Get Permission Singhsamanta, Dubey, Rath, and Das: Prevalence β-lactam resistant Pseudomonas aeruginosa strains isolated from chronic suppurative otitis media infections: A single center survey in Eastern India


Introduction

Among middle ear infections, chronic suppurative otitis media (CSOM) is one of the most prevalent, especially in youngsters. It occasionally results in acute otitis media but is often characterized by chronic middle ear drainage and tympanic membrane proportion.1, 2 In the present era of antibiotics, CSOM may be infrequent in developed countries; however, it is pervasive in third-world countries, where a need for rapid diagnosis and standard medical facilities are unavailable. Untreated CSOM infections may lead to petrositis, facial paralysis, labyrinthitis, lateral sinus thrombophylactic, meningitis and other complications such as hearing loss and intracranial absences. 3 The most frequently isolated bacterial organisms from CSOM patients are Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Proteus mirabilis, Klebsiella species, and fungi like Aspergillus and Candida. Causative organisms may often vary depending on the climatic and geographical conditions of the patients. 4, 5 Primarily, CSOM is treated with antibiotic drugs such as neomycin, gentamicin, tobramycin, and aminoglycosides. However, with the advent of multidrug-resistant (MDR) bacteria, particularly P. aeruginosa, E. coli, and S. aureus, treatment of CSOM infection has become difficult. 6, 7, 8

P. aeruginosa is one of the most common Gram-negative bacteria isolated from CSOM patients. This bacterium generally damages the mucosal epithelium of the middle ear, resulting in acute otitis media and sometimes a form of biofilm in the middle ear. 6 The biofilm formation resists the topical antibiotic treatment, leading to complications in the treatment procedure. 7 Moreover, P. aeruginosa releases several virulence factors, such as toxins and enzymes like proteases and elastases, which facilitate tissue damage and the rapid spread of infection. Additional virulence factors that cause adherence and invasion of their host include mucoid exopolysaccharide, pili, exotoxin A, lipopolysaccharide, pigments, lipase, haemolysin, histamine, exoenzyme S, leucocidin, and rhamnolipids. These factors also weaken the host's immune responses and an antibiotic barrier formed by it. 9, 10 Further, these strains harbour multiple mechanisms like antibiotic efflux, production of antibiotic resistance enzymes, and mutations in antibiotic target sides, making the antibiotic treatment ineffective. 11, 12

For millions of years, P. aeruginosa has lived in the soil alongside antibiotic-producing bacilli, actinomycetes, and moulds, allowing it to build resistance to various naturally occurring antibiotics. The main mechanisms behind beta-lactam resistance in P. aeruginosa strains include targeting beta-lactam antibiotics, such as cephalosporins, penicillin, and other similar drugs, by changing the outer membrane proteins and altering the penicillin-binding proteins. 11, 12 Certain strains possess inherent resistance mechanisms, known as intrinsic mechanisms, or they can be acquired through mutations or horizontal gene transfer. Treatment of bacterial infections with beta-lactam antibiotics is made more difficult by disseminating resistance genes, primarily via plasmids and transposons. The commonly found β-lactamases-producing strains of P. aeruginosa are Extended-spectrum- β-lactamases (ESBLs) producing strains, Metallo-β-lactamases (MBLs) and AmpC-producing strains. 13, 14

β-lactamase-producing P. aeruginosa strains often lead to treatment failure as the β-lactamase present in the organisms breaks down the β-lactam antibiotics. These resistant bacteria require the use of more toxic antibiotics for treatment. They increase the health care cost and duration of hospitalization and increase the chances of higher morbidity and mortality rates. 15, 16 Further complications, such as nosocomial infections like urinary tract infections and ventilator-associated pneumonia, become familiar and lead to outbreaks in nursing homes and hospitals. Resistant strains of P. aeruginosa can survive in several environmental conditions and serve as a reserve of antibiotic-resistant genes that can be transferred to other bacteria. Particularly in CSOM patients, β-lactamase, producing P. aeruginosa, limits the treatment choice, leading to resistance ear discharge and chronic middle ear inflammation. Further conductive hearing loss and sensorineural hearing loss are also seen in some patients. The infection may spread to the mastoid bone, leading to mastoiditis and other threatening infections, such as meningitis, brain abscess, and lateral sinus thrombosis. 17, 18 Therefore, this study aims to determine the prevalence of β-Lactam resistant P. aeruginosa strains isolated from patients with CSOM infections attending a tertiary care hospital in eastern India.

