A Decade-Long Study Focused on the Clinical and Microbiological Assessment of Patients Infected by Achromobacter Species

Achromobacter species is a motile, aerobic, oxidase-positive, non-fermentative Gram-negative bacillus (1). This microorganism is widely distributed in the environment and is most frequently associated with healthcare-associated infections (1, 2). The majority of cases occur in patients with some form of immunosuppression, particularly those with hematologic malignancies, with primary bacteremia being the most prevalent clinical presentation (3-6). Additional documented infections include urinary tract infections, abscesses, osteomyelitis, corneal ulcers, prosthetic valve endocarditis, peritonitis, and pneumonia (7-10). Surgical site infections caused by Achromobacter spp. are increasingly reported in the literature (11). In immunocompromised hosts, it is known to cause opportunistic infections, including bloodstream infections, pneumonia, and urinary tract infections (12). The species is ubiquitous in aquatic environments and is capable of colonizing various aqueous solutions, such as dialysis fluids, ultrasound gels, and even disinfectants used in hospital settings (13, 14). Contaminated hospital environments, particularly water-containing equipment and healthcare workers’ hands or gowns, can serve as reservoirs for these pathogens and play a critical role in the transmission of nosocomial infections (15). Resistance to beta-lactams, fluoroquinolones, and aminoglycosides, which are frequently used in empirical treatment, has been increasing in Achromobacter spp. isolates (16). The production of various beta-lactamase enzymes and the activity of efflux pumps play a significant role in the development of this resistance (1).

The aim of this study was to investigate the resistance profile and microbiological characteristics of Achromobacter spp. isolated in a tertiary health institution during a 10-year period. It also aimed to examine the demographic data, treatment protocols, treatment responses, and prognoses of patients in whom Achromobacter spp. was isolated in any sample.

Achromobacter spp. was identified in 212 isolates during the study period. However, only 154 cultures were included in the analysis, as 24 patients were under the age of 18, 21 isolates demonstrated repeating culture positivity, and 13 cultures were deemed colonizations (Figure 1). The median age of the cohort was 52 years, with 68.5% being male. Among the 107 patients, at least one co-morbidity was present, with immunosuppression being the most prevalent (39.6%). The highest rate of isolation (42.9%) was observed from surgical clinics. The most frequently administered antibiotics were piperacillin-tazobactam (25.3%) and meropenem (16.2%). Polymicrobial infections were documented in 50 patients (32.5%). The 28-day mortality rate was 12% (Table 1). Anti-HIV antibody was tested during the hospitalization period, and none resulted in positive. The origin of the isolates is illustrated in Figure 2, showing that 46% originated from abscess and wound samples, 29% from blood, 13% from respiratory specimens, and 9% from urine samples. One percent of the isolates were obtained from samples such as catheter tips or cerebrospinal fluid.

Figure 1.

Flow chart of patients and isolates included in the study

Figure 2.

Types of the isolates

Table 2 shows a comparative analysis of the characteristics, laboratory findings, and prognoses of patients with polymicrobial (n = 50) versus monomicrobial (n = 104) infections. The prevalence of having at least one chronic condition was significantly higher among patients with monomicrobial infections (75% vs. 58%; P = 0.032). Additionally, the history of trauma was more prevalent in monomicrobial cases (16% vs. 8%; P = 0.035). The abscess/wound isolate rate in polymicrobial infections was higher than in monomicrobial infections (36% vs. 68%, P < 0.001), whereas monomicrobial infections were more frequently associated with isolates from blood (P = 0.004) and urine (P = 0.034) samples. No significant difference was observed between the groups in the comparison of white blood cells and C-reactive protein levels before and after treatment. The 28-day mortality rate was 17.6% in patients with monomicrobial infections, compared to 4% in those with polymicrobial infections (P = 0.037).

When comparing bacteremic (n = 45) and non-bacteremic (n = 109) patients, the incidence of hypertension (22% vs. 8.3%; P = 0.017) and coronary artery disease (45% vs. 7.3%; P = 0.003) was significantly higher in those with bacteremia. The prevalence of bacteremia was significantly higher in samples obtained from intensive care units (48% vs. 17%, P < 0.001). Conversely, the rate of polymicrobial infection was more pronounced in non-bacteremic patients (P = 0.004). In terms of antibiotic regimens, the utilization of meropenem was significantly higher in bacteremic patients (44% vs. 16%; P = 0.006). Although the 28-day mortality rate was higher among bacteremic patients (20% vs. 10.5%), this difference did not reach statistical significance (Table 3).

The antimicrobial susceptibilities of isolates are illustrated in Figure 3. Piperacillin-tazobactam exhibited the highest susceptibility rate (70%), followed by imipenem (60%). Resistance to cephalosporins exceeded 50%.

Figure 3.

