. The appropriate public health department should be alerted as soon as Y. pestis infection is suspected on the basis of clinical or laboratory findings.

Susceptibility: The Enterobacteriaceae show a broad range of intrinsic and acquired resistance mechanisms; therapy should be guided by susceptibility testing. All Klebsiella species are intrinsically resistant to ampicillin and ticarcillin. Extended-spectrum beta-lactamases confer resistance to third-generation cephalosporins and most other beta-lactam antibiotics. Klebsiella pneumoniae carbapenemases confer resistance to imipenem, ertapenem, and meropenem in addition to most beta-lactam antibiotics.

Tularemia is caused by F. tularensis, a fastidious, tiny gram-negative coccobacillus. Naturally acquired tularemia is a zoonotic infection involving arthropod and mammalian phases. The normal host species include rabbits, rodents, squirrels and other small mammals, and deer. Domestic livestock, especially sheep, are also susceptible to infection. Human infection is transmitted by direct contact with an infected animal or through the bite of an intermediate arthropod vector (e.g., Dermacentor or other ticks, deer flies).

Francisella tularensis is highly infectious and poses a serious risk for laboratory-acquired infections; clinicians should alert the laboratory when tularemia is suspected so that appropriate precautions and culture techniques are used. The CDC has classified F. tularensis as a potential bioterror agent. Possible or confirmed F. tularensis infections must be reported to state departments of health.

Disease usually occurs 2-10 days after exposure, with ulceration at the site of exposure and painful regional adenopathy (ulceroglandular). Nonspecific symptoms are common, including fever, chills, headache, sweats, severe conjunctivitis, and regional adenopathy. Approximately 20% of patients present with acute onset of fever and abdominal symptoms, including nonbloody diarrhea, vomiting, pain, and tenderness.

Oculoglandular, oropharyngeal, pneumonic, and typhoidal forms of tularemia are caused by direct inoculation or consumption of infected meat or water or inhalation of infectious aerosols.

Gram stain: Tiny faintly staining coccobacilli.

Culture: Samples of blood, bone marrow, primary ulcers, lymph node aspirates, or other infected tissue are inoculated onto special media (added cysteine) and prolonged incubation.

Most Haemophilus infections present as localized infections of the pararespiratory structures, like sinusitis or otitis media. Lower respiratory disease is most commonly manifested as bronchitis in patients with underlying lung disease and may cause significant deterioration of pulmonary function tests, hypoxemia, and dyspnea. Low-grade fever may be seen. Haemophilus influenzae may also cause acute conjunctivitis and endophthalmitis.

Serious invasive disease usually occurs in young children and is caused by Hib, but the incidence has dramatically decreased in regions where the use of the conjugate vaccine is widespread. Epiglottitis, cellulitis of the supraglottic structures, is a life-threatening medical emergency, requiring protection of the airway prior to further interventions. There is typically an abrupt onset of fever, malaise, severe sore throat, and dysphagia. Dyspnea, inspiratory stridor, and drooling develop with progression to severe disease, caused by obstruction of the airway by the swelling of the supraglottic tissue.

Meningitis is a serious manifestation of invasive Haemophilus infection. Presentation is clinically indistinguishable from other causes of childhood meningitis. Cellulitis syndromes (e.g., buccal, periorbital), septic arthritis, osteomyelitis, pericarditis, and empyema are other manifestation of
invasive disease. Blood cultures are usually positive in patients with invasive Hib infections.

Haemophilus ducreyi causes chancroid, an ulcerative STI that occurs primarily in tropical regions. The ulcers of chancroid are painful and have ragged borders with minimal induration. Inguinal adenopathy is common and may progress to draining buboes. Like other genital ulcerative diseases, chancroid increases the risk of transmission of HIV infection.

Culture: Diagnosis of Haemophilus infection depends primarily of Gram stain and culture of infected specimens. Gram staining shows small, pleomorphic, faintly staining gram-negative rods; some pair end to end. Haemophilus species are fastidious but most are efficiently isolated on chocolate agar and in routine blood culture media. Positive cultures from the upper respiratory tract must be interpreted with caution because Haemophilus species are common components of the endogenous flora. Specimens for the diagnosis of chancroid are collected from the margin and undermined base of fresh ulcers. Haemophilus ducreyi is difficult to isolate by culture, requiring specialized enriched media that should be inoculated at bedside.

Antigen detection (for detection of Hib from CSF, serum, or urine): Use of antigen detection is not recommended, having been shown to rarely contribute to the clinical management of patients.

