A retrospective study of Aeromonas hydrophila infections at a university tertiary hospital in Saudi Arabia

Aeromonas hydrophila risk factors, clinical disease, and factors associated with mortality were studied in a large hospital in Saudi Arabia. This is the first study from this region about this particular species. The Pitt bacteremia score, Charlson weighted comorbidity index, INR, and the number of comorbidity factors were all found to be associated with 30-day mortality due to Aeromonas infection. Of these risk factors, the number of comorbidity factors had the best predictive value for 30-day mortality due to Aeromonas infection.

In general, patients accumulate more comorbidities with advanced age, thus increasing the risk of 30-day mortality. In this retrospective study, each patient had at least one comorbidity. In a prospective study of 78 individuals that tested positive for Aeromonas species in France, the majority of individuals (61.5%) did not have any comorbidities [7]. Most of the patients in the current study had renal impairment, followed by hypertension, chronic liver disease, and diabetes. These comorbidities are different from a larger study in Taiwan, where they found chronic liver disease (54%) and malignancy (22%) as the most common comorbidities associated with Aeromonas bacteremia [13] and the French study, where malignancy (19.2%) and immunosuppression (14.1%) were the most common comorbidities [7]. These differences in comorbidities may partly be explained by the fact that in the French study, only 35.7% of cultures contained A. hydrophila [7], and in the Taiwanese study, only 58% of cultures contained A. hydrophila [13], as the various Aeromonas species proved to have different disease presentations [7]. A. hydrophilia was mostly (76%, 19/25) found in wound and skin soft tissue infections, while for instance A. veronii and A. caviae were found mostly in other sites and only in 43% (12/28) and 20% (3/15) respectively in wound and skin soft tissue infections. These differences suggest the disease presentations, including the comorbidities, cannot easily be compared between the patients from the different studies as they did not all have the same Aeromonas infections. In addition, there may be genetic and cultural differences between the patients in these countries that explain these differences.

In terms of the clinical picture, the most common sign encountered in the current study was fever secondary to central line infection, and the most common symptom was abdominal pain, followed by dyspnea. Only 12% of the patients had diarrhoea, in contrast to studies where diarrhoea was usually named as the most common symptom (although percentages are not given) in adults and children [1, 8]. This diarrhoea is self-limiting and sometimes associated with chronic colitis [1, 14]. In Spain, Aeromonas was found to be the fourth most common cause of gastroenteritis among microbiological causes of gastroenteritis (although that did not tell us how many of the Aeromonas cases had gastroenteritis) [15]. In the French study, only 19% of patients had gastroenteritis [7], while in an earlier Taiwanese study only 5% had diarrhoea as presenting symptom [16]. Together these results suggest that diarrhoea is not as common in Aeromonas infection as previously thought. Further studies are needed in larger numbers of patients to determine whether this is indeed the case.

In the patients, 75% of the invasive infections associated with wounds were hospital-acquired, nosocomial infections rather than community-acquired infections. In contrast, in a study of hospitalised patients in India, only 19% of the infections were hospital-acquired [17]. In a study in France about half of the wound and soft tissue infections were due to freshwater exposure [7]. It can be speculated that in Saudi Arabia the lack of fresh open water (such as lakes and rivers) reduces the chances of developing an environment-acquired A. hydrophilia infection.

The 30-day mortality was, at 20.8%, not high in the patients in the current study compared to other studies, although not easy to compare as different time frames were used: For instance, in the study in Taiwan, 14-day mortality was 32% [13], and in a study in Spain 1-year mortality was 26.5% [18]. Overall, the reported mortalities ranged between 25% and 46% in cases with bacteremia and were about 50% in cases with pneumonia [2, 4, 16, 19,20,21,22]. The low mortality rate in the current study can be attributed to the fact that most of the cases had skin and soft tissue infections, which has a relatively good prognosis, while none of them had necrotizing fasciitis, and few cases had pneumonia (12%), which are usually associated with high mortality.

The factors associated with 30-day mortality in this study were high Pitt bacteremia scores, a high Charlson weighted comorbidity index, high INR, and a large number of comorbidity factors. In the study in Spain, age, in-hospital patient, ICU stay, extraintestinal presentation, malignancy, and antimicrobial treatment were associated with increased mortality [18]. In the study in Taiwan, the strongest association was found with initial serum creatinine, the number of positive blood cultures, and the severity score [13]. Comparisons between the factors associated with mortality were hampered by a difference in percentage of patients with A. hydrophila, as this was 100% in the current study, 58% in the Taiwanese study, and unknown in the Spanish study. In addition, it was previously found that the various Aeromonas species have different clinical presentations [7], which may also affect factors associated with mortality.

Several studies reported that most patients developed Aeromonas infection following trauma or environmental exposures, as Aeromonas is found in the environment and soil [23,24,25]. In the current study, none of the patients with skin and soft tissue infections had a history of trauma, and their infections were considered secondary to underlying comorbidities. A similar result was also reported in a study in which less than 3% of patients had skin and soft tissue infections due to surgical or traumatic wound infection [18].

Antibiotic susceptibility testing showed 0% resistance to gentamicin, cefepime, and ciprofloxacin in this study. In contrast, 83.3% of specimens were resistant to ceftazidime, 75% to ceftriaxone, and 62.5% to meropenem. In an extensive review, Aeromonas was reported to be uniformly resistant to ampicillin, penicillin, and cefazolin, and was reported to have variable susceptibility to piperacillin-tazobactam as Aeromonas can produce β-lactamases including Ambler class D penicillinases, class C cephalosporinases, and TEM family extended spectrum β-lactamases [1]. We found zero resistance to gentamicin, which is in line with the observation that aminoglycosides (e.g., gentamicin) are usually active agents against Aeromonas [26]. Quinolones (e.g., ciprofloxacin) were also reported to work very well for Aeromonas species as resistance against quinolones is uncommon [27], which we confirmed in this study (0% resistance). Resistance to meropenem was low at 7% in Korea [20], whereas it was much higher in this study (62.5%). In the same study, resistance to ceftriaxone and piperacillin-tazobactam was 15.5% which was very different from what we found in the current study as both ceftriaxone resistance and piperacillin-tazobactam resistance were high at respectively 75% and 58.3% [20]. In Spain, similar results of high susceptibility to both cefepime and gentamicin were found [18], matching the results in the current study. Apparently, the resistance pattern of Aeromonas in Saudi Arabia is different from other regions. We speculate that the resistance patterns may be different between the regions due to a difference in antibiotic prescription and antimicrobial stewardship, causing the resistance to rise in some regions in comparison to others. Comparing genomic sequences of the strains from different countries may answer this question. When Aeromonas infection is suspected, treatment with a quinolone along with another broad-spectrum antibiotic, such as piperacillin/tazobactam or meropenem, can be started until the culture and susceptibility results are known.

The current study had several limitations. Firstly, the small number of patients. As Aeromonas infection is very rare, and only cases were included that had invasive disease while any Aeromonas-positive cases that appeared to be due to colonization rather than a true infection were excluded, a small number of patients was analysed. This made it difficult to do meaningful statistical analyses. Secondly, no genomic testing was performed to assess the molecular basis of resistance. Genomic testing may have given a better picture of common resistant mechanisms in Saudi Arabia. And thirdly, the study was performed in a single hospital, so the results cannot be generalised to other hospitals. A future large, prospective, multi-center study could identify larger numbers of patients, thus resulting in more robust data.

A strength of the study was that it was the first study of its kind in Saudi Arabia, and performed at a large University teaching hospital. So far, very little was known about Aeromonas infections and their clinical implications in Saudi Arabia.