Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (461 page)

Acinetobacter
species are able to survive in very diverse environments. Although
Acinetobacter
species may be isolated as culture contaminants, they are now well established as important primary and nosocomial pathogens. Infections in virtually all organ systems have been described. Major infections include the following:

   
Wounds
:
Acinetobacter baumannii
emerged as a significant cause of infection in battlefield injuries during the Vietnam conflict and recently in casualties from Afghanistan and Iraq. It is now established as an important cause of wound and burn infections in nonmilitary patients.

   
Hospital-acquired pneumonia
:
Acinetobacter baumannii
causes a significant minority (approximately 10%) of nosocomial pneumonias, both as isolated infections or epidemic outbreaks.

   
Meningitis
:
Acinetobacter baumannii
, along with other gram-negative rods (GNRs), is playing an increasing role as a complication of neurosurgery and external CSF drain placement.

   
Nosocomial bloodstream infection
:
Acinetobacter baumannii
is responsible for up to 2% of nosocomial bloodstream infection, usually in ICU patients. The reported mortality rate is approximately 40%, exceeded only by
Pseudomonas aeruginosa
and
Candida.

   
UTI
:
Acinetobacter baumannii
is an established, but uncommon, cause of nosocomial UTI, usually in patients with indwelling catheters.

Treatment of
A. baumannii
infections poses a significant challenge to clinicians because of intrinsic and acquired resistance. Carbapenem antibiotics are usually effective. Isolates often develop resistance to drugs used to treat these infections. Resistance may quickly emerge to the preferred agents used for nosocomial infections. Definitive treatment should be determined by susceptibility testing of the initial isolate; retesting, to detect emerging resistance, is recommended for subsequent isolates recovered during therapy.

ANAPLASMOSIS AND EHRLICHIOSIS

   Definition

The agents of ehrlichiosis and anaplasmosis are small, obligate intracellular bacterial pathogens. Infection is transmitted primarily by the bite of ticks. Specific diseases show restricted geographic distribution based on arthropod vector ranges.

Human granulocytotropic anaplasmosis (HGA) is caused by
Anaplasma phagocytophilum
, transmitted by
Ixodes scapularis
or
Ixodes pacificus
(black legged tick). Disease occurs in New England and the North Central and Pacific 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 reservoir for HGA in the United States.

Human monocytotropic 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 tail deer is the primary reservoir for HME.

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

   Who Should Be Suspected?

Disease develops 1–2 weeks after the tick bite. Fever is present in most infected patients, but asymptomatic or mild disease is common. Nonspecific symptoms are common, including headache, malaise, myalgias, arthralgias, and nausea and vomiting. Rash occurs in a significant minority of patients with HME but is unusual in HGA. Rash caused by coinfection, like rickettsiosis or Lyme disease, should be considered. Mental status changes or meningeal signs may occur in a minority of patients. Renal and respiratory failures have been described infrequently.

   Laboratory Findings

Culture
: not available for routine diagnostic testing.

Direct examination of peripheral blood or buffy coat smear stained by routine hematologic methods
: 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 a minority (1–20%) of monocytes in patients 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. When HME or HGA is suspected, manual differential examination should be specifically ordered. Automated methods are unlikely to detect abnormalities or trigger manual examinations.

Immunochemical staining
: Immunohistochemical staining may be useful in severe or fatal cases, or for patients with early antimicrobial therapy, which may delay the immune response. Specific staining may be used on affected tissues, like bone marrow, or postmortem tissues, including the spleen, liver, lung, kidney, heart, or brain.

NAAT
: Molecular diagnostic tests have been developed for diagnosis of HME, HGA, and related organisms. PCR may be positive in serum or CSF in acute stage, but moderate sensitivity (60–85%) may limit the utility of these tests; infection is not ruled out by a negative result.

Serology
: Specific antibody response may provide an accurate diagnosis; IFA is the serologic method of choice. Patients are usually negative for specific IgG and IgM in the first week of disease. Therefore, testing paired acute serum sample and another collected 2–3 weeks later is recommended.

A probable case designation may be achieved in patients with a compatible illness in whom a single serum specimen, collected in early acute infection, shows an IFA titer that exceeds a cutoff established by the laboratory that is performing the test. Diagnosis is established by demonstration of a fourfold increase (or decrease) in IFA titer of specific IgG (
A. phagocytophilum
,
E. chaffeensis
, or other
Ehrlichia
species) in paired serum specimens. IgM testing has not been shown to be superior to paired IgG studies.