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Pseudomonas aeruginosa (P. aeruginosa) is one of the main microbes responsible for drug-resistant nosocomial infections¹⁾.　P. aeruginosa is naturally resistant to many antibiotics and has a remarkable capacity to acquire new resistance mechanisms, leading to increased therapeutic problems.　Multidrug resistant-P. aeruginosa (MDRP) is a strain that has acquired resistance to three classes of antibacterial agents:fluoroquinolones, carbapenems, and aminoglycosides²⁾.　Currently, the isolation rate of MDRP is reported to be 1–41%, and this varies greatly depending on the country and hospital environment^3-6).　Because of the limited choice of antibiotics, MDRP is often difficult to treat and is associated with high morbidity and mortality rates^7,8).

The process of acquiring antibiotic resistance is influenced by various factors, including the immune status of the host, length of hospital stay, prolonged use of antibiotics, and environment.　Moreover, there are potential differences in patient characteristics between upper- and lower- gastrointestinal surgery patients, such as esophageal cancer patients often suffering from postoperative pneumonia and rectal cancer patients suffering from urinary disturbance that require long-term placement of a urinary catheter, and these may lead to differences in the isolation of resistant bacteria.　In this study, we investigated the drug resistance status of P. aeruginosa, focusing on the isolation sites and type of gastrointestinal disease.

Study participants

The microbiology laboratory database of the National Defense Medical College Hospital in Tokorozawa, Japan, was searched to identify all clinical cultures positive for P. aeruginosa between 2015 and 2022.　P. aeruginosa was isolated from 324 patients and 891 sites in the gastrointestinal surgical ward, where upper and lower gastrointestinal surgeries were primarily performed.　Clinicopathologic features and susceptibility of P. aeruginosa to any antibiotics were evaluated in patients admitted to the division of upper gastrointestinal surgery (Upper-GI group, N = 97) and those admitted to the division of lower gastrointestinal surgery (Lower-GI group, N = 227).　In addition, we investigated the susceptibility of P. aeruginosa to any antibiotics based on the isolation site.

All subjects provided written informed consent for the inclusion of their data.　This study was conducted according to protocols approved by the National Defense Medical College Institutional Review Board (Permission number:4147).

Scores of susceptibilities to antibiotics

Susceptibility to antibiotics was determined by measuring the minimal inhibitory concentrations (MIC) and was scored based on the MIC, as shown in Table 1.　The MDRP score was defined as the sum of the imipenem (IPM), amikacin (AMK), and ciprofloxacin (CPFX) scores (minimum, 3 points; maximum,14 points).　The breakpoints were classified as susceptible (S), intermediate (I), and resistant (R) according to the recommendations of the Clinical and Laboratory Standards Institute⁹⁾.　When P. aeruginosa was detected multiple times, the maximum score or breakpoint for each antibiotic was used.

Statistical analysis

Continuous data were presented as mean ± standard deviation (SD).　Statistical analyses were performed using the Mann–Whitney U test, chi-square test, or Fisher’s exact test, as appropriate.　Statistical significance was set at p < 0.05.　All analyses were performed using JMP Pro 15 software (SAS Institute, Cary, NC, USA).

Table 1.

Breakpoints and susceptibility scores for each antibiotic

MIC, minimal inhibitory concentration

Table 2 shows the demographic characteristics and operative outcomes of the Upper -GI and Lower-GI groups.　The Upper-GI group had significantly older patients, predominantly male, and more patients admitted to intensive care than the Lower-GI group.　Cefazolin was frequently used as a prophylactic antibiotic in the Upper-GI group, whereas cefmetazole was frequently used in the Lower-GI group.　There were no significant differences in comorbidities, steroid use, length of hospital stay, or hospital death between the two groups; however, the number of patients with a previous hospitalization was significantly higher in the Upper-GI group than in the Lower-GI group.　Furthermore, the Upper-GI group had a higher percentage of patients requiring endotracheal intubation, central venous catheterization, and blood purification therapy than the Lower-GI group.　A higher percentage of P. aeruginosa was isolated from sputum in the Upper-GI group, whereas a higher percentage ofP. aeruginosa was isolated from urine in the Lower-GI group.

The Upper-GI group had more cases with an IPM score of 4 or 5 (i.e. cases with a breakpoint of R as resistance to IPM) than the Lower-GI group, although there were no differences in either AMK or CPFX scores.　The Upper-GI group had significantly higher MDRP scores than the Lower-GI group (Fig. 1).　In addition, the Upper-GI group had higher meropenem (MEPM), doripenem (DRPM), and cefozopran (CZOP) scores than the Lower-GI group (Table 3).

Next, we investigated the antibiotic resistance according to the isolation sites in the two groups (Table 4).　Among P. aeruginosa isolates from drain discharge, a significantly higher rate of resistance to IPM, AMK, CPFX, tazobactam/piperacillin (TAZ/PIPC), MEPM, DRPM, CZOP, and levofloxacin was observed in the Upper-GI group.　Similarly, among P. aeruginosa isolates from wounds, a significantly higher proportion was resistant to IPM, PIPC, TAZ/PIPC, ceftazidime, and CZOP in the Upper-GI group.　However, there was no difference between the two groups in the drug resistance of P. aeruginosa isolated from urine, sputum, blood, and ascites.　P. aeruginosa isolated from sputum was more likely to show resistance to IPM (P=0.07) than that isolated from other sites (Fig. 2) and was more likely to have higher MDRP scores than that isolated from other sites, specifically there were significant differences compared to that from wound and ascites (Fig. 3).

