Osong Public Health and Research Perspectives

Review Article

Strategies to combat Gram-negative bacterial resistance to conventional antibacterial drugs: a review: Priyanka Bhowmik, Barkha Modi, Parijat Roy, Antarika Chowdhury; Osong Public Health Res Perspect. 2023;14(5):333-346. Published online October 18, 2023; DOI: https://doi.org/10.24171/j.phrp.2022.0323

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The emergence of antimicrobial resistance raises the fear of untreatable diseases. Antimicrobial resistance is a multifaceted and dynamic phenomenon that is the cumulative result of different factors. While Gram-positive pathogens, such as methicillin-resistant Staphylococcus aureus and Clostridium difficile, were previously the most concerning issues in the field of public health, Gram-negative pathogens are now of prime importance. The World Health Organization’s priority list of pathogens mostly includes multidrug-resistant Gram-negative organisms particularly carbapenem-resistant Enterobacterales, carbapenem-resistant Pseudomonas aeruginosa, and extensively drug-resistant Acinetobacter baumannii. The spread of Gram-negative bacterial resistance is a global issue, involving a variety of mechanisms. Several strategies have been proposed to control resistant Gram-negative bacteria, such as the development of antimicrobial auxiliary agents and research into chemical compounds with new modes of action. Another emerging trend is the development of naturally derived antibacterial compounds that aim for targets novel areas, including engineered bacteriophages, probiotics, metal-based antibacterial agents, odilorhabdins, quorum sensing inhibitors, and microbiome-modifying agents. This review focuses on the current status of alternative treatment regimens against multidrug-resistant Gram-negative bacteria, aiming to provide a snapshot of the situation and some information on the broader context.

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Original Articles

Characterization of Antimicrobial Susceptibility, Extended-Spectrum β-Lactamase Genes and Phylogenetic Groups of Enteropathogenic Escherichia coli Isolated from Patients with Diarrhea: Erfaneh Jafari, Saeid Mostaan, Saeid Bouzari; Osong Public Health Res Perspect. 2020;11(5):327-333. Published online October 22, 2020; DOI: https://doi.org/10.24171/j.phrp.2020.11.5.09

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Abstract PDF

Objectives

Infectious diarrhea is one of the most common causes of pediatric death worldwide and enteropathogenic Escherichia coli (EPEC) is one of the main causes. There are 2 subgroups of EPEC, typical and atypical, based on the presence or absence of bundle forming pili (bfp), of which atypical EPEC is considered less virulent, but not less pathogenic. Antimicrobial resistance towards atypical EPEC among children is growing and is considered a major problem. In this study the pattern of antibiotic resistance in clinical isolates was determined.

Methods

Using 130 isolates, antibiotic resistance patterns and phenotypes were assessed, and genotypic profiles of extended spectrum β-lactamase (ESBL) production using disc diffusion and PCR was carried out. Phylogenetic groups were analyzed using quadruplex PCR.

Results

There were 65 E. coli isolates identified as atypical EPEC by PCR, among which the highest antibiotic resistance was towards ampicillin, followed by trimethoprim-sulfamethoxazole, and tetracycline. Multidrug resistance was detected in 44.6% of atypical EPEC isolates. Around 33% of isolates were determined to be extended spectrum β-lactamase producers, and in 90% of isolates, genes responsible for ESBL production could be detected. Moreover, the majority of atypical EPEC strains belonged to Group E, followed by Groups B1, B2 and C.

Conclusion

High rates of multidrug resistance and ESBL production among atypical EPEC isolates warrant periodical surveillance studies to select effective antibiotic treatment for patients. It is considered a critical step to manage antibiotic resistance by avoiding unnecessary prescriptions for antibiotics.

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Ntando W. Alfinete, John Y. Bolukaoto, Lee Heine, Natasha Potgieter, Tobias G. Barnard
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Mona Shaaban, Soha Lotfy Elshaer, Ola A. Abd El-Rahman
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Immunological Profile and Bacterial Drug Resistance in Pregnant Women: A Cross Sectional Study: Ornella JT Ngalani, Wiliane JT Marbou, Armelle Tsafack Mbaveng, Victor Kuete; Osong Public Health Res Perspect. 2020;11(5):319-326. Published online October 22, 2020; DOI: https://doi.org/10.24171/j.phrp.2020.11.5.08

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Abstract PDF Supplementary Material

Objectives

This study aimed to investigate the immunological and bacterial profiles in pregnant women of Bafang-Cameroon.

