Molecular characterization of Clinical carbapenem-resistant Acinetobacter baumannii isolates from two tertiary care hospitals in Indonesia
Heriyannis Homenta1,2*, Julyadharma3, Yulia Rosa Saharman4, Kuntaman Kuntaman5,
Hani Susianti6, Dewi Santosaningsih7, Noorhamdani7
1Doctoral Program in Medical Science, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia.
2Department of Clinical Microbiology, Faculty of Medicine, Sam Ratulangi University, Manado, Indonesia.
3Laboratory of Clinical Microbiology, Prof. dr. R. D. Kandou Hospital, Manado, Indonesia.
4Department of Clinical Microbiology, Faculty of Medicine,
Universitas Indonesia/dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia.
5Department of Clinical Microbiology, Faculty of Medicine,
Airlangga University/dr. Soetomo Hospital, Surabaya, Indonesia.
6Department of Clinical Pathology, Faculty of Medicine,
Universitas Brawijaya/dr. Saiful Anwar Hospital, Malang, Indonesia.
7Department of Clinical Microbiology, Faculty of Medicine,
Universitas Brawijaya/dr. Saiful Anwar Hospital, Malang, Indonesia.
*Corresponding Author E-mail: herihomenta@unsrat.ac.id
ABSTRACT:
Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) is an important pathogenic bacterium that can cause nosocomial infection in hospitalized patients with various manifestations. The purposes of this recent study were to determine the prevalence, antimicrobial susceptibility profiles, carbapenemase-producing phenotypic and genotypic of CRAB in two tertiary care hospitals in Indonesia. Methods: A. baumannii isolates collected from patient’s clinical cultures in two tertiary care hospitals in Malang and Manado were included. Identifications of meropenem-resistant A. baumannii isolates with the vitek2® system results, followed by a sensitivity test using 10 µg imipenem antibiotic disc according to CLSI guidelines to fulfill the criteria as CRAB isolates. We assessed carbapenemase-production using mCIM and eCIM, and determined the presence of blaKPC, blaNDM, blaOXA-23 carbapenemase resistance genes using simplex PCR. Results: 73 CRAB were collected from hospitalized patients, of which 30 CRAB from Manado and 43 CRAB from Malang. The largest number of samples came from sputum and indicates that XDR has also occurred in all CRAB isolates. Carbapenemase-production test using mCIM obtained positive results on 29 samples (96.7%) and 42 samples (97.7%) in Manado and Malang, respectively. The eCIM showed metallo-β-lactamase was dominant in two tertiary care hospitals. The prevalence of carbapenemase resistance genes was obtained blaOXA-23 and blaNDM ranged between 60% - 90.7% and 3.3% - 4.6%, respectively. blaKPC gene was not detected. Conclusions: We showed that CRAB isolates positive result of carbapenemase-production and carbapenemase resistance genes of blaOXA-23 seem to be dominant in two tertiary care hospitals in Malang and Manado, Indonesia. A national prevention and surveillance system should be prepared to reduce and limiting transmission of CRAB isolates.
KEYWORDS: Acinetobacter baumannii, carbapenem resistance genes, carbapenemase, mCIM.