Table 2.

Demographics and operative outcomes in the Upper-GI and Lower-GI groups

GI, gastrointestinal; IBD, inflammatory bowel disease; CEZ, cefazolin; CMZ, cefmetazole

Fig. 1.

Susceptibility to three classes of antibiotics and MDRP scores in the Upper-GI and Lower-GI groups

The Upper-GI group had more cases with an IPM score of 4 or 5 (i.e. cases with a breakpoint of R as resistance to IPM) than the Lower-GI group, although there were no differences in either AMK or CPFX scores. The Upper-GI group had significantly higher MDRP scores than the Lower-GI group.

GI, gastrointestinal; IPM, imipenem; AMK, amikacin; CPFX, ciprofloxacin; MDRP, multidrug resistant-Pseudomonas aeruginosa

Table 3.

Breakpoints for antibiotics in the Upper-GI and Lower-GI groups

GI, gastrointestinal; PIPC, piperacillin; TAZ/PIPC, tazobactam/piperacillin; MEPM, meropenem; DRPM, doripenem; CAZ, ceftazidime; CZOP, cefozopran; LVFX, levofloxacin; NA, not assigned

Table 4.

Breakpoints for each antibiotic according to the isolation sites

GI, gastrointestinal; IPM, imipenem; AMK, amikacin; CPFX, ciprofloxacin; PIPC, piperacillin; TAZ/PIPC, tazobactam/piperacillin; MEPM, meropenem; DRPM, doripenem; CAZ, ceftazidime; CZOP, cefozopran; LVFX, levofloxacin; NA, not assigned; S, susceptible; I, intermediate; R, resistant

Fig. 2.

Breakpoints for IPM, AMK, and CPFX according to the isolation sites.

Pseudomonas aeruginosa isolated from sputum was more likely to show drug resistance to IPM and CPFX than those isolated from other sites.

IPM, imipenem; AMK, amikacin; CPFX, ciprofloxacin

Fig. 3.

MDRP score according to the isolation sites

Pseudomonas aeruginosaisolated from sputum more likely had higher MDRP scores than those isolated from other sites.

*P< 0.05 versus wound and ascites

MDRP, multidrug resistant-Pseudomonas aeruginosa

In this study, we demonstrated that there were significant differences in the drug resistance of P. aeruginosa, depending on the site of isolation and gastrointestinal disease type.　In the Upper-GI group, resistance to PIPC, TAZ/PIPC, MEPM, DRPM, and CZOP as well as to the three classes of antibiotics used to define MDRP, was observed.

Endotracheal intubation, central venous catheter placement, and blood purification therapy were performed more frequently in the Upper-GI group than in the Lower-GI group, suggesting that the Upper-GI group required intensive care and included more severely ill patients compared with the Lower-GI group.　Resistance is more frequent in units for the management of patients with burns and cystic fibrosis and in intensive care units^6,10,11).　In addition, Palacios-Baena et al.　reported in a systematic review that the Acute Physiology and Chronic Health Evaluation II score is a risk factor for carbapenem-resistant Gram-negative bacterial infections¹²⁾.　Therefore, it has been suggested that patients with severe diseases are more likely to develop drug resistance to P. aeruginosa.

There were significant differences in the susceptibility of P. aeruginosa isolated from drains and wounds between the two groups; however, no differences were observed in the susceptibility of P. aeruginosa isolated from urine, sputum, blood, or ascites.　In this regard, the reason for the significantly higher IPM and MDRP scores in the Upper-GI group is considered to be that the frequency of isolation from sputum was higher in the Upper-GI group than in the Lower-GI group.　More than half of the patients in the Upper-GI group were diagnosed with esophageal cancer.　It is well-known that respiratory complications often occur after surgery for esophageal cancer, and the frequent isolation of P. aeruginosa from sputum is reasonable¹³⁾.　Livermore reported that P. aeruginosa isolated from the sputum of patients with cystic fibrosis showed higher resistance to anti-pseudomonal antibiotics than that isolated from other sites in inpatients, intensive care unit patients, and outpatients in the United Kingdom¹⁴⁾.　Drug resistance is common among organisms isolated from the respiratory tract, particularly from patients in intensive care units and teaching hospitals^8,15).　These results suggested that P. aeruginosa isolates from sputum may have higher drug resistance than those isolated from other sites.　P. aeruginosa was more frequently isolated in the urine in the Lower-GI group because rectal cancer patients often suffer from urinary disturbance and require long-term placement of a urinary catheter, although there was no difference in the rate of urinary catheter placement between the two groups.

This study had several limitations.　First, this study was conducted in a retrospective nature and the data used in this study were obtained from the microbiology laboratory database, which includes both colonization and infection data.　In addition, this study could not distinguish between community-acquired and hospital-acquired infections and the results should be interpreted with caution.　Second, patients with postoperative infectious complications of gastrointestinal cancer and emergently hospitalized patients requiring intensive care were included in this study; thus, the reasons for hospitalization were not uniform.

In conclusion, physicians should be aware, especially in the case of empirical treatment, that there were significant differences in the drug resistance of P. aeruginosa isolated from different sites and types of gastrointestinal tract diseases.　Antimicrobial agents should be appropriately administered in the gastrointestinal ward under careful distinction between colonization and pathogen.

We would like to thank Editage (www.editage.com) for English language editing.

The authors have declared no conflicts of interest.

All subjects provided written informed consent for the inclusion of their data.　This study was conducted according to protocols approved by the National Defense Medical College Institutional Review Board (Permission number:4776).