Materials and Methods

Sample collection

Ear swabs from 100 CSOM patients, of which 76 were males (mean age 46), and 24 were females (mean age 41), who reported to the outpatient Department of Otorhinolaryngology, IMS, and Sum Hospital (a multispeciality hospital in Eastern India) were collected from April to June 2023. The collected swabs were aseptically transferred to the medical research laboratory of the same hospital for the isolation and identification of the causative organism. This study was conducted after the approval of the institutional ethical committee of IMS, and Sum Hospital vide letter no: IEC/IMS.SH/SOA/2022/403 dated 22nd August 2022.

Bacterial identification and antibiotic sensitivity test

The bacterial identification was made by culturing the swab samples on the different culture media: Nutrient, McConkey, and Blood agar. The major isolated bacterial colonies were subjected to gram staining and biochemical tests as described elsewhere. 5, 6 The Kirby Bauer method was employed to determine the antibiotic sensitivity pattern using the commonly prescribed antibiotics for CSOM patients per the previously described protocol. 5, 6

In vitro assays for determining virulence factors of isolated P. aeruginosa strains

Swarming motility test

The isolated P. aeruginosa strains were inoculated into 1.5% Luria-Bertani (LB) agar plates with the help of an inoculation needle and were incubated at 37°C for 24 hours. The swarming zone formation around the inoculation streak confirmed the motility of the isolated strains. 19

Biofilm formation assay

The isolated P. aeruginosa strains were subjected to a biofilm development experiment utilising the microtiter plate technique. The strains of P. aeruginosa were diluted by LB broth to an optical density (OD) of 600nm (nearly 108 colony forming units/ml).200µl of the diluted P. aeruginosa culture was inoculated to each well of 96 wells of microtiter plate with proper levelling, and it was incubated for 48 hours at 37°C. After incubation, the planktonic cells were removed using a micropipette from each well. The cells were gently washed with sterilized buffer saline. Further, 1% crystal violet was used for 15 minutes to stain the adherent biofilm. The excess strains were washed gently in the water. The crystal violet strains were solubilized by adding 200µl of ethanol, and the absorbance was recorded for each well at 570nm using a microplate Elisa reader. 20

Haemolysis assay

The isolated P. aeruginosa strains were inoculated in 5% sheep blood agar plates and incubated at 12 hours at 37°C.β-haemolysis was confirmed by a clear zone around the colonies.21

Protease production assay

In a shaker incubator, the isolated P. aeruginosa strains were incubated from LB broth at 37°C. 10µl of overnight P. aeruginosa cultures was spot inoculated onto skim milk agar plate and incubated at 37°C for 24 hours. Post incubation, the clear zone around the bacteria colonies indicates the protease activity. 22

Pyocyanin production assay

The isolated P. aeruginosa strains were inoculated in LB broth at 37°C for 24 hours in a shaker incubator. Pyocyanin was extracted by adding an equal volume of chloroform to the culture, followed by vigorous vortexing and centrifuging to separate phases. The pyocyanin was collected with the chloroform layer mixed with the 2-molar hydrochloric acid. The absorbance of redissolved pyocyanin was taken at 520nm using a visible spectrophotometer. A reference absorbance of 700nm was taken to correct any background absorbance. The pyocyanin concentration was calculated using the formula: The pyocyanin concentration (μg/mL) = OD 520 × 17.072.23