INTRODUCTION:
Acinetobacter baumannii (A. baumannii) is a Gram-negative bacteria causing nosocomial infections and has become a globally emerged multidrug-resistant bacteria, especially carbapenem-resistant in the last decade.1,2 A survey in USA hospitals found clinical A. baumannii isolates predominantly from respiratory tract (57.6%), followed by bloodstream (23.9%), skin or wound (9.1%), and urinary tract (3.3%).3 Research in Egypt obtained the results of A. baumannii bacterial infection by respiratory tract (24.1%).4 Study in Jakarta showed that the infection of A. baumannii in 5 neonates (17.8%).5 CDC reported Acinetobacter sp. nosocomial infections were about 8.500 cases, as many as 700 deaths were related with antibiotic resistance.6
The main mechanism of Carbapenem-resistant A. baumannii (CRAB) is production of β-lactamase, whereas carbapenemases hydrolyze carbapenem antibiotic.7,8,9 The other mechanism is porin and outer membrane protein (OMP) mutation and over-expression of efflux pump.2,10,11 Additionally, the length of stay in the intensive care unit (ICU) and surgical ward was related to prolonged use of antibiotics, such as carbapenem antibiotics.12,13 Research in Los Angeles, California obtained the results of GES and OXA-23,14 Iraq were discovered AmpC, OXA-23 and OXA-235,15 Egypt showed that KPC, NDM and OXA-23,16 as well as Jakarta and Surabaya, Indonesia reported NDM and OXA-23, but not yet representing all regions of Indonesia. Molecular antibiotic resistance showed different genetic spread in each study site.16,17 Therefore, the CRAB’s phenotypic and genotypic features need to be investigated to track the global dissemination, understand the molecular epidemiology and optimize antibiotic use.16,18
Data on phenotypic and genotypic of CRAB in Malang and Manado, Indonesia is scarce. Different of climate, environment, equipment, sterilization, disease, and treatments in different regions have led to diverse of genes resistance of A. baumannii.17,19 Therefore, it is important to figure out the clinical characteristics and drug resistance profiles of A. baumannii in a certain area during certain periods. The present study aimed to explore and determine the prevalence, antimicrobial susceptibility profiles, phenotypic and genotypic of CRAB in dr. Saiful Anwar Hospital, Malang and Prof. dr. R. D. Kandou Hospital, Manado, Indonesia.
METHODS:
Setting and Study design:
The present prospective observational study was performed in two tertiary care hospitals in Malang, East Java and Manado, North Sulawesi, Indonesia (Figure 1). The study was performed from March - August 2019 in dr. Saiful Anwar Hospital, Malang, East Java, with 908 inpatient beds, and from June - November 2019 in Prof. dr. R. D. Kandou Hospital, Manado, North Sulawesi, with 838 inpatient beds and 211 action beds with an average occupancy rate of 79.8%.20 Sample culture collected by Clinical Microbiology Laboratory in two tertiary care hospitals was derived from a variety of wards are ICU, Neonatal intensive care unit (NICU), Cardiovascular intensive care unit (CVICU), medical, and surgical in hospital.
The ethical committee approved this study in health research of dr. Saiful Anwar Hospital, Malang (No. 400/059/K.3/302/2019), and Prof. dr. R. D. Kandou Hospital, Manado (No. 054/EC-KEPK/IV/2019).
Figure 1. Map of Indonesia depicting the two tertiary care hospital in Malang and Manado.
Note: dr. Saiful Anwar hospital, Malang and Prof. dr. R. D. Kandou hospital, Manado (squares) and the capital city Jakarta is also indicated (cicle).
Bacterial isolates:
A. baumannii strains were isolated from blood, urine, sputum, and pus by clinically indicated culture in two tertiary care hospitals in Malang and Manado. Isolation of A. baumannii were performed according to the routine diagnostic procedures, followed by identification and antibiotic susceptibility test using the VITEK2® system (bioMérieux, Lyon, France).21,22
Meropenem-resistant A. baumannii was continued by a disc diffusion test with 10 µg imipenem antibiotics disc according to CLSI guideline to fulfill as CRAB isolates.23,24 Strains were stored in duplicate inoculated into a trypticase soy broth with 10% glycerin and stored at -80°C.
Modified Carbapenem Inactivation Method (mCIM) and EDTA-Carbapenem Inactivation Method (eCIM):
Identification of carbapenemase-producing A. baumannii and production of a metallo-β-lactamase using mCIM and eCIM, respectively.24,25 CRAB bacteria stock in tryptic soy broth with 10% glycerol stored at -80°C were subcultured on 5% sheep blood agar and incubated at 35°C ± 2°C for 18 to 24 h. Then, Growth of CRAB from the second subculture was used to set up the mCIM and eCIM assays as previously described.25,26
DNA extraction and carbapenemase gene detection:
According to the manufacturer’s instructions, extraction of CRAB DNA is through the steps of cell lysis and boiling using the GeneAll® ExgeneTM. Detection of Ambler class A (blaKPC), Ambler class B (blaNDM), and Ambler class D (blaOXA-23) resistance genes using PCR was performed as previously described.14
Statistical analysis:
Chi-square (x2) test was used to compare the antibiotic resistance level between isolates of A. baumannii in two tertiary care hospitals using the statistical software packages IBM SPSS version 23. A p-value less than 0.05 was considered significant.