Antimicrobial susceptibilities of Achromobacter spp. isolates

In this study, 69.5% of patients presented with at least one chronic condition. The rate of immunosuppression was 40%, while malignancy was observed in 26% of the cohort. A laboratory-based surveillance study conducted by Işler et al. in Australia reported that 90% of patients with 195 bloodstream infections had a Charlson Comorbidity Index (CCI) score of 1 or higher, with 19% having a CCI score of 3 or higher (5). The group most frequently affected by Achromobacter spp. infections comprises patients with cystic fibrosis (17, 18), in whom bacterial colonization is likely due to persistent inflammation in the respiratory tract. Furthermore, Achromobacter strains can persist in the respiratory tract through various patho-adaptive mutations, such as biofilm formation, genetic diversification, immune evasion, and the development of antibiotic resistance (19).

In the literature, Achromobacter spp. has been identified as the causative agent of bacteremia in patients with chronic myeloid leukemia (20), cellulitis following allogeneic hematopoietic stem cell transplantation (12), and bacteremia following endoscopic retrograde cholangiopancreatography in individuals with cholangiocarcinoma (21). Achromobacter spp. should be considered a possible pathogen in immunocompromised patients due to its opportunistic character. The incidence of polymicrobial infections was more pronounced in samples procured from abscesses. A meta-analysis that investigated surgical site infections attributable to Achromobacter spp. revealed concomitant infections with bacteria such as Escherichia coli, Morganella morganii, Acinetobacter baumannii, and Stenotrophomonas maltophilia, particularly following intra-abdominal, neurological, thoracic, and gynecological procedures (22).

In a retrospective study of Achromobacter spp. infections in cystic fibrosis patients, it was noted that this bacterium ranked as the 5th most prevalent pathogen and frequently contributed to co-infections in the context of chronic Pseudomonas aeruginosa and Burkholderia cepacia complex infections (23). Similarly, S. maltophilia and P. aeruginosa were frequently identified as co-infecting organisms in a retrospective analysis of ventilator-associated pneumonia (VAP) caused by Achromobacter spp., where 84% of patients exhibited polymicrobial VAP (24). It is imperative to recognize that Achromobacter spp. can also behave as an opportunistic pathogen, playing a significant role in polymicrobial infections, especially in surgical site and abscess specimens.

In this study, the observed 28-day mortality rate was 11.7%, with mortality being higher in patients with monomicrobial infections. Given that these patients predominantly presented with bloodstream infections, it was hypothesized that the incidence of septic manifestations may have been elevated in this group. A retrospective analysis of 14 patients with Achromobacter spp. infections reported that those presenting with septic symptoms were bacteremic, and that the three patients who succumbed were also bacteremic and had presented with sepsis (4). Additionally, it was documented that mortality in patients with Achromobacter spp. infections following lung transplantation (27%) exceeded that of patients without such infections (12%) (6). When Achromobacter spp. was implicated as the etiologic agent in VAP, the mortality rate was reported to be 9% (24).

In a meta-analysis by Ronin et al. that evaluated surgical site infections caused by Achromobacter spp., it was reported that cases with mortality were mostly seen after complications and complicated surgery that led to mediastinitis, peritonitis, or endocarditis (22). Mortality rates were observed to fluctuate based on the clinical presentation and the site of infection; however, they remained elevated across all cases. Prompt identification of the infectious pathogen and its antimicrobial resistance, followed by the application of appropriate treatment, is crucial.

In this study, when comparing 45 bacteremic patients to those without bacteremia, it was observed that chronic conditions such as hypertension and coronary artery disease were more prevalent among bacteremic individuals, and the majority of these patients were managed in intensive care units. In instances of bacteremia outbreaks linked to contaminated disinfectants or pharmaceuticals, affected patients predominantly had chronic conditions, such as hematological malignancies or required hemodialysis (25, 26). In an observational study by Siddiqui et al. (4), it was reported that all bacteremic patients had either a hematological malignancy or an autoimmune disease. Although the difference in mortality was not statistically significant, a higher mortality rate was noted among bacteremic patients. Meropenem treatment rates were higher in patients with bacteremia, but mortality was still higher in this patient group. Considering the resistance rates, the fact that the mortality rate was higher despite the use of appropriate antibiotics indicates that other parameters such as patients' ICU severity scores and source control should also be taken into consideration.

In the present study, resistance rates to cefepime and ceftazidime were observed to exceed 50% in Achromobacter spp. isolates, whereas the lowest resistance rates were noted for piperacillin, tazobactam, and carbapenems. In the report by Marion-Sanchez et al., 59% of isolates from hospital-acquired infections exhibited fluoroquinolone resistance, while 38% were categorized as intermediate (2). In a 2014 analysis of antimicrobial susceptibility from isolates of 109 cystic fibrosis patients in France, the majority were found to have acquired fluoroquinolone resistance, with additional acquired resistance mechanisms reported for piperacillin, tazobactam, carbapenems, and ceftazidime-avibactam, particularly in A. xylosoxidans isolates (27). Carbapenem resistance was reported to exceed 50% in bacteremic patients (28).

When devising an empirical treatment regimen for infections caused by Achromobacter spp., factors such as the infection site, the severity of the disease, and regional resistance patterns must be carefully considered. Based on the resistance data from our region, particular caution should be exercised when empirically administering aminoglycosides, cephalosporins, and fluoroquinolones.