Phenotypic determination of β-lactamase

The phenotypic detection of ESBLs, MBLs, AmpC and carbapenemase among the P. aeruginosa isolates was done by double disk synergic test as per CLSI guidelines 2023, meropenem-EDTA combined disc diffusion test, ceftazidime-boronic acid combined disc diffusion test and Modified Hodge test respectively. 24, 25, 26, 27, 28

Genotypic determination of β-lactamase

The genotypic detection of different classes of β-lactamase (amber class A- blaSHV & blaTEM, amber class B- blaVIM, blaIMP & blaNDM, amber class C- AmpC and amber class D- blaOXA & blaKPC, genes were sequentially determined by PCR using specific primers. After incubation, the LB plate was lysed at 94°C, taken in 500µl of sterile water, and transferred to the ice for 10 minutes. After centrifuging the solution at 13,000 rpm for 1 minute at 4˚C, 1.5 µl of the suspension was immediately employed as template DNA. 25µl master mix contains 5µl (5X) Promega PCR buffer, 2µl (25mM) MgCl2, 2µl (2.5mM/dNTP) dNTP, 1.5µl (10µM) Forward primer, 1.5µl (10µM) reverse primer, 0.5 µl Taq polymerase, 1.5 µl template and volume maintained by Milli-Q water. The amplified PCR product was run in 1.2% agarose gel at 60V for 45 minutes and visualized in a Gel-Doc apparatus. 29, 30, 31

Results

In this study P. aeruginosa strains were identified based on colony characteristics of Nutrient agar, McConkey agar, and Blood agar, as described in (Table 1), (Figure 1 a,b&c). It is a gram-negative bacillus, giving positive results for catalase, citrate, and nitrate reduction tests, whereas negative results for indole, methyl-red, Voges Proskauer and H2S tests (Table 1).

Table 1

Microbiological and biochemical identification of isolated P. aeruginosa strains from CSOM swabs.

Total Samples

Samples with P. aeruginosa strains

Colony characters

Biochemical characters

100

67

Nutrient agar

large opaque and flat colonies with irregular margins and earthy odour.

Gram-negative; positive for catalase, citrate, and nitrate reduction. Negative for Indole, Methyl red, Voges Proskauer and H2S test.

McConkey agar

Non-lactose fermenting flat, circular, colourless colonies

Blood agar

β haemolytic mucoid colonies with a metallic sheen.

Table 2

In vitro virulence tests of isolated P. aeruginosa strains.

Virulence tests

Number of strains responding to virulence test

Swarming Motility test

67 (100%)

Pyocyanin production assay

67(100%)

Biofilm formation assay

42(62.68%)

Protease

54 (80.59%)

Haemolysis assay

67(100%)

In the in vitro virulence tests, all the isolated 67 strains had positive results for the swarming motility pyocyanin production and haemolysis assay. However, only 42 strains had biofilm formation and protease production capacity (Table 2, Figure 2a, b & c).

The antibiotic sensitivity results found that all the 67 strains isolated were multidrug resistant, of which nearly 97.01% were resistant to gentamicin. Amoxicillin/ clavulanic was the antibiotic with the least resistance (47.76%) recorded. Resistance to β- lactamase antibiotics such as ceftriaxone, cefoperazone, cefuroxime imipenem and meropenem ranged between 72% to 88%, which signifies that these antibiotics are almost insignificant in the current treatment regimen of CSOM (Table 3).

Table 3

Antibiotic sensitivity pattern of the isolated P. aeruginosa strains.

Antibiotics

Number of isolated P. aeruginosa strains resistant to prescribed antibiotics (n = 67)

Resistance percentage (%) to P. aeruginosa strains (n = 67)

Ampicillin

46

67.71

Amoxicillin/Clavulanic Acid

32

47.76

Amikacin

54

80.59

Ceftriaxone

59

88.08

Ciprofloxacin

54

80.59

Cotrimoxazole

47

70.14

Cefoperazone/Sulbactam

53

71.10

Cefuroxime

51

76.11

Gentamicin

65

97.01

Imipenem

52

77.61

Meropenem

47

70.14

Piperacillin/Tazobactam

43

64.17

Tigecycline

46

67.71

Table 4

Phenotypic tests for determination β-lactamase producing P. aeruginosa strains.