RESULTS:
A total 73 CRAB were obtained from dr. Saiful Anwar hospital, Malang (n = 43) and Prof. dr. R. D. Kandou hospital, Manado (n = 30). The majority of CRAB were found from sputum (57.5%), followed by pus (16.5%), blood (15.1%), and urine (10.9%) (Table 1).
Table 1. Prevalence and sources of CRAB in two tertiary care hospitals in Indonesia
|
Hospital |
Sample |
Number of CRAB Isolates |
Percentage (%) |
|
dr. Saiful Anwar hospital, Malang |
Blood Urine Sputum Pus Total |
9 5 28 1 43 |
20.9 11.6 65.2 2.3 100 |
|
|
|
|
|
|
Prof. dr. R. D. Kandou hospital, Manado |
Blood Urine Sputum Pus Total |
2 3 14 11 30 |
6.6 10 46.7 36.7 100 |
Table. 2 shows the resistance rate of CRAB in two tertiary care hospitals in Indonesia. Isolates of CRAB were significant resistant (100%) to ampicillin/sulbactam, piperacillin/tazobactam, cefazolin, ceftazidime, ceftriaxone, cefepime, meropenem, imipenem, gentamicin, and ciprofloxacin. The CRAB was susceptible to trimethoprim/sulfamethoxazole 34.9% - 43.3%, amikacin 37.2% - 53.3%, and tigecycline 62.8% - 96.7%.
Carbapenemase-production test on 30 samples of the CRAB bacteria in Prof. dr. R. D. Kandou Hospital, Manado using mCIM (Figure 2: 2A and 2B) obtained positive results on 29 samples (96.7%), and one sample (3.3%) showed negative results or no carbapenemase production. Furthermore, followed by the eCIM test, 28 samples (93.3%) showed positive results for metallo-β-lactamase, and two samples (6.7%) showed positive results for serine carbapenemase on CRAB bacteria (Table. 3).
The results of the carbapenemase production test using mCIM on 43 samples of CRAB in dr. Saiful Anwar General Hospital, Malang (Figure 2: 1A and 1B) showed positive results in 42 samples (97.7%), and one sample (2.3%) showed negative results or no carbapenemase production. Then, continued with the eCIM test, 39 samples (90.7%) showed positive results for metallo-β-lactamase, and two samples (4.6%) showed positive results for serine carbapenemase in CRAB bacteria (Table. 3).
Table 2. Results of antimicrobial susceptibility in two tertiary care hospitals in Indonesia
|
Antibiotics* |
dr. Saiful Anwar hospital, Malang (n=43) |
Prof. dr. R. D. Kandou hospital, Manado (n=30) |
p-value
|
|
Susceptible Number of strains (%) |
Susceptible Number of strains (%) |
||
|
A/S |
0 |
0 |
ND |
|
P/T |
0 |
0 |
ND |
|
CFZ |
0 |
0 |
ND |
|
CAZ |
0 |
0 |
ND |
|
CRO |
0 |
0 |
ND |
|
CPM |
0 |
0 |
ND |
|
MEM |
0 |
0 |
ND |
|
IPM |
0 |
0 |
ND |
|
GEN |
0 |
1 (3.3) |
0.228 |
|
CIP |
0 |
2 (6.7) |
0.086 |
|
SXT |
15 (34.9) |
13 (43.3) |
0.465 |
|
AMK |
16 (37.2) |
16 (53.3) |
0.172 |
|
TGC |
27 (62.8) |
29 (96.7) |
0.001 |
ND, not determined because of one hundred percent of resistant case.
*abbreviations of antibiotics tested: A/S, Ampicillin/Sulbactam; P/T, Piperacillin/Tazobactam; CFZ, Cefazolin; CAZ, Ceftazidime; CRO, Ceftriaxone; CPM, Cefepime; MEM, Meropenem; IPM, Imipenem; GEN, Gentamicin; CIP, Ciprofloxacin; SXT, Trimethoprim/Sulfamethoxazole; AMK, Amikacin; TGC, Tigecycline.
Figure 2. Result of Carbapenemase Production Test.
Note: 1A. modified Carbapenem Inactivation Method, 1B. EDTA-Carbapenem Inactivation Method on CRAB isolates in Prof. dr. R. D. Kandou Hospital, Manado.