Gastric biopsy: Organisms stain poorly with H&E, but may be demonstrated with Giemsa or silver staining. Tissue may be submitted for organism isolation using special culture techniques or indirectly detected by demonstration of strongly positive urease activity in the gastric biopsy. Tissue diagnosis may be limited because of sampling errors in patchy, localized gastritis.

Breath testing: Strongly positive levels of expired isotope-labeled CO₂ are seen after ingestion of ¹³C- or ¹⁴C-labeled urea. Negative results may be seen after ineffective antibiotic therapy (sensitivity, 90-95%; specificity, 95-99%).

Specific antigen: Detection of H. pylori antigen in feces shows a sensitivity of approximately 90% and specificity of approximately 95% for initial diagnosis and may be used for monitoring response to therapy.

Serology: High levels of H. pylori IgG are predictive of active infection. Antibody levels remain positive for months after successful therapy, so serology has a limited role in early test of cure.

Infants, pregnant women, the elderly, and patients with impaired cellmediated immunity are most at risk. Listeriosis may also occur as outbreaks of foodborne infections, especially related to “deli” meats and unpasteurized cheeses.

During pregnancy, Listeria bacteremia occurs in the third trimester with fever and a flu-like illness. CNS infection is rare, but transplacental fetal infection is common.

In utero infection often results in spontaneous abortion. Neonates show two patterns of infection. An early sepsis syndrome is probably caused by in utero infection, with bacteremia and multiple organ system infection. Late-onset neonatal infection is thought to arise from contamination of infants of vaginal carriers during passage through the birth canal. Infants typically present after 2 weeks with bacteremia and meningitis.

In other groups, clinically significant listeriosis typically presents with bacteremia and/or meningoencephalitis. Severe manifestations are often preceded by fever and GI symptoms, including nausea and vomiting, diarrhea, and abdominal pain. CNS is distinctive because many patients present with parenchymal disease in addition to meningitis, including cerebritis, rhombencephalitis, or brain abscess. Patients may present with meningeal signs, altered consciousness, movement disorders, localized CNS abnormalities, or other symptoms referable to the sites of infection.

CSF findings: Pleocytosis is typical (100-10,000 WBCs/µL). Significant CSF lymphocytosis (>25%) may be seen on CSF WBC differential prior to antibiotic therapy. CSF protein concentration is typically moderately elevated; CSF glucose is reduced in only approximately 40% of patients with CNS infection. CSF findings may lead to misdiagnosis as viral infection, syphilis, Lyme disease, or TB.

Serology: Not usually useful for diagnosis of acute listeriosis.

Early localized disease, during which organisms multiply at the site of inoculation, occurs about 1-4 weeks after tick bite. Erythema migrans (EM) is the characteristic manifestation of this phase and is seen in 60-80% of infected patients and is diagnostic in appropriate patients without further testing. Nonspecific symptoms may occur, including mild fever and flu-like symptoms.

During early disseminated disease, there is hematogenous spread of organisms to multiple organs. Secondary EM lesions may appear days to weeks after early localized infection. Other manifestations of early disseminated disease may present weeks to months after initial infection and include neurologic and cardiac disease.

Late Lyme disease may occur months to years after untreated or inadequately treated primary infection.

Typical EM Lesion: EM is pathognomonic. Treat empirically without specific testing.

Serum serology: It is critical that rigorously validated tests, using validated interpretations, be used for Lyme diagnosis. Virtually, all patients demonstrate positive serology by 4 weeks after primary infection. Testing earlier during acute infection may give false-negative results; repeat testing 4 weeks after a negative result will improve sensitivity. Note: Early antibiotic therapy may inhibit seroconversion.

CSF serology: Demonstration of intrathecal antibody production may be useful for documenting CNS, but not purely peripheral, Lyme disease. Specific B. burgdorferi antibodies are measured simultaneously in serum and CSF. Increased CSF titers, compared to serum, support diagnosis of CNS involvement. Negative results do not exclude CNS Lyme disease.

Molecular tests: PCR is not recommended in seronegative patients. PCR may be positive for CSF in acute lymphocytic meningitis during early disseminated infection (but not in late encephalomyelitis or other neurologic syndrome) or for synovial fluid of joints with active disease in late Lyme disease.

Gonorrhea is an STI of adults. Infection in neonates may be acquired by exposure to contaminated secretions during childbirth. Infections in other prepubertal children must be investigated as a possible indication of child abuse.