Phenotypic tests for β-lactamase producers

Number of strains [n=67 (100 %)]

ESBLs

57 (85.07%)

MBLs

59 (88.05%)

AmpC

52 (77.61%)

Carbapenemase

54 (80.59%)

In the phenotypic test done for the determination of β- lactamase-producing P. aeruginosa strains (Figure 3), out of 67 strains, 57 (85.07%) were ESBL, 59 (88.05%) were MBL, 52 (77.61%) were AmpC producers, and 54 (80.59%) were carbapenemase enzyme producers (Table 4). From the above findings, it can be interpreted that isolated strains had multiple mechanisms for breaking down β-lactam antibiotics.

Table 5

Genotypic determination of P. aeruginosa strains harbouring β-lactamase genes.

β-lactamase genes

Number of isolated strains harbouring β-lactamase genes [n=67 (100%)]

amber class A blaSHV & blaTEM

54 (80.59%)

amber class B blaVIM, blaIMP & blaNDM

54 (80.59%)

amber class C AmpC

52 (77.61%)

amber class D blaOXA & blaKPC,

51 (76.11%)

In the genotypic determination of P. aeruginosa strains harbouring β-lactamase genes, it was recorded that 54 (80.59%) strains harboured amber class A β-lactamase genes, 54 (80.59%) strains harboured amber class B gene, 52 (77.61%) strains contained amber class C gene, and 51(76.11%) strains contained amber class D β- lactamase gene. (Table 5). Hence, it can be inferred that the isolated strains from the CSOM patients harboured more than two types of β-lactamase-producing genes, which makes them MDR bacteria.

Figure 1

Growth of Pseudomonas aeruginosa on: a: Nutrient agar; b: McConkey agar; c: Blood agar.

https://s3-us-west-2.amazonaws.com/typeset-prod-media-server/a107eeaf-ac41-498d-bc1a-3f36dd6d0701image1.jpeg
Figure 2

In vitro evaluation of inherent virulence factors the isolated Pseudomonas aeruginosa produces: a: Swarming motility test; b: Haemolysis assay; c: Protease production assay.

https://s3-us-west-2.amazonaws.com/typeset-prod-media-server/a107eeaf-ac41-498d-bc1a-3f36dd6d0701image2.jpeg
Figure 3

Double disk diffusion test for phenotypic detection of β lactamase enzyme production.

https://s3-us-west-2.amazonaws.com/typeset-prod-media-server/a107eeaf-ac41-498d-bc1a-3f36dd6d0701image3.jpeg

Discussion

The current study demonstrated the problem of multiple antibiotic resistance in Pseudomonas strains. The results obtained from the antibiotic sensitivity test following the conformation by phenotypic and genotypic tests were done for conforming β-lactamase producing P. aeruginosa strains. For instance, 52 strains conformed to harbouring amber class C AmpC genes in phenotypic and genotypic tests. Likewise, there was a marginal difference in the genotypic test. Some strains of P. aeruginosa did not contain the β-lactamase genes, which initially identified the phenotypic test. Hence, based on the current findings, we can confirm that the CSOM patients were infected with P. aeruginosa strains, ESBL, MBL, AmpC producers, and carbapenem producers or, in other words, PAN drug resistance bacteria. A study from Odisha, India, isolated 371 MDR P. aeruginosa strains from CSOM patients who were resistant to antibiotics, particularly the β-lactam group. 32 Similarly, from South India, from 106 CSOM patients, 49 MDR P. aeruginosa strains are isolates highly resistant to β-lactam and carbapenem group of antibiotics. 33 ESBL P. aeruginosa strains were isolated from CSOM patients from a study in North India, which accounted for 36% of the total infections. 34 Similarly, in another Indian study, it was reported that ESBL-producing P. aeruginosa strains accounted for nearly 41.2% of the total infection, which was spread across all patients in each group. 35