2A. modified Carbapenem Inactivation Method, 2B. EDTA-Carbapenem Inactivation Method on CRAB isolates in dr. Saiful Anwar Hospital, Malang.
Study to determine carbapenemase-production and identification resistance genes, that is blaKPC, blaNDM, blaOXA-23 in the CRAB isolates from inpatients in two tertiary care hospitals, where the results are shown in the Table. 3.
In dr. Saiful Anwar Hospital, Malang, the results of the identification of blaNDM resistance genes using the PCR simplex method (Table. 3) obtained positive results in two samples (3.3%) of CRAB, namely the samples of MLG-13 and MLG-16, as well as the positive results on the mCIM and eCIM tests on CRAB bacteria. Identification of the blaOXA-23 resistance gene using the PCR simplex method (Table. 3) were positive in 39 samples (90.7%), and the positive results on the mCIM and eCIM tests for CRAB bacteria. Also, it was found that 4 samples (9.3%) did not have carbapenemase resistance genes of blaKPC, blaNDM, blaOXA-23 of CRAB bacteria.
In Prof. dr. R. D. Kandou Hospital, Manado, the results of the identification of blaNDM resistance genes using the PCR simplex method (Table. 3) obtained positive results in one sample (4.7%), namely the sample of MDO-2, and also the positive results on the mCIM and eCIM tests on CRAB bacteria. Identification of the blaOXA-23 resistance gene using the PCR simplex method (Table. 3) was obtained positive results on 18 samples (60%) and following positive results in the mCIM and eCIM tests for CRAB bacteria. Also, 11 samples (36.7%) were found to have no carbapenemase resistance genes of blaKPC, blaNDM, blaOXA-23 of CRAB bacteria.
Table 3. Antibiotic Resistance Genes Results and Carbapenemase-Production of CRAB in two tertiary care hospitals Malang and Manado
|
Clinical specimen |
Total specimen |
Carbapenemase Resistance Genes |
mCIM |
|
eCIM |
||||
|
blaKPC |
blaNDM |
blaOXA-23 |
Positive |
Negative |
Metallo-β-lactamase |
Serine-β-lactamase |
|||
|
dr. Saiful Anwar hospital, Malang |
Blood |
9 |
0 |
0 |
7 (77.8%)a |
9 (100%) |
- |
9 (100%) |
- |
|
Urine |
5 |
0 |
0 |
5 (100%) |
5 (100%) |
- |
4 (80%) |
- |
|
|
Sputum |
28 |
0 |
2 (7.1%) |
26 (92.9%) |
27 (96.4%) |
1 (3.6%) |
25 (89.3%) |
2 (7.1%) |
|
|
Pus |
1 |
0 |
0 |
1 (100%) |
1 (100%) |
- |
1 (100%) |
- |
|
|
Prof. dr. R. D. Kandou hospital, Manado |
Blood |
2 |
0 |
0 |
2 (100%) |
2 (100%) |
- |
2 (100%) |
- |
|
Urine |
3 |
0 |
0 |
2 (66.7%)b |
3 (100%) |
- |
3 (100%) |
- |
|
|
Sputum |
14 |
0 |
0 |
8 (57.1%)c |
13 (92.9%) |
1 (7.1%) |
14 (100%) |
- |
|
|
Pus |
11 |
0 |
1 (9%) |
6 (54.5%)d |
11 (100%) |
- |
9 (81.8%) |
2 (18.2%) |
|
KPC: K. pneumoniae carbapenemase, NDM: New Delhi metallo-β-lactamase, OXA-23: Oxacillinase-23, mCIM: modified Carbapenem Inactivation Method, eCIM; EDTA-Carbapenem Inhibitor Method.
b, one CRAB isolate from urine in Prof. dr. R. D. Kandou Hospital Manado was not detected by the three of carbapenemase resistance genes.
c, six CRAB isolates from sputum in Prof. dr. R. D. Kandou Hospital Manado were not detected by the three of carbapenemase resistance genes.
d, four CRAB isolates from pus in Prof. dr. R. D. Kandou Hospital Manado were not detected by the three of carbapenemase resistance genes.