Methods

Stool and midstream urine were cultured using specific culture media. The disk diffusion method was used for the antimicrobial susceptibility test. T-cell lymphocyte counts (CD3, CD4 and CD8), white blood cell counts, sensitive C-reactive protein, and interleukin-6, were measured by flow cytometry, optical detection, and the enzyme-linked immunosorbent assay solid phase direct sandwich method.

Results

Out of 700 participants, 71.43% were pregnant, and 28.57% were non-pregnant women. The mean age was 29.40 ± 8.27 and 27.41 ± 6.55 years in non-pregnant and pregnant women, respectively. CD4 T-cells were not significantly lower in pregnant women compared with non-pregnant women. There were 43.65% and 56.35% bacteria isolates obtained from urine and stool samples, respectively. Bacteria were mostly isolated in patients with a CD4 T-cell count between 461 and 806 cells/μL. Isolates of Klebsiella pneumoniae and Enterobacter aerogenes showed 100% resistance in non-pregnant women, however all isolated bacteria were shown to be multidrug resistant in pregnant women. Salmonella sp. (24.3%) and Escherichia coli (21.51%) showed an increase in multidrug resistant phenotypes in pregnant women.

Conclusion

This study demonstrated that routine bacteriological analysis during pregnancy is necessary for their follow-up care.

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Michael F. Kengne, Ornella D. Tsobeng, Ballue S. T. Dadjo, Victor Kuete, Armelle T. Mbaveng, Tingtao Chen
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Haematological Profile and Antibiotic Resistance of Bacteria Responsible for Enteric Infections Isolated From Patients Suffering From Malaria and Enteric Infections on Consultation at the Dschang Regional Hospital
Roland Y. Ngai, Wiliane J. T. Marbou, Armelle T. Mbaveng, Victor Kuete, Mahmoud Elhaig
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Association between Beta-lactam Antibiotic Resistance and Virulence Factors in AmpC Producing Clinical Strains of P. aeruginosa: Sanaz Dehbashi, Hamed Tahmasebi, Mohammad Reza Arabestani; Osong Public Health Res Perspect. 2018;9(6):325-333. Published online December 31, 2018; DOI: https://doi.org/10.24171/j.phrp.2018.9.6.06

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Abstract PDF

Objectives

The purpose of this study was to determine the presence of IMP and OXA genes in clinical strains of Pseudomonas aeruginosa (P. aeruginosa) that are carriers of the ampC gene.

Methods

In this study, 105 clinical isolates of P. aeruginosa were collected. Antibiotic resistance patterns were determined using the disk diffusion method. The strains carrying AmpC enzymes were characterized by a combination disk method. Multiplex-PCR was used to identify resistance and virulence genes, chi-square test was used to determine the relationship between variables.

Results

Among 105 isolates of P. aeruginosa, the highest antibiotic resistance was to cefotaxime and aztreonam, and the least resistance was to colictin and ceftazidime. There were 49 isolates (46.66%) that showed an AmpC phenotype. In addition, the frequencies of the resistance genes were; OXA48 gene 85.2%, OXA199, 139 3.8%, OXA23 3.8%, OXA2 66.6%, OXA10 3.8%, OXA51 85.2% and OXA58 3.8%. The IMP27 gene was detected in 9 isolates (8.57%) and the IMP3.34 was detected in 11 isolates (10.47%). Other genes detected included; lasR (17.1%), lasB (18%) and lasA (26.6%). There was a significant relationship between virulence factors and the OX and IMP genes (p ≤ 0.05).

Conclusion

The relationship between antibiotic resistance and virulence factors observed in this study could play an important role in outbreaks associated with P. aeruginosa infections.

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Phenotypic Assays to Determine Virulence Factors of Uropathogenic Escherichia coli (UPEC) Isolates and their Correlation with Antibiotic Resistance Pattern: Mohsen Tabasi, Mohammad Reza Asadi Karam, Mehri Habibi, Mir Saeed Yekaninejad, Saeid Bouzari; Osong Public Health Res Perspect. 2015;6(4):261-268. Published online August 31, 2015; DOI: https://doi.org/10.1016/j.phrp.2015.08.002