Earlier research studies have demonstrated the relationship between the β-lactamase-producing genes and virulence factors. 36, 37 It is established that harbouring β-lactamase producing gene increases the degree of virulence and the organism’s adaptability to different environmental conditions.38 For example, the blaAmpC gene increases the proteolytic activity of the bacteria as the blaVIM and blaIMP genes are associated with the biofilm formation capacity of Pseudomonas strains. 39 Acquisition of the β-lactamase resistance gene also triggers the efflux plumps of P. aeruginosa strains, making the organisms resistant to other antibiotics like quinones and aminoglycosides. It initiates a pathway for cross-regulation of antibiotic resistance that develops new resistance genes in the genetic pool. This antibiotic resistance of genes can quickly transfer to other species of bacteria, particularly in clinical settings. 40 Therefore, doing more studies to determine the relationship between β-lactamase genes and other virulence factors of P. aeruginosa strains might be interesting.

Several studies have shown that P. aeruginosa was a leading causative organism in CSOM patients, which were β-lactamase producers. A study from Nigeria detected the FOX- AmpC β-lactamase gene in the P. aeruginosa strains isolated from CSOM patients. 41 Likewise, a study from Ethiopia detected ESBL-producing Proteus mirabilis, P. aeruginosa, and Klebsiella pneumoniae strains in more than 238 patients with ear infections. 42 A study from Bangladesh reported a predominance of ESBL strains of P. aeruginosa over three years in a study conducted in two tertiary care hospitals. This study also reported that P. aeruginosa strains are resistant to aminoglycoside. 43 Similarly, ESBL P. aeruginosa strains have also been reported in poultry environments in Bangladesh. 44 From a Sri Lankan study, a high % of ESBL P. aeruginosa strains were isolated from ICU patients, majorly hospital-born infections. 45 Similarly, P. aeruginosa strains harbouring all kinds of ESBL genes were reported from diabetic food ulcer patients attending a medical university in Pakistan. 46 A recent study from Kathmandu, Nepal, also reported the prevalence of ESBL and MBL P. aeruginosa strains from two tertiary care hospitals conducted over a period of 2 years. 47 The above study shows the dominance of P. aeruginosa ESBL strains in CSOM patients and all other infections in hospitals and community settings, as seen in our study.

Conclusion

The present study gives a complete idea of the prevalence of β-lactamase producing P. aeruginosa strains in CSOM patients. As established, the resistance gene also enhances the virulence and pathogenicity of P. aeruginosa strains. Therefore, it decreases treatment options, creating a clinical concentration among the clinicians. Therefore, a modified antibiotic usage policy should be employed in hospitals to reduce the global burden of MDR P. aeruginosa strains and other MDR bacteria. As time progresses, this global burden of MDR bacteria will lead to a post-antibiotic era in which any majors may not control them. Hence, the immediate scientific major should be taken to reduce the exitance of the MDR bacteria.

Source of Funding

None.

Conflict of Interest

None.

References

1 

R Mittal CV Lisi R Gerring Current concepts in the pathogenesis and treatment of chronic suppurative otitis mediaJ Med Microbiol20156410110316

2 

M Khairkar P Deshmukh H Maity V Deotale Chronic Suppurative Otitis Media: A Comprehensive review of epidemiology, pathogenesis, microbiology, and complicationsCureus20231584372910.7759/cureus.43729

3 

N Sharma AA Jaiswal PK Banerjee AK Garg Complications of Chronic Suppurative Otitis Media and Their Management: A Single Institution 12 Years ExperienceIndian J Otolaryngol Head Neck Surg201567435360

4 

WNAW Draman MK Md Daud H Mohamad SA Hassan NA Rahman Abd Rahman N. Evaluation of the current bacteriological profile and antibiotic sensitivity pattern in chronic suppurative otitis mediaLaryngoscope Investig Otolaryngol20216613006