DISCUSSION:
This study is the first study to explore and determine the molecular epidemiology of CRAB, which was conducted in two tertiary care hospitals in Indonesia, namely dr. Saiful Anwar Hospital, Malang, East Java and Prof. dr. R. D. Kandou Hospital, Manado, North Sulawesi.
This study showed that majority of the CRAB obtained from both hospitals were found from sputum (46.7% - 65.2%), caused by many samples collected from patients admitted to the ICU with endotracheal tubes, and we suspected that the infection had spread.27,28 The results of majority CRAB from sputum were consistent with research in Guangzhou, China.29 The results of the isolation of CRAB bacteria from urine in two tertiary care hospitals were comparable to research conducted at dr. Soetomo Hospital, Surabaya with a 10.7% incidence of A. baumannii bacterial infection with carbapenem resistance from urine.21
The results of the research on the antibiotic sensitivity test for A. baumannii to carbapenem in two tertiary care hospitals in Malang and Manado shows the category of extensively drug resistant (XDR) antibiotic resistance, this result is different from the results of studies that are still multidrug resistant (MDR) in Jakarta and Surabaya,21,22 and also in Egypt,16,30 Taiwan,31 Nepal,32 and Los Angeles.14 This suggests that there has been an increased incidence of antibiotic resistance33,34 and a widespread of carbapenemase resistance genes from CRAB bacteria widely, including in two tertiary care hospitals, so that it becomes a warning to all medical personnel in every hospital in Indonesia to be vigilant and wise in the use of antibiotics used for inpatients at the hospital.
In two tertiary care hospitals, the CRAB still sensitive around 34.9% - 43.3% to trimethoprim-sulfamethoxazole antibiotics, sensitive around 37.2% - 53.3% to amikacin antibiotics, and sensitive around 62.8% - 96.7% to tigecycline antibiotics. This result need further research on the three antibiotics against bacterial infection of CRAB for more efficient treatment strategies. The results of this study were the same as those found in dr. Soetomo Hospital, Surabaya,21 Nepal,32 and Los Angeles.14
Research on carbapenemase-production test using mCIM in dr. Saiful Anwar Hospital, Malang showed 42 samples (97.7%) carbapenemase, and one sample (2.3%) of negative carbapenemase-production. In Prof. dr. R. D. Kandou Hospital, Manado obtained 29 samples (96.7%) that produced carbapenemase, and one sample (3.3%) of negative carbapenemase production, but in 11 specimens, there were no carbapenemase resistance genes. Negative carbapenemase-production caused by A. baumannii has outer membrane permeability of intrinsic low-degree,11 and OXA-type CHDL (blaOXA-23), the most general types of carbapenemase produced by A. baumannii, but not efficient and reduced carbapenemases, in contrast to other class A serine (blaKPC) and class B metallo-β-lactamases (blaNDM). The CRAB strains can also be caused by the other resistance mechanisms, such as porin mutations or efflux pumps.1 The eCIM showed metallo-β-lactamase was dominant in two tertiary care hospitals in Manado and Malang. The results of the research are by research conducted in Washington and dr. Soetomo Hospital, Surabaya.21,25
The CRAB carrying resistance genes of blaKPC, blaNDM, and blaOXA-23 were discovered in different countries.16,35-38 In our study, the result of carbapenemase resistance genes at dr. Saiful Anwar Hospital, Malang identified two specimens (4.7%) were positive for blaNDM carbapenemase resistance gene, and 39 specimens (90.7%) were positive for the blaOXA-23 gene. In Prof. dr. R. D. Kandou Hospital, Manado, identified one specimen (3.3%) was positive for the blaNDM gene, and 18 samples (60%) were positive for the blaOXA-23 gene. The results of this study were in accordance with the research in Jakarta, and it was obtained that the carbapenemase resistance genes blaNDM and blaOXA-23 (1.3%) and blaOXA-23 (91.8%),22 Japan obtained the carbapenemase resistance gene blaOXA-23 (85%),38 Egypt obtained blaNDM and blaOXA-23 (6%) and blaOXA-23 (86%) carbapenemase resistance genes,16 Iraq were discovered blaOXA-23 (75%),15 Los Angeles, California, USA found blaOXA-23 carbapenemase resistance gene (57.1%).14 This shows that the blaOXA-23 carbapenemase resistance gene is widespread globally, including in Southeast Asia.39
A study in two tertiary care hospitals in Malang and Manado found some samples positive result of carbapenemase-production, but no blaKPC, blaNDM, and blaOXA-23 genes were detected. Therefore, further research is needed on the other carbapenemase resistance genes and also investigating the other antibiotic resistance mechanisms, such as porin mutations and efflux pumps,7,37,38,40 biofilm formation,41 and alternative antimicrobial.42,43
Our study is limited by first, our study only two-center study, so it is not necessarily representative of our entire country, but can be used as a reference point. Second, we did not evaluate the other carbapenem resistance genes and resistance mechanism, that bacterial porin and efflux pump. Third, the colistin antibiotic was not tested.