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Abstract PDF

Objectives
Urinary tract infection caused by uropathogenic Escherichia coli (UPEC) strains is one of the most important infections in the world. UPEC encode widespread virulence factors closely related with pathogenesis of the bacteria. The purpose of this study was to evaluate the presence of different phenotypic virulence markers in UPEC isolates and determine their correlation with antibiotic resistance pattern.
Methods
UPEC isolates from patients with different clinical symptoms of UTI were collected and screened for biofilm and hemolysin production, mannose resistant, and mannose sensitive hemagglutination (MRHA and MSHA, respectively). In addition, antimicrobial resistance pattern and ESBL-producing isolates were recorded.
Results
Of the 156 UPEC isolates, biofilm and hemolysin formation was seen in 133 (85.3%) and 53 (34%) isolates, respectively. Moreover, 98 (62.8%) and 58 (37.2%) isolates showed the presence of Types 1 fimbriae (MSHA) and P fimbriae (MRHA), respectively. Our results also showed a relationship between biofilm formation in UPEC isolated from acute cystitis patients and recurrent UTI cases. Occurrence of UTI was dramatically correlated with the patients' profiles. We observed that the difference in antimicrobial susceptibilities of the biofilm and nonbiofilm former isolates was statistically significant. The UPEC isolates showed the highest resistance to ampicillin, tetracycline, amoxicillin, and cotrimoxazole. Moreover, 26.9% of isolates were ESBL producers.
Conclusion
This study indicated that there is a relationship between the phenotypic virulence traits of the UPEC isolates, patients' profiles, and antibiotic resistance. Detection of the phenotypic virulence factors could help to improve understanding of pathogenesis of UPEC isolates and better medical intervention.

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Antibiotic Resistance of Acinetobacter baumannii in Iran: A Systemic Review of the Published Literature: Jale Moradi, Farhad B. Hashemi, Abbas Bahador; Osong Public Health Res Perspect. 2015;6(2):79-86. Published online April 30, 2015; DOI: https://doi.org/10.1016/j.phrp.2014.12.006

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Abstract PDF

Objectives
Acinetobacter baumannii is a bacterium responsible for health care-associated infections, and it frequently develops multiple drug resistance (MDR). The prevalence of antibiotic-resistant A. baumannii in Iran has increased, and this may cause significant clinical problems. Therefore, in order to elucidate the development of antibiotic resistance, we performed a systematic review of the literature published on antibiotic-resistant A. baumannii reported in Iran.
Methods
Thirty-six publications that met the criteria for inclusion were reviewed from an initial 87 papers. Selected papers published between 2008 and September 2014, were categorized on the basis of the sample collecting year been between 2001 and 2013.
Results
Analysis of data revealed that, in general, there was an increase in antimicrobial resistance. During the initial time point of these studies (2001–2007) there was a high rate of resistance to all antibiotics, with the exception of carbapenems, lipopeptides, and aminoglycosides that had a low resistance rate in comparison with the others. Also, the resistance rate was increased in one group of these three antimicrobial groups from 2010 to 2013. In particular, there was an increase in resistance to carbapenems (imipenem and meropenem) from 2010–2011 and 2012–2013, whereas no significant change in the resistance rate of the other two antimicrobial groups (lipopeptides and aminoglycosides) during the study time was observed, although we did observe certain trends in amikacin (aminoglycoside group antibiotic) between 2011–2012 and 2012–2013.
Conclusion
These findings indicate that antimicrobial resistance of A. baumannii in Iran has increased, which may very well affect the antimicrobial resistance of this organism worldwide. Based on these results, novel prevention and treatment strategies against A. baumannii infections are warranted. Furthermore, these data may assist in revising treatment guidelines and regional policies in care units to slow the emergence of antimicrobial resistance.

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Articles

Comparison of Antimicrobial Resistance in Escherichia coli Strains Isolated From Healthy Poultry and Swine Farm Workers Using Antibiotics in Korea: Seung-Hak Cho, Yeong-Sik Lim, Yeon-Ho Kang; Osong Public Health Res Perspect. 2012;3(3):151-155. Published online June 30, 2012; DOI: https://doi.org/10.1016/j.phrp.2012.07.002

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Abstract PDF

Objectives
The aim of this study is to compare the antibiotic resistance of Escherichia coli isolates from faecal samples of workers who often use antibiotics.
Methods
A total of 163E coli strains isolated from faecal samples of livestock workers (poultry and swine farm workers) and restaurant workers in the same regions as a control group were analyzed by agar disc diffusion to determine their susceptibility patterns to 16 antimicrobial agents.
Results
Most of the tested isolates showed high antimicrobial resistance to ampicillin and tetracycline. The isolates showed higher resistance to cephalothin than other antibiotics among the cephems. Among the aminoglycosides, the resistance to gentamicin and tobramycin occurred at higher frequencies compared with resistance to amikacin and netilmicin. Our data indicated that faecal E coli isolates of livestock workers showed higher antibiotic resistances than nonlivestock workers (restaurant workers), especially cephalothin, gentamicin, and tobramycin (p < 0.05). Moreover, the rates of the livestock workers in the association of multidrug resistance were also higher than the rates of the restaurant workers.
Conclusion
This study implies that usage of antibiotics may contribute to the prevalence of antibiotic resistance in commensal E coli strains of humans.