5 

MC Sahu D Dubey S Rath NK Debta RN Padhy Multidrug resistance of Pseudomonas aeruginosa as known from surveillance of nosocomial and community infections in an Indian teaching hospitalJ Public Health2012204132310.1007/s10389-011-0479-2

6 

MC Sahu SK Swain SK Kar Genetically Diversity of Pseudomonas aeruginosa isolated from chronic suppurative otitis media with respect to their antibiotic sensitivity patternIndian J Otolaryngol Head Neck Surg201971S213008

7 

S Rath RN Padhy Surveillance of multidrug resistance of 10 enteropathogens in a teaching hospital and in vitro efficacy of 25 ethnomedicinal plants used by an Indian aborigineAsian Pacif J Trop Dis20122133646

8 

D Dubey S Rath MC Sahu L Pattnaik NK Debata RN Padhy Surveillance of infection status of drug-resistant Staphylococcus aureus in an Indian teaching hospitalAsian Pac J Trop Dis20133213342

9 

S Qin W Xiao C Zhou Q Pu X Deng L Lan Pseudomonas aeruginosa: pathogenesis, virulence factors, antibiotic resistance, interaction with host, technology advances and emerging therapeuticsSignal Transduct Target Ther20227119910.1038/s41392-022-01056-1

10 

R Mittal CV Lisi H Kumari M Grati P Blackwelder D Yan Otopathogenic Pseudomonas aeruginosa Enters and Survives Inside MacrophagesFront Microbiol20167182810.3389/fmicb.2016.01828

11 

MAS Ahmed FA Khan AA Sultan B Söderquist EB Ibrahim J Jass β-lactamase-mediated resistance in MDR-Pseudomonas aeruginosa from QatarAntimicrob Resist Infect Control20209117010.1186/s13756-020-00838-y

12 

KA Glen IL Lamont β-lactam Resistance in Pseudomonas aeruginosa: Current StatusFuture Prospects. Pathogens20211012163810.3390/pathogens10121638

13 

A Elfadadny RF Ragab M Alharbi F Badshah E Ibáñez-Arancibia A Farag Antimicrobial resistance of Pseudomonas aeruginosa: navigating clinical impacts, current resistance trends, and innovations in breaking therapiesFront Microbiol202415137446610.3389/fmicb.2024.1374466

14 

S Kamal K Varshney DJ Uayan BG Tenorio P Pillay ST Sava Risk Factors and clinical characteristics of pandrug resistant Pseudomonas aeruginosaCureus20241645811410.7759/cureus.58114

15 

JJ Song BD Lee KH Lee JD Lee YJ Park MK Park Changes in antibiotic resistance in recurrent Pseudomonas aeruginosa infections of chronic suppurative otitis mediaEar Nose Throat J20169510-1144651

16 

N Sathe P Beech L Croft C Suphioglu A Kapat E Athan Pseudomonas aeruginosa: Infections and novel approaches to treatment "Knowing the enemy" the threat of Pseudomonas aeruginosa and exploring novel approaches to treatmentInfect Med (Beijing)20232317894

17 

N Sharma AA Jaiswal PK Banerjee AK Garg Complications of Chronic Suppurative Otitis Media and Their Management: A Single Institution 12 Years ExperienceIndian J Otolaryngol Head Neck Surg201567435360

18 

J Xu Q Du Y Shu J Ji C Dai Bacteriological Profile of Chronic Suppurative Otitis Media and Antibiotic Susceptibility in a Tertiary Care Hospital inEar Nose Throat J202110093916

19 

DG Ha SL Kuchma GA O’Toole Plate-based assay for swimming motility in Pseudomonas aeruginosaMethods Mol Biol20141149596510.1007/978-1-4939-0473-0_7

20 

GA O'Toole Microtiter dish biofilm formation assayJ Vis Exp201147243710.3791/2437