CONCLUSION:
We detected CRAB positive result of carbapenemase-production and carbapenemase resistance genes of blaOXA-23 seem to be dominant. Further investigation is needed to analyze the clonality of the CRAB isolate for infection prevention control purposes.
CONFLICTS OF INTEREST:
The authors have no conflicts of interest regarding this investigation.
ACKNOWLEDGEMENTS:
The authors would like to thank the funding of this research and first author’s Doctoral study provided by Ministry of Education, Culture, Research and Technology Republic of Indonesia.
REFERENCES:
1. Potron A, et al. Emerging broad-spectrum resistance in Pseudomonas aeruginosa and Acinetobacter baumannii: Mechanisms and epidemiology. International Journal of Antimicrobial Agents. 2015; 45 (6): 568-85. doi: 10.1016/j.ijantimicag.2015.03.001.
2. Moubareck CA, Halat DH. Insights into Acinetobacter baumannii: A review of microbiological, virulence, and resistance traits in a threatening nosocomial pathogen. Antibiotics. 2020; 9 (3): 1-29. doi: 10.3390/antibiotics9030119.
3. Queenan AM, et al. Multidrug resistance among Acinetobacter spp. in the USA and activity profile of key agents: Results from CAPITAL Surveillance 2010. Diagnostic Microbiology and Infectious Disease. 2012; 73 (3): 267-70. doi: 10.1016/j.diagmicrobio.2012.04.002.
4. Tawfik DM, et al. The detection of antigenic determinants of Acinetobacter baumannii. Immunology Letters. 2017; 186: 59-67. doi: 10.1016/j.imlet.2017.04.004.
5. Tjoa E, et al. Acinetobacter baumannii: Role in blood stream infection in Neonatal Unit, Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia. International Journal of Microbiology. 2013; 2013: 1-6. doi: 10.1155/2013/180763.
6. CDC US. Antibiotic resistance threats in the United States, 2019,” Atlanta, Georgia. 2019. doi: 10.15620/cdc:82532.
7. Manchanda V, et al. Multidrug resistant Acinetobacter. Journal of Global Infectious Diseases. 2010; 2 (3): 291-304. doi: 10.4103/0974-777x.68538.
8. Poirel L, et al. Genetic basis of antibiotic resistance in pathogenic Acinetobacter species. IUBMB Life. 2011; 63 (12): 1061-67. doi: 10.1002/iub.532.
9. Ramalingam AJ. History of Antibiotics and Evolution of Resistance. Research J. Pharm. and Tech. 8 (12): Dec., 2015; Page 1719-24. doi: 10.5958/0974-360X.2015.00309.1.
10. Héritier C, et al. Cephalosporinase over-expression resulting from insertion of ISAba1 in Acinetobacter baumannii. Clinical Microbiology and Infection. 2006; 12 (2): 123-30. doi: 10.1111/j.1469-0691.2005.01320.x.
11. Sun K, et al. Evaluation of six phenotypic methods for the detection of carbapenemases in gram-negative bacteria with characterized resistance mechanisms. Annals of Laboratory Medicine. 2017; 37 (4): 305-12. doi: 10.3343/alm.2017.37.4.305.
12. Maragakis LL, Perl TM. Acinetobacter baumannii: epidemiology, antimicrobial resistance, and treatment options. Clin Infect Dis. 2008; 46 (8): 1254-63.
13. Evans, BA, et al. (2013). The rise of carbapenem-resistant Acinetobacter baumannii. Current Pharmaceutical Design. 2013; 19: 223-38. doi: 10.2174/1381612811306020223.