Males with gonorrhea most commonly present with urethritis, manifested by dysuria and urethral discharge. Complications include “ascending” infection (epididymitis and seminal vesiculitis, regional adenitis, abscess formation, and urethral stricture) and distant infection by contaminated secretions (e.g., conjunctivitis). Anorectal infections may be asymptomatic but often present with proctitis or rectal pain with purulent discharge and painful defecation. Pharyngeal infection may be asymptomatic but usually occurs as an acute, suppurative pharyngitis with regional adenopathy.

Most infections in women are clinically asymptomatic. Screening women with risk factors for STI is recommended. Symptomatic women with N. gonorrhoeae infection typically present with cervical and urethral infection. Symptoms include vaginal and urethral discharge, pelvic pain, and abnormal vaginal bleeding. Adjacent structures, like Bartholin glands, may become infected by local spread. Ascending infection results in PID. N. gonorrhoeae infection during pregnancy may result in premature delivery or spontaneous abortion, chorioamnionitis, and transmission of infection (conjunctival or pharyngeal) to the neonate.

More than 90% of adults with clinically significant meningococcal infections present with typical signs and symptoms of meningitis. The clinical presentation may be dominated by symptoms of fulminant disease and multiorgan failure. Overwhelming disease may be associated with shock, petechial rash, purpura fulminans, gangrenous necrosis of the distal extremities, or the Waterhouse-Friderichsen syndrome (3-4% of patients).

Meningococcemia may result in sustained bacteremia and seeding of various organ systems. Sustained bacteremia is typically associated with fever, malaise, and leukocytosis. Fulminant disease is usually associated by seeding of the CNS and other organs, DIC, adrenal insufficiency, and multiorgan failure. Meningitis should be actively ruled out by clinical and laboratory evaluation in patients in whom meningococcemia is documented.

Gram stain: Gonorrhea may be diagnosed accurately by Gram stain of urethral secretions from symptomatic males. The detection of typical gramnegative diplococci within PMNs is diagnostic (S/S of approximately 95%).

CSF Gram stain is diagnostic in 50-70% of patients with meningococcal meningitis; pyogenic meningitis in which bacteria cannot be found in smear is more likely to be caused by meningococcus than to other bacteria.

Culture: Culture of genital tract specimens for N. gonorrhoeae has high sensitivity and specificity when enriched, selective media (e.g., modified Thayer-Martin) is used and provides isolates for antimicrobial susceptibility testing. Culture should always be submitted for diagnosis of nongenital N. gonorrhoeae infections and for specimens collected for medicolegal purposes (e.g., child abuse, rape).

Culture is the standard for detection of N. meningitidis infection, using specimens from blood, CSF, or other normally sterile sites.

Molecular diagnosis: Molecular tests are considered the gold standard for diagnosis of N. gonorrhoeae genital infection. Tests with S/S > 98% are available, even when patient collected urine or lower vaginal swabs are used. Because nonviable organisms may be detected, test-of-cure assays are not recommended.

NAATs are becoming increasingly available for diagnosis of CNS meningococcal infection.

Core laboratory: Consistent abnormality is not prominent in uncomplicated gonococcal disease. Patients with meningococcal infection typically show laboratory abnormalities associated with sepsis, including possible DIC. CSF abnormalities are consistent with pyogenic meningitis.

Antigen detection: Use of antigen detection is not recommended, having been shown to rarely contribute to the clinical management of patients.

Culture: Pseudomonas aeruginosa grows well on routine laboratory media after overnight incubation. Special selective media are recommended to improve isolation of P. aeruginosa from lower respiratory specimens submitted from patients with CF.

Susceptibility: Susceptibility testing should be performed on all significant isolates. Isolates may develop resistance during prolonged therapy with any antibiotic; testing of repeat isolates may be indicated. Reported susceptibility to beta-lactam and beta-lactam/beta-lactamase combinations implies the need for high-dose therapy for serious infections; combination therapy is often recommended.

Histology: “Doughnut” granulomas in liver biopsy or bone marrow are highly suggestive but not specific for Q fever.

Culture: C. burnetii may be isolated by special cultures, but this testing is not widely available because of the special methods and biosafety level required.

Serology: The basis of definitive diagnosis: IFA testing is more sensitive (approximately 91%) than CF testing (78%). Serum (1:50 dilution) is screened for anti-phase II immunoglobulin.

