Acinetobacter baumannii: An Emerging Multidrug-resistant Threat

Thomas D Gootz; Andrea Marra

Disclosures

Expert Rev Anti Infect Ther. 2008;6(3):309-325. 

In This Article

With respect to playing a role in causing disease in immunocompromised patients, A. baumannii exemplifies many parallels with the epidemiological observations made for P. aeruginosa; both organisms were initially thought to be of limited virulence and both have demonstrated a remarkable array of both intrinsic and acquired antibiotic-resistance genes. Before the 1970s, most A. baumannii were fully susceptible to antibiotics. With the increased use of broad-spectrum antibiotics and technological improvements in more complicated invasive procedures, conditions were suitable for this ubiquitous pathogen to acquire multiple mechanisms of resistance and infect a vulnerable patient population.[25] Indeed, A. baumannii exhibits a level of intrinsic antibiotic resistance afforded by its decreased membrane permeability and robust efflux systems. There is much speculation in literature that, in addition to genetic conjugation, some form of natural transformation may contribute to its additional ability to acquire foreign DNA under conditions of selective pressure in the antibiotic-rich hospital setting, which presents a major healthcare challenge.[26,27,28] For example, the increase in carbapenem-resistant A. baumannii in one study was directly traced to the increased use of meropenem.[5] The nature of modern intensive care probably favors the acquisition of antibiotic resistance in A. baumannii and the spread of this organism among patients, since its propensity for infection is characterized by multiple patients in close proximity with increasing use of invasive or indwelling treatments, high antibiotic use, an aging patient population and the potential for patient-to-patient spread via colonized or contaminated healthcare workers and surfaces.[6] Indeed, risk factors for MDR infection are invasive procedures, mechanical ventilation, central venous or urinary catheters, prolonged ICU stay and the use of broad-spectrum antibiotics.[11,18,29]

A. baumannii causes a wide range of serious infections and is a major cause of bacteremia, pneumonia (particularly ventilator-associated pneumonia), meningitis and urinary tract infections.[1] Infections attributed to this organism have been reported around the world and are increasing in incidence.[30,31] It is the cause of 2-10% of all Gram-negative ICU infections in the USA and Europe.[5] Given that the majority of A. baumannii recovered from patients are MDR, treatment of these infections is challenging. There have also been reports of panresistant A. baumannii, which are essentially resistant to every marketed antibiotic.[32,33] Numerous studies have attempted to determine the impact of MDR A. baumannii on patient outcomes; these are complicated by the fact that most of the infections occur in ICU patients, where comorbidities can complicate this question. This is borne out by a study that found that A. baumannii-attributable mortality in hospital patients was 7.8-23%; whereas, in ICU patients, it was 10-43%.[31,32] When compared with MDR P. aeruginosa, MDR A. baumannii infections can have higher mortality rates.[34] Importantly, evidence is accumulating that patients who are infected with MDR strains of A. baumannii have a worse clinical outcome than those infected with more antibiotic-susceptible isolates.[35] In-hospital mortality, length of stay, need for mechanical ventilation and functional status at discharge were all worse in the group of patients infected with MDR strains. This finding may suggest that the acquisition and expression of multiple antibiotic-resistance factors does not compromise the pathogenicity of this organism. However, several studies have found that the main impact of MDR A. baumannii infection is increased ICU stay, with little or no effect on mortality.[31] Somewhat surprisingly, in one study no increase in mortality was seen in cases where initial discordant therapy occurred and, although the mortality rate for MDR A. baumannii infections was observed to be higher than that for susceptible A. baumannii infections, the difference was not statistically significant (26 vs 18%, respectively).[31] This latter result was corroborated in other studies and may indicate that the severity of illness in a given patient prior to infection is the major factor in mortality.[31,36,37,38] Overall mortality rates for nosocomial Acinetobacter infection have been reported to range from 19 to 54%.[39,40,41,42]

Studies performed to examine the relatedness of hospital isolates have indicated that nosocomial A. baumannii strains are highly related and more likely to be MDR than control community isolates, which are typically unrelated within a geographical region and susceptible to most antibiotics.[19,43,44] That A. baumannii isolates recovered from a given hospital are likely to be clonal points to the selective pressures within that hospital, which would be directly related to the antibiotic use. One recent report described the finding that strains of A. baumannii that had infected multiple patients in one hospital contained significantly more integrons in their genomes than the strains that had only infected single patients.[45] Integrons are complex genetic elements, which have been implicated in dissemination of antibiotic-resistance genes. The presence of integrons in these strains suggests that the more antibiotic-resistant isolates (containing more integrons) are more fit for hospital infection than nonintegron-containing isolates. Given the relative frequency of MDR A. baumannii in clinical infections worldwide, it is important to understand the many mechanisms of antibiotic resistance that this organism possesses.

Reports of injured US soldiers returning from Iraq and Afghanistan with MDR A. baumannii infections are becoming increasingly common.[30,46] The nature of these infections is a cause for concern, both because of their severity (osteomyelitis, burn and deep-wound infections) and the resistance exhibited by these isolates.[39]A. baumannii has been shown to be the most frequently isolated Gram-negative organism from war wounds; it may be worth noting that A. baumannii has been reported to have been isolated from wounded soldiers returning from Vietnam in the 1970s,[39] although this latter report is not universally accepted.[47] Studies to determine whether A. baumannii carriage by US soldiers is a major source for infection found that carriage isolates differed from infection isolates and were far more susceptible to a wide range of antibiotics.[48] Carriage rates among US soldiers are low, as are rates of A. baumannii isolation from environmental samples taken in the field; instead, most treatment areas tested positive for this organism.[49]

There have also been a limited number of reports regarding community-acquired A. baumannii infections, with pneumonia, bacteremia and cellulitis being the most prevalent.[32] These patients are typically characterized with additional comorbidities, such as diabetes mellitus, chronic obstructive pulmonary disease (COPD) and/or alcohol abuse.[32] Patients with community-aquired A. baumannii infections were more likely to have acute respiratory distress syndrome, lower platelet counts and disseminated intravascular coagulopathy; these issues translated to a higher mortality rate, on the order of 40-64%, although these isolates were more susceptible to antibiotics than hospital isolates.[50] In one study, the mean survival time for patients with community-acquired pneumonia caused by A. baumannii was 8 days, compared with 103 days for patients with A. baumannii hospital-acquired pneumonia.[50] As with MDR hospital isolates, whether the community isolates have increased virulence or if the increase in mortality is due to the patients' underlying illness is not yet clear.

Interestingly, a study over a 10-year period found that A. baumannii nosocomial infection rates were 54% higher during the summer months than in the November-June period,[51] with the majority being bloodstream infections and pneumonia due to central venous catheters and ventilators, respectively. The same trend was not observed for P. aeruginosa infections. Given that there have been many reports of community-acquired A. baumannii from warmer geographical regions, and that infections with this organism are becoming more prevalent in US soldiers serving in warmer climate zones, it is worrying to speculate that the incidence of A. baumannii infections will increase with the changes in climate we are facing.[32]

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