14. El-Shazly S, et al. Molecular epidemiology and characterization of multiple drug-resistant (MDR) clinical isolates of Acinetobacter baumannii. International Journal of Infectious Diseases. 2015; 41: 42-9. doi: 10.1016/j.ijid.2015.10.016.
15. Al-Hindawi RA, Jarallah EM. Detection of AmpC gene and Some OXA β-lactamase class among Carbapenem Resistant Acinetobacter baumannii (CRAB) isolates in Hilla, Iraq. Research J. Pharm. and Tech 2018; 11 (2):777-84. doi: 10.5958/0974-360X.2018.00147.6
16. El Bannah AMS, et al. Molecular Epidemiology of Carbapenem-Resistant Acinetobacter baumannii in a Tertiary Care Hospital in Egypt: Clonal Spread of bla OXA-23. Microbial Drug Resistance. 2017; 24 (3): 269-77. doi: 10.1089/mdr.2017.0057.
17. Doi Y, et al. Acinetobacter baumannii: Evolution of antimicrobial resistance-treatment options. Seminars in Respiratory and Critical Care Medicine. 2015; 36 (01): 85-98. doi: 10.1055/s-0034-1398388.
18. Xu Y, et al. Epidemiology of carbapenem resistant Enterobacteriaceae (CRE) during 2000-2012 in Asia. Journal of Thoracic Disease. 2015; 7 (3): 376-85. doi: 10.3978/j.issn.2072-1439.2014.12.33.
19. Peleg AY, et al. Acinetobacter baumannii: Emergence of a successful pathogen. Clinical Microbiology Reviews. 2008; 21 (3): 538-82. doi: 10.1128/CMR.00058-07.
20. Wang CH, et al. Outbreak of imipenem-resistant Acinetobacter baumannii in different wards at a regional hospital related to untrained bedside caregivers. American Journal of Infection Control. 2017; 45 (10): 1086-90. doi: 10.1016/j.ajic.2017.04.016.
21. Kuntaman K, et al. Occurrence and characterization of carbapenem-resistant Gram-negative bacilli: A collaborative study of antibiotic-resistant bacteria between Indonesia and Japan. International Journal of Urology. 2018; 25 (11): 966-72. doi: 10.1111/iju.13787.
22. Saharman YR, et al. Endemic carbapenem-nonsusceptible Acinetobacter baumannii-calcoaceticus complex in intensive care units of the national referral hospital in Jakarta, Indonesia. Antimicrobial Resistance and Infection Control. 2018; 7 (5): 1-12. doi: 10.1186/s13756-017-0296-7.
23. Aliramezani A, et al. Clonal relatedness and biofilm formation of OXA-23-producing carbapenem resistant Acinetobacter baumannii isolates from hospital environment. Microbial Pathogenesis. 2016; 99: 204-08. doi: 10.1016/j.micpath.2016.08.034.
24. “Clinical and Laboratory Standards Institute,” 2019.
25. McMullen AR, et al. Evaluation of genotypic and phenotypic methods to detect carbapenemase production in gram-negative bacilli. Clinical Chemistry. 2017; 63 (3): 723-30. doi: 10.1373/clinchem.2016.264804.
26. Simner PJ, et al. Multicenter evaluation of the modified carbapenem inactivation method and the carba NP for detection of carbapenemase-producing Pseudomonas aeruginosa and Acinetobacter baumannii,” Journal of Clinical Microbiology. 2018; 56 (1): 1-10. doi: 10.1128/JCM.01369-17.
27. Halain AA, et al. Nursing Workload in Relation to Nosocomial Infection in Public Hospital Intensive Care Unit, Malaysia. Research J. Pharm. and Tech 2018; 11(9): 3892-96. doi: 10.5958/0974-360X.2018.00713.8
28. Rani U, et al. Factors Associated with Neonatal Healthcare-Associated Infections (HAIs) in India: A Protocol for Systematic Review and Meta-analysis. Research J. Pharm. and Tech. 2020; 13(4): 1672-8. doi: 10.5958/0974-360X.2020.00303.0
29. Li YJ, et al. Pneumonia caused by extensive drug-resistant Acinetobacter baumannii among hospitalized patients: Genetic relationships, risk factors and mortality. BMC Infectious Diseases. 2017; 17 (1): 1-10. doi: 10.1186/s12879-017-2471-0.