21 

M Georgescu I Gheorghe C Curutiu V Lazar C Bleotu MC Chifiriuc Virulence and resistance features of Pseudomonas aeruginosa strains isolated from chronic leg ulcersBMC Infect Dis20161619210.1186/s12879-016-1396-3

22 

RZ Suleiman BS Noomi IO Saeed Detection of virulence factors of Pseudomonas aeruginosa isolated from clinical samplesEur Chem Bull2023129148290

23 

M Muller ND Merrett Pyocyanin production by Pseudomonas aeruginosa confers resistance to ionic silverAntimicrob Agents Chemother201458954929

24 

Pennsylvania: Clinical and Laboratory Standards Institute; 2023. Performance Standards for Antimicrobial Susceptibility TestingM100: Performance Standards for Antimicrobial Susceptibility Testing32ndCLSI Supplement M100\RWayne2023https://clsi.org/about/press-releases/clsi-publishes-m100-performance-standards-for-antimicrobial-susceptibility-testing-32nd-edition/

25 

S Rath D Dubey MC Sahu RN Padhy Surveillance of ESBL-producing multidrug-resistant Escherichia coli in a teaching hospital in IndiaAsian Pac J Trop Dis2014421409

26 

M Rouf A Nazir O Karnain S Akhter Comparison of Various Phenotypic Methods in Detection of Carbapenemases and Metallo-Beta-Lactamases (MBL) in Carbapenem Resistant Clinlical Isolates of Acinetobacter Species at A Tertiary Care CentreJ Res Appl Basic Med Sci2022831107

27 

R Elsherif D Ismail S Elawady S Jastaniah S Al-Masaudi S Harakeh Boronic acid disk diffusion for the phenotypic detection of polymerase chain reaction-confirmed, carbapenem-resistant, gram-negative bacilli isolatesBMC Microbiol201616113510.1186/s12866-016-0754-z

28 

A Amjad Mirza Ia S Abbasi U Farwa N Malik F Zia Modified Hodge test: A simple and effective test for detection of carbapenemase productionIran J Microbiol20113418993

29 

SM Farhan RA Ibrahim KM Mahran HF Hetta RM Abd El-Baky Antimicrobial resistance pattern and molecular genetic distribution of metallo-β-lactamases producing Pseudomonas aeruginosa isolated from hospitals in Minia, EgyptEgypt. Infect Drug Resist20191221253310.2147/IDR.S198373

30 

HA Abbas AM El-Ganiny HA Kamel Phenotypic and genotypic detection of antibiotic resistance of Pseudomonas aeruginosa isolated from urinary tract infectionsAfr Health Sci20181811121

31 

M Karampoor F Akhlaghi MR Mobayen F Afrasiabi R Khodayary M Moradzadeh Phenotypic and genotypic characterization of Metallo-β-lactamase producing Pseudomonas aeruginosa isolated from burn patientsNew Microbes New Infect202249-5010105910.1016/j.nmni.2022.1010

32 

S Rath SR Das RN Padhy Surveillance of bacteria Pseudomonas aeruginosa and MRSA associated with chronic suppurative otitis mediaBraz J Otorhinolaryngol20178322016

33 

C Shilpa S Sandeep U Thanzeemunisa B G Prakash S Radhika S Virender Current Microbiological Trends of Chronic Suppurative Otitis Media in a Tertiary Care Centre, Mysuru, IndiaIndian J Otolaryngol Head Neck Surg2019712144952

34 

R Sujatha BK Prasad N Afaq Arunagiri D Sameerdind Molecular characterization of metallo-beta lactamase geneblaimp-1 in imipenem resistant Pseudomonas aeruginosa isolates from patients of chronic suppurative otitis media at a tertiary care hospitalIP Int J Med Microbiol Trop Dis20228432430

35 

R Agrawal PK Khatri RS Parihar H Shah ESBL Mediated Resistance In Pseudomonas aeruginosa In CSOM Patients: An Emerging Threat To Clinical Therapeutics: ESBL Mediated Resistance in Pseudomonas aeruginosa in CSOM patientsNatl J Integr Res Med201881812

