Acinetobacter

Acinetobacter baumannii is a pleomorphic aerobic gram-negative bacillus (similar in appearance to Haemophilus influenzae on Gram stain) commonly isolated from the hospital environment and hospitalized patients. A baumannii is a water organism and preferentially colonizes aquatic environments. It is also a natural inhabitant of soil. This organism is often cultured from hospitalized patients' sputum or respiratory secretions, wounds, and urine. In a hospital setting, Acinetobacter commonly colonizes irrigating solutions and intravenous solutions.

The Acinetobacter has more than 50 species, most of which are nonpathogenic environmental organisms. The most common infection-causing species is A baumannii, followed by Acinetobactercalcoaceticus and Acinetobacterlwoffii.[1]

The organism has several features which contribute to its virulence. Acinetobacter contains fimbriae that can assist in attaching to different surfaces in the environment.[2]  The formation of a biofilm is critical in allowing the organism to survive in dry environmental conditions (ref94}.

Most Acinetobacter isolates recovered from hospitalized patients, particularly those recovered from respiratory secretions and urine, represent colonization rather than infection. Care must be exercised in determining whether the isolate is due to colonization or is truly causing infection. Multiple factors tend to increase the risk of acquiring an Acinetobacter infection, including prior antibiotic exposure, intensive care unit admission, use of a central venous catheter, and mechanical ventilation or hemodialysis use. Acinetobacter species can be transmitted to patients because of their persistence on environmental surfaces and because of colonization of the hands of healthcare workers.[1]

When Acinetobacter infections occur, they usually involve organ systems that have a high fluid content (eg, respiratory tract, CSF, peritoneal fluid, urinary tract). These infections may occur as outbreaks rather than isolated cases of nosocomial pneumonia. Infections may complicate continuous ambulatory peritoneal dialysis (CAPD) or cause catheter-associated bacteruria. The presence of Acinetobacter isolates in respiratory secretions of intubated patients may represent colonization. Acinetobacter pneumonias occur in outbreaks and are usually associated with colonized respiratory-support equipment or fluids.

The 2005 IDSA guidelines for hospital-acquired pneumonia discuss the role of Acinetobacter as a cause of nosocomial pneumonia. Nosocomial meningitis may occur in colonized neurosurgical patients with external ventricular drainage tubes.[3, 4]

A baumannii is inherently resistant to multiple antibiotics.

 

When Acinetobacter causes actual infection, the pathological changes that occur depend on the organ system involved. The pathological changes, as observed in patients with pneumonia, are indistinguishable from those caused by other noncavitating aerobic gram-negative bacilli that cause nosocomial pneumonias. Similarly, Acinetobacter urinary tract infections are clinically indistinguishable from catheter-associated bacteremias caused by other aerobic gram-negative bacilli.

The predominant predispositions to infection include colonization pressure, exposure to broad-spectrum antibiotics, and disruption of anatomic barriers.[1]

 

Frequency

International

Acinetobacter commonly colonizes patients in the intensive care setting. Acinetobacter colonization is particularly common in patients who are intubated and in those who have multiple intravenous lines or monitoring devices, surgical drains, or indwelling urinary catheters. Acinetobacter infections are uncommon and occur almost exclusively in hospitalized patients.

Mortality/Morbidity

Although Acinetobacter is primarily a colonizer in the hospital environment, it occasionally causes infection. Mortality and morbidity resulting from A baumannii infection relate to the underlying cardiopulmonary immune status of the host rather than the inherent virulence of the organism.

Mortality and morbidity rates in patients who are very ill with multisystem disease are increased because of their underlying illness rather than the superimposed infection with Acinetobacter.

Race

Acinetobacter infection has no known racial predilection.

Sex

Acinetobacter infection has no known sexual predilection.

Age

Acinetobacter infection has no known predilection for age.

The prognosis of Acinetobacter infection depends on the underlying health of the host and the extent of organ involvement; it is the same as for other aerobic gram-negative bacillary infections.

Prolonged hospitalization or antibiotic therapy predisposes to Acinetobacter colonization.

Patients with Acinetobacter pneumonias occurring in the context of an outbreak in the intensive care unit (ICU) generally have a history of preceding contact with respiratory support monitors or equipment.

Patients with Acinetobacter colonization often have a history of prolonged hospitalization or antimicrobial therapy (with antibiotics that have little or no activity against Acinetobacter).

Because colonization is the rule and infection is the exception, colonized patients have no associated physical findings.

Patients with Acinetobacter infection have signs and symptoms related to the organ system involved, ie, wound infection, episodic outbreaks of nosocomial pneumonia, CAPD-associated peritonitis, nosocomial meningitis, or catheter-associated bacteruria.

The following is summarized from an article by Go and Cunha (1999):[5]

• Acinetobacter commonly colonizes skin, oropharynx secretions, respiratory secretions, and urine.

• Acinetobacter uncommonly colonizes the gastrointestinal tract and is associated with nosocomial pneumonias (which usually occur as outbreaks), bacteremias, and wound infections.

• Acinetobacter infection is rarely associated with meningitis, endocarditis (native valve infective endocarditis and prosthetic valve endocarditis), peritonitis, urinary tract infections, community-acquired pneumonia, and cholangitis.

Antimicrobial therapy using agents with little or no activity against Acinetobacter predisposes to Acinetobacter colonization.

Residency in an ICU, particularly in the presence of other patients who are colonized with Acinetobacter, predisposes to colonization.

A CBC count is nonspecific, and leukocytosis, even with a left shift, cannot be used to differentiate infection from noninfection or bacterial infection from nonbacterial infection. The CBC count cannot be used to differentiate infection from colonization.

Culture of the appropriate body fluid that is properly transported, plated, and incubated grows A baumannii.