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A diversity of Antibiotic-resistant Staphylococcus spp. in a Public Transportation System: Pamela J. Yeh, Dawn M. Simon, Jess A. Millar, H. Forrest Alexander, Darleen Franklin; Osong Public Health Res Perspect. 2011;2(3):202-209. Published online December 31, 2011; DOI: https://doi.org/10.1016/j.phrp.2011.11.047

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Abstract PDF

Objectives
Our goal was to determine the diversity and abundance of Staphylococcus bacteria on different components of a public transportation system in a mid-sized US city (Portland, Oregon) and to examine the level of drug resistance in these bacteria.
Methods
We collected 70 samples from 2 cm × 4 cm sections from seven different areas on buses and trains in Portland, USA, taking 10 samples from each area. We isolated a subset of 14 suspected Staphylococcus spp. colonies based on phenotype, and constructed a phylogeny from16S rRNA sequences to assist in identification. We used the Kirbye–Bauer disk diffusion method to determine resistance levels to six common antibiotics.
Results
We found a range of pathogenic Staphylococcus species. The mean bacterial colony counts were 97.1 on bus and train floors, 80.1 in cloth seats, 9.5 on handrails, 8.6 on seats and armrests at bus stops, 3.8 on the underside of seats, 2.2 on windows, and 1.8 on vinyl seats per 8 cm² sample area. These differences were significant (p < 0.001). Of the 14 isolates sequenced, 11 were staphylococci, and of these, five were resistant to penicillin and ampicillin, while only two displayed intermediate resistance to bacitracin. All 11 isolates were sensitive to trimethoprim-sulfamethoxazole, vancomycin, and tetracycline.
Conclusions
We found six different strains of Staphylococcus, and while there were varying levels of drug resistance, we did not find extensive levels of multidrug-resistant bacteria, and no S. aureus was found. We found floors and cloth seats to be areas on buses and trains that showed particularly high levels of bacteria.

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Original Article

Prevalence of Antibiotic Resistance in Escherichia coli Fecal Isolates From Healthy Persons and Patients With Diarrhea: Seung-Hak Cho, Yeong-Sik Lim, Mi-Sun Park, Seong-Han Kim, Yeon-Ho Kang; Osong Public Health Res Perspect. 2011;2(1):41-45. Published online June 30, 2011; DOI: https://doi.org/10.1016/j.phrp.2011.05.003

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Abstract PDF

Objectives
This study aimed to investigate the prevalence of antibiotic resistance in fecal Escherichia coli isolates from healthy persons and patients with diarrhea.
Methods
E. coli isolates (n = 428) were obtained from fecal samples of apparently healthy volunteers and hospitalized patients with diarrhea. Susceptibility patterns of isolates to 16 antimicrobial agents were determined by agar disc diffusion.
Results
Most E. coli isolates exhibited less than 10% resistance against imipenem, cefotetan, aztreonam, cefepime, cefoxitin, amikacin and netilamicin, although greater than 65% were resistant to ampicillin and tetracycline. No significant difference in resistance rates for all tested antibiotics was found between isolates from the healthy-and diarrheal-patient groups, including for multi-drug resistance (p = 0.22). The highest number of resistant antibiotics was 12 antibiotics. No significant differences in antibiotic resistance were found among the sex and age strata for isolates from healthy individuals. However, antibiotic resistance rates to cefoxitin, cefotaxime, amikacin, and netilamicin were significantly higher in the isolates of men than those of women (p < 0.05) in isolates from patients with diarrhea. Furthermore, isolates from patients with diarrhea older than 40-years of age showed higher resistance to cefepime and aztreonam (p < 0.05).
Conclusion
High resistance to the antibiotics most frequently prescribed for diarrhea was found in isolates from patients with diarrhea and apparently healthy individuals without any significant difference.

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