Screen-positive specimens are tested for anti-phase I and anti-phase II IgG, IgM, and IgA, with titer, and confirmed by titer levels or significant increases in titer between acute and convalescent specimens. Persistently high titers suggest chronic infection. A single-phase IgG titer ≥1:800 by immunofluorescence is diagnostic and strongly suggests C. burnetii endocarditis; any positive IgM titer is diagnostically significant. High specific IgM titer suggests hepatitis.

Molecular diagnostics: PCR techniques have been described, but there is no FDA-approved kit for NAAT.

Culture: Requires special conditions and is rarely performed.

Histology: DFA of skin biopsy for antigen has S/S of approximately 70%/100% and is the only specific test in early stages of disease. Sensitivity declines after the initiation of antimicrobial therapy.

Serology: Therapy based on clinical suspicion is recommended in early disease because serologic conversion usually requires 7-10 days after onset of symptoms. Quantitative serology (IFA) should be collected during acute infection and then 2-4 weeks later for both IgG and IgM. A ≥4 times increase in IgG or total antibody, or specific IgM, is evidence of recent infection. IgM appears by days 3-8, peaks at 1 month, and lasts 3-4 months. IgG appears within 3 weeks, peaks at 1-3 months, and lasts
for >12 months. Interpretive criteria for RMSF are needed for low-titer results because of potential cross-reactivity with related species or the long persistence of IgG after prior infections.

Molecular tests: PCR has been used to detect R. rickettsii DNA in blood and tissues.

Core laboratory: WBC is mildly elevated; thrombocytopenia may be severe.

Staphylococcus aureus is able to cause pyogenic infection in virtually all organ systems. Cellulitis/impetigo/folliculitis and soft tissue infections are frequent manifestations in healthy outpatient populations. In serious infections, other organ systems may be infected by local invasion or hematogenous spread. Nonsterile needle use facilitates spread of infection and predisposes to disseminated infection. S. aureus is a major cause of hospital-acquired infections.

Common invasive infections include pneumonia, osteomyelitis/septic arthritis, bacteremia/endocarditis, and postsurgical infection. Trauma, including surgical, chronic indwelling catheters, disruption of normal mucocutaneous barriers, implanted foreign material, and other factors increase the risk of S. aureus infection. Serious underlying medical conditions, like neutropenia, also increase the risk and severity of infection.

Food poisoning: Staphylococcal food poisoning is caused by ingestion of food tainted by enterotoxin-producing strains of S. aureus. Symptoms, including crampy abdominal pain, nausea and vomiting, and diarrhea, occur early (2-6 hours after ingestion). Patients are symptomatic for 8-10 hours after onset of illness.

Toxic shock syndrome (TSS): Staphylococcal TSS is defined by fever >38.9°C, diffuse macular rash, desquamation, and hypotension (systolic blood pressure ≤90 mm Hg for adults). This syndrome is caused by the action of TSS toxin-1 (or related toxin), a pyrogenic superantigen elaborated by a colonizing strain of S. aureus. Note that several other species, like Group A Streptococcus, may elaborate similar toxins that produce
an identical clinical presentation. Patients present acutely with vascular congestion, increased permeability of capillaries, and decreased vascular resistance. Hypotension and tissue hypoxia develop as a consequence of the loss of the intravascular blood volume. ARDS and DIC are common complications in patients with severe disease. Diagnosis is possible when signs and symptoms of disease are seen in three organ systems (muscular, GI, liver, bone marrow, CNS, kidney, skin/mucous membranes). TSS is probable when five organ systems are involved and confirmed if all six organ systems are affected.

Lower respiratory tract infection: Stenotrophomonas maltophilia is most commonly isolated from respiratory specimens and may cause approximately 5% of hospital-acquired pneumonias, especially in intubated patients with significant prior exposure to broad-spectrum antibiotics.

Bacteremia: Stenotrophomonas maltophilia bacteremia is most commonly hospital-acquired, caused by indwelling catheter or other site of primary infection.

Wound infections: Stenotrophomonas maltophilia is a relatively common cause of traumatic wound and soft tissue infections. Metastatic cellulitis has been described in oncology patients with neutropenia.

Culture: S. maltophilia grows well on routine laboratory media after overnight incubation.

Susceptibility: With few exceptions, penicillins (including beta-lactam/beta-lactamase combinations), cephalosporins, quinolones, and aminoglycosides are ineffective for S. maltophilia infections. TMP/SMX is the treatment of choice; alternative agents include ceftazidime, chloramphenicol, levofloxacin, minocycline, or ticarcillin-clavulanate.

Group A Strep