Recovery of the organism from a nonsterile body site (eg, endotracheal secretions, urine in patients with a Foley catheter) does not indicate or imply an infectious pathogenic role.

In outbreaks, Acinetobacter is easily cultured from monitoring devices or biological fluids from multiple patients as part of an epidemiological investigation.

Chest radiography and/or CT scanning or MRI of the chest may be useful in defining the extent of a nosocomial pneumonia caused by any organism.

Tests are related to the organ system involved.

CSF culture is necessary if shunt-associated or ventricular drain–associated meningitis is suspected.

Histological changes caused by Acinetobacter infection are indistinguishable from those caused by other aerobic gram-negative bacilli, except those associated with vessel invasion and cavitation, eg, Klebsiella pneumoniae and P aeruginosa.

Initiate supportive care, depending on the organ system involved.

Colonized or infected lines, drains, shunts, or other devices should be removed or replaced as required.

A consultation with an infectious disease specialist is advised to differentiate colonization from infection and for antibiotic recommendations if infection is present.

Although Acinetobacter colonization rarely results in infection, colonization does precede infection. Colonization in one patient may result in infection in another patient. For these reasons, every attempt should be made to isolate patients who are colonized with Acinetobacter in order to prevent other patients from becoming colonized.

Precautions should be taken to prevent colonized patients from colonizing other patients, particularly in the ICU.

Owing to the propensity of Acinetobacter to develop resistance to antibiotics, current treatment strategies remain limited. Beta-lactam antibiotics are the preferred antibacterial choices for susceptible A baumannii infections. Because of increasing resistance, carbapenems have become an increasingly critical therapeutic option for Acinetobacter infections; however, carbapenem resistance rates for A baumannii have been rising dramatically, both in the United States and globally.[1]  Sulbactam/durlobactam is the first antibiotic approved to treat HABP and VABP caused by Acinetobacter. Results from the phase 3 ATTACK trial showed sulbactam/durlobactam was noninferior to colistin in patients with carbapenem-resistant Acinetobacter infections.[14]  Minocycline may retain antimicrobial activity even against strains resistant to other tetracyclines (including tigecycline), although cross-resistance has been reported.[1] In cases of nonbacteremic drug-resistant Acinetobacter pneumonia, the addition of inhaled colistin can be considered. This approach may minimize toxicity and increase antibiotic delivery to the lung.[1]

A baumannii is intrinsically multidrug resistant. Relatively few antibiotics are active against this organism.[6, 7, 8] Avoid treating colonization, but infection should be treated.

Medications to which Acinetobacter is usually sensitive include the following[5, 9, 10, 11, 12] :

• Meropenem

• Sulbactam/durlobactam

• Colistin

• Polymyxin B

• Amikacin

• Rifampin

• Minocycline

• Tigecycline

In general, first-, second-, and third-generation cephalosporins, macrolides, and penicillins have little or no anti-Acinetobacter activity, and their use may predispose to Acinetobacter colonization. Some strains are sensitive to cefepime, ceftazidime, and sulbactam-containing beta-lactam/beta-lactamase–inhibitor drugs.

Monotherapy and combination therapy have been used successfully (eg, amikacin, minocycline, or colistin ± rifampin). Combination therapy is often discussed and suggested, but data proving lower failure rates or lower rates for the development of resistance are inconclusive. Combination therapy can be considered for empiric therapy when the local rates of antimicrobial resistance to certain antibiotics are high or when the isolate is resistant to several classes of antibiotics. 

Class Summary

Empiric antimicrobial therapy should include one of the agents listed below.

Colistimethate sodium (Coly-Mycin M)

Hydrolyzed to colistin, which acts as cationic detergent that can damage bacterial cytoplasmic membrane, causing leaking of intracellular substances and cell death.

Meropenem (Merrem)

Bactericidal broad-spectrum carbapenem antibiotic that inhibits cell wall synthesis. Effective against most gram-positive and gram-negative bacteria. Has slightly increased activity against gram-negative bacteria and slightly decreased activity against staphylococci and streptococci compared with imipenem.

Sulbactam/durlobactam (Xacduro)

Indicated for treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex (ABC). Sulbactam is a beta-lactam antibiotic and beta-lactamase inhibitor. Durlobactam is a beta-lactamase inhibitor that protects sulbactam from degradation by certain serine beta lactamases. 

Amikacin

Irreversibly binds to 30S subunit of bacterial ribosomes; blocks recognition step in protein synthesis; causes growth inhibition. For gram-negative bacterial coverage of infections resistant to gentamicin and tobramycin. Effective against P aeruginosa.

Use patient's IBW for dosage calculation. The same principles of drug monitoring for gentamicin apply to amikacin.

Polymyxin B

Binds to phospholipids, alters permeability, and damages bacterial cytoplasmic membrane.

Tigecycline (Tygacil)

A glycylcycline antibiotic that is structurally similar to tetracycline antibiotics. Inhibits bacterial protein translation by binding to 30S ribosomal subunit and blocks entry of amino-acyl tRNA molecules in ribosome A site. Indicated for complicated skin and skin structure infections caused by E coli, E faecalis (vancomycin-susceptible isolates only), S aureus (methicillin-susceptible and -resistant isolates), S agalactiae, S anginosus group (includes S anginosus, S intermedius, and S constellatus), S pyogenes, and B fragilis.

Rifampin (Rifadin)

Inhibits RNA synthesis in bacteria by binding to beta subunit of DNA-dependent RNA polymerase, which in turn blocks RNA transcription.

Minocycline (Minocin, Solodyn)

Treats infections caused by susceptible gram-negative and gram-positive organisms, in addition to infections caused by susceptible Chlamydia, Rickettsia, and Mycoplasma.