Drug resistance, including antimicrobial resistance, is a global issue, because it affects people all over the world, particularly people in developing countries. Based on a sample of ICU patients in a major hospital in Vietnam, we have shown that approximately 95% of ventilator-associated pneumonia patients were resistant to antibiotic drugs. More disturbingly, ~85% (n = 139) were multiple-drug resistant. These results deserve some further elaboration.
In this study, we found that the distribution of pathogens was different from previous studies in developing and developed countries. In most Asian countries, common pathogens isolated from ICU patients were P. aeruginosa, Klebsiella spp., E. coli, Enterococcus, and Staphylococcus aureus [7]. Moreover, the Canadian National Intensive Care Unit study found that P. aeruginosa, Staphylococcus aureus, Haemophilus influenzae, Enterococcus spp., Staphylococcus pneumoniae, and K. pneumoniae are the most common isolates [8]. However, in our study, the most common pathogen was Acinetobacter, followed by Klebsiella and P. aeruginosa. Both Acinetobacter and P. aeruginosa demonstrated multidrug resistance to several antibiotics.
A striking finding from this study was the degree of drug resistance among key pathogens. We found a very high rate of resistance (>70%) among Acinetobacter isolates to most antibiotics, except cefoperazone-sulbactam (4.3%) and colistin (1.5%). Among Klebsiella isolates, low resistance was found for amikacin (5.1%), but high for cefoperazone, ceftazidime, ceftriaxone, cefepime, and levofloxacin. Resistance to meropenem, imipenem, gentamycin, ciprofloxacin and levofloxacin among P. aeruginosa was consistently over 80%. This is probably due to the extensive use of third generation of cephalosporins and quinolone antibiotics in ICU patients.
Previous studies found that the opportunistic pathogens Acinetobacter spp., mainly A. baumannii, are commonly found in ICUs. Our study also found that Acinetobacter was the most common pathogen in ICU patients, and this finding has significant clinical implications. This Acinetobacter spp. has shown a remarkable resistance to many antibiotic classes. Acinetobacter infection is also associated with a high risk of mortality, as there are limited treatment options for this infection. In our study, apart from colistin, Acinetobacter was resistant to virtually all antibiotics, including imipenem (93%), meropenem (90%), ertapenem (100%), ceftriaxone (95%), ceftazidime (93%), cefepime (94%), piperacillin (95%), and ciprofloxacin (95%). Therefore, Acinetobacter is increasingly recognized as an important cause of hospital-acquired infection [9, 10], and our finding confirms the significance of this species as a leading cause of MDR infection in critically ill patients with ventilator-associated pneumonia.
Klebsiella is considered an opportunistic pathogen, and Klebsiella infection is commonly found in hospitalized patients with conditions such as diabetes and chronic pulmonary obstruction [11]. In human, K. pneumoniae, the most important species of the genus, was identified as a pulmonary pathogen more than 100 years ago. While K. pneumoniae has been declining in the United States [12], it is still common in China [13], particularly in ventilator-associated pneumonia patients [14]. In this study, we found that the pathogen accounted for ~22% of all infected patients, and the pathogen is also common in patients with diabetes and pulmonary disorders. In Southeast Asia, among K. pneumoniae isolates, the resistance rate to ciprofloxacin was 62% in Philippines, 29% in Thailand, and 22% in Singapore [15]. In our study, the rate of resistance to ciprofloxacin was 53%. It is not clear why there exists geographic differences in the rates of resistance between countries, but the interaction between environmental reservoir and host variables may be a contributory factor.
In this study P. aeruginosa was the third most common pathogen in ventilator-associated pneumonia. Previous studies have also observed that P. aeruginosa is a prominent cause of pneumonia in hospital setting in Southeast Asia. In previous studies, ciprofloxacin resistance rates among Pseudomonas spp. were over 10% in Malaysia and Singapore [15], which was much lower than our study’s rate (80%). Although the infection may be due to reservoirs within the hospital or ICU environment, selective antimicrobial pressure and compromise of the respiratory tract can also be a risk factor.
Our findings have important clinical implications in the treatment and management of ICU patients, particularly those with ventilator-associated pneumonia. First, clinicians should realize that there is a high possibility that ventilator-associated pneumonia patients are infected with the three common pathogens, and that multiple drug resistance is a reality. Second, the high rate of multidrug resistance observed in this study is a serious concern in the management of ICU patients. It calls for a more systematic approach to reduce antibiotic resistance rates, and minimizing the use of broad-spectrum antibiotics. Third, in the presence of multidrug resistance, the development of rapid diagnostic test for prompt targeted therapy is an important priority. There is also a need for implementing a drug monitoring system that optimizes drug administration and enable a more personalized approach to treatment.
The present study’s findings nevertheless should be interpreted within context of strengths and weaknesses. The study was conducted in a well characterized cohort of patients, who had been thoroughly followed. We have been able to analyze a whole spectrum of pathogens and antibiotic treatments, which allow a relatively comprehensive documentation of antimicrobial resistance in ICU patients. However, we did not have the capacity to conduct a 16S–rRNA gene sequence analysis to identify bacterial species, and this is a significant weakness of the study. Moreover, we did not undertake a phenotypic test that would provide an insight into the mechanism of drug resistance. The study was based on a tertiary hospital and the data were limited to ICU patients; thus the findings may not represent the community acquired infection in Vietnam. The sample size for the study was modest, and did not have adequate power to detect smaller effect sizes or rare incidence. We did not ascertain the specific causes of infection and comorbidities. We also did not ascertain all aspects of care that may have resulted in the prescription of inappropriate antibiotics in our patients.