30. Helmy OM, Kashef MT. Different phenotypic and molecular mechanisms associated with multidrug resistance in Gram-negative clinical isolates from Egypt. Infection and Drug Resistance. 2017; 10: 479-98. doi: 10.2147/IDR.S147192
31. Lin CY, et al. Risk factors of multidrug-resistant Acinetobacter baumannii recurrence after successful eradication in ventilated patients. Biomedical Journal. 2016; 39 (2): 130-8. doi: 10.1016/j.bj.2015.07.001.
32. Shrestha S, et al. Molecular epidemiology of multidrug-resistant Acinetobacter baumannii isolates in a university hospital in Nepal reveals the emergence of a novel epidemic clonal lineage. International Journal of Antimicrobial Agents. 2015; 46 (5): 526-31. doi: 10.1016/j.ijantimicag.2015.07.012.
33. Reshmi B, Gopinath P. Detection of blaNDM-1gene for the production of MBL in Clinical Strains of Klebsiella pneumoniae. Research J. Pharm. and Tech 2016; 9 (10):1618-20. doi: 10.5958/0974-360X.2016.00321.8
34. Varshan R, Prakasam G. Detection of blaVIM gene encoding Metallo Beta Lactamase resistance among clinical isolates of Pseudomonas aeruginosa. Research J. Pharm. and Tech 2016; 9 (9):1465-8. doi: 10.5958/0974-360X.2016.00284.5
35. Yang HY, et al. Outbreaks of imipenem resistant Acinetobacter Baumannii producing OXA-23 β-lactamase in a Tertiary Care Hospital in Korea. Yonsei Medical Journal. 2009; 50 (6): 764-70. doi: 10.3349/ymj.2009.50.6.764.
36. Sohrabi N, et al. Prevalence of oxa-type β-lactamases among Acinetobacter baumannii isolates from northwest of Iran. Microbial Drug Resistance. 2012; 18 (4): 385-9. doi: 10.1089/mdr.2011.0077.
37. Merino M, et al. Nosocomial outbreak of a multiresistant Acinetobacter baumannii expressing OXA-23 carbapenemase in Spain. Microbial Drug Resistance. 2014; 20 (4): 259-63. doi: 10.1089/mdr.2013.0127.
38. Kubo Y, et al. Spread of OXA-23-producing Acinetobacter baumannii ST2 and ST246 in a hospital in Japan. Journal of Medical Microbiology. 2015; 64 (7): 739-44. doi: 10.1099/jmm.0.000077.
39. Hsu LY, et al. Carbapenem-resistant Acinetobacter baumannii and Enterobacteriaceae in South and Southeast Asia. Clinical Microbiology Reviews. 2017; 30 (1): 1-22. doi: 10.1128/CMR.00042-16.
40. AL-Harmoosh RA, et al. Detection of Efflux Pumps Genes in Clinical Isolates of Acinetobacter baumannii . Research J. Pharm. and Tech 2017; 10 (12): 4231-6. doi: 10.5958/0974-360X.2017.00775.2
41. Kareem MH, Hasan AY. Inhibition of Biofilm formation of Imipenem-resistant Acinetobacter baumannii using Curcuma longa extracts, silver nanoparticles and Azithromycin. Research J. Pharm. and Tech 2019; 12 (9):4463-70. doi: 10.5958/0974-360X.2019.00769.8
42. Sharmalkumar M, et al. In-vitro study on Antimicrobial and Anticancer activities of marine sponge Clathria frondifera associated bacteria. Research J. Pharm. and Tech. 2020; 13 (8):3753-8. doi: 10.5958/0974-360X.2020.00664.2
43. Kumar U, et al. Benzimidazole: Structure Activity Relationship and Mechanism of Action as Antimicrobial Agent. Research J. Pharm. and Tech. 2017; 10 (7): 2400-14. doi: 10.5958/0974-360X.2017.00425.5
Received on 03.08.2021 Modified on 28.09.2021
Accepted on 03.11.2021 © RJPT All right reserved
Research J. Pharm. and Tech. 2022; 15(7):2917-2922.
DOI: 10.52711/0974-360X.2022.00486