36 

S Dehbashi H Tahmasebi MR Arabestani Association between Beta-lactam Antibiotic Resistance and Virulence Factors in AmpC Producing Clinical Strains of P. aeruginosaOsong Public Health Res Perspect20189632533

37 

EA Edward MR El Shehawy A Abouelfetouh E Aboulmagd Prevalence of different virulence factors and their association with antimicrobial resistance among Pseudomonas aeruginosa clinical isolates from EgyptBMC Microbiol202323116110.1186/s12866-023-02897-8

38 

H Sharifi G Pouladfar M R Shakibaie B Pourabbas J Mardaneh S Mansouri Prevalence of β-lactamase genes, class 1 integrons, major virulence factors and clonal relationships of multidrug-resistant Pseudomonas aeruginosa isolated from hospitalized patients in southeast of IranIran J Basic Med Sci201922780612

39 

HK Musafer FN Jaafar MA Al-Bayati Association of Biofilm Inducer with bla VIM, bla IMP, and bla NDM in Pseudomonas aeruginosa IsolatesArch Razi Inst202277517238

40 

H Kumari D Balasubramanian D Zincke K Mathee Role of Pseudomonas aeruginosa AmpR on β-lactam and non-β-lactam transient cross-resistance upon pre-exposure to subinhibitory concentrations of antibioticsJ Med Microbiol20146345445

41 

IF Amadi OC Nchedo AT Obaji M Agbonifo E Eze IC Stacy Detection of FOX-AmpC-β-lactamase gene and antibiogram of AmpC-beta-lactamase-producing pathogens isolated from chronic suppurative otitis media patients in NigeriaIran J Microbiol202315677987

42 

K Endaylalu B Abera W Mulu Extended spectrum beta-lactamase producing bacteria among outpatients with ear infection at Felege Hiwot Referral Hospital, North West EthiopiaPLoS One202015923889110.1371/journal.pone.0238891

43 

S Begum MA Salam KF Alam N Begum P Hassan JA Haq Detection of extended-spectrum β-lactamase in Pseudomonas spp. isolated from two tertiary care hospitals in BangladeshBMC Res Notes20136710.1186/1756-0500-6-7

44 

R Islam FB Ferdous MN Hoque NA Asif ML Rana MP Siddique Characterization of β-lactamase and virulence genes in Pseudomonas aeruginosa isolated from clinical, environmental and poultry sources in BangladeshPLoS One202419429654210.1371/journal.pone.0296542

45 

K Tissera V Liyanapathirana N Dissanayake V Pinto A Ekanayake M Tennakoon Spread of resistant gram negatives in a Sri Lankan intensive care unitBMC Infect Dis201717149010.1186/s12879-017-2590-7

46 

FU Hassan MS Qudus SA Sehgal J Ahmed M Khan KU Haq Prevalence of Extended-Spectrum β-Lactamases in Multidrug-Resistant Pseudomonas aeruginosa from diabetic foot patientsEndocr Metab Immune Disord Drug Targets20191944438

47 

PM Shrestha HP Kattel S Sharma P Bista BK Basnet P Ghimire Metallo-β-lactamase-producing Pseudomonas aeruginosa isolates from two tertiary care centres in a district of Nepal: A descriptive cross-sectional StudyJ Nepal Med Assoc2024622712026



jats-html.xsl


This is an Open Access (OA) journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

  • Article highlights
  • Article tables
  • Article images

Article History

Received : 27-07-2024

Accepted : 22-08-2024


View Article

PDF File   Full Text Article


Copyright permission

Get article permission for commercial use

Downlaod

PDF File   XML File   ePub File


Digital Object Identifier (DOI)

Article DOI

https://doi.org/10.18231/j.ijmmtd.2024.045


Article Metrics






Article Access statistics

Viewed: 178

PDF Downloaded: 45



Medical Abbreviation List