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Majid Ali Tahir,1,2 Mumtaz Ali Khan,3 Aamer Ikram,3 Tamoor Hamid Chaudhry,4 Aliya Jabeen,3 Abdul Quddous,3 Ijaz Ul Haq2 1Health Education Officer, CDC, National Institutes of Health, Islamabad, Pakistan; 2Department of Public Health & Nutrition, University of Haripur, Haripur, Khyber Pakhtunkhwa, Pakistan; 3Centers for Disease Control (CDC), National Institutes of Health, Islamabad, Pakistan; 4Public Health Laboratories Division, National Institutes of Health, Islamabad, PakistanCorrespondence: Majid Ali Tahir, CDC, National Institutes of Health, Islamabad, Pakistan, Email mmtahirmughal@hotmail.com; mm.tahir@nih.org.pkBackground: During outbreaks of infectious diseases like COVID-19, the healthcare-associated infections (HCAIs) pose a burden on public health system. There are very limited data about infection prevention and control (IPC) implementation in the healthcare facilities of Pakistan. The aim of the study was to conduct assessment with the IPC Assessment Framework (IPCAF) tool in healthcare facilities of the least developed areas.Methods: A cross-sectional survey was conducted in 12 tertiary level healthcare facilities (HCF) located in the least developed provinces of Pakistan. The facilities were selected through multistage cluster random methods. A well-structured questionnaire, the “IPCAF tool”, was used for data collection. The IPCAF comprises eight sections with a 100 score of each section, thus with a maximum score of 800. The scores from 0 to 800 of the HCFs were divided into four gradual ratings through IPCAF, ie from inadequate to advanced.Results: The median score of all facilities was 405, with a range from inadequate to advanced. One facility (8.3%) fell into the “inadequate” category with a score of 172.5; 5 (41.6%) facilities achieved “basic” category, another 5 (41.6%) being “intermediate”, and only one (8.3%) hospital achieved “advanced” status. Region-wise median score of facilities of GB was 307.5, facilities in AJK scored 342.5, and a score of 520 was found for health facilities in KPK. The components of Education and Training, HCAIs Surveillance, and Multimodal Strategies achieved the lowest scores.Conclusion: Most of the facilities have developed an IPC program with key focal persons and IPC committees, but did not have relevant education and training. IPC core capacities are being implemented. Equitable attention is required on all eight components of IPC in all facilities.Keywords: infection prevention and control, IPCAF, healthcare facilities, healthcare associated infections

Bilal Aslam,1 Muhammad Hussnain Siddique,2 Abu Baker Siddique,1 Muhammad Shafique,1 Saima Muzammil,1 Mohsin Khurshid,1 Muhammad Hidayat Rasool,1 Moeed Ahmad,1 Tamoor Hamid Chaudhry,3 Afreenish Amir,3 Muhammad Salman,3 Zulqarnain Baloch,4 Norah A Alturki,5 Ahmad Alzamami6 1Department of Microbiology, Government College University Faisalabad, Faisalabad, Pakistan; 2Department of Bioinformatics & Biotechnology, Government College University Faisalabad, Faisalabad, Pakistan; 3Public Health Laboratories Division, National Institute of Health, Islamabad, Pakistan; 4Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, People’s Republic of China; 5Clinical Laboratory Science Department, College of Applied Medical Science, King Saud University, Riyadh, Saudi Arabia; 6Clinical Laboratory Science Department, College of Applied Medical Science, Shaqra University, AlQuwayiyah, Saudi ArabiaCorrespondence: Bilal Aslam, Department of Microbiology, Government College University Faisalabad, Faisalabad, Pakistan, Email drbilalaslam@gcuf.edu.pk Ahmad Alzamami, Clinical Laboratory Science Department, College of Applied Medical Science, Shaqra University, AlQuwayiyah, Saudi Arabia, Email aalzamami@su.edu.saBackground: The World Health Organization (WHO) has declared the multi-drug resistant (MDR) Klebsiella pneumoniae as one of the critical bacterial pathogens. The dearth of new antibiotics and inadequate therapeutic options necessitate finding alternative options. Bacteriophages are known as enemies of bacteria and are well-recognized to fight MDR pathogens.Methods: A total of 150 samples were collected from different clinical specimens through a convenient sampling technique. Isolation, identification, and antibiotic susceptibility testing (AST) of K. pneumoniae were done by standard and validated microbiological procedures. Molecular identification of virulence factors and antibiotic resistance genes (ARGs) was carried out through polymerase chain reaction (PCR) by using specific primers. For bacteriophage isolation, hospital sewage samples were processed for phage enrichment, purification, and further characterization ie, transmission electron microscopy (TEM) and stability testing, etc. followed by evaluation of the lytic potential of the phage.Results: Overall, a total of 41% of isolates of K. pneumoniae were observed as hypervirulent K. pneumoniae (hvKp). Among hvKp, a total of 12 (42%) were detected as MDR hvKp. A total of 37% of all MDR isolates were found resistant to colistin, and 66% of the colistin resistance isolates were recorded as mcr-1 positive. Isolated phage KpnM had shown lytic activity against 53 (79%) K. pneumoniae isolates. Remarkably, all 8 mcr-1 harboring MDR hvKp and non-hvKp isolates were susceptible to KpnM phage.Conclusion: Significant distribution of mcr-1 harboring hypervirulent Klebsiella pneumoniae was observed in clinical specimens, which is worrisome for the health system of the country. Characterized phage KpnM exhibited encouraging results and showed the lytic activity against the mcr-1 harboring hvKp isolates, which may be used as a prospective alternative control strategy to fight this ominous bacterium.Keywords: Klebsiella pneumoniae, bacteriophages, colistin, MDR, virulence

Tamoor Hamid Chaudhry,1,2 Bilal Aslam,1,2 Muhammad Imran Arshad,3 Roman Farooq Alvi,2 Saima Muzammil,2 Nafeesa Yasmeen,4 Muhammad Aamir Aslam,3 Mohsin Khurshid,2 Muhammad Hidayat Rasool,2 Zulqarnain Baloch1 1Biomedical Research Center, Northwest Minzu University, Lanzhou 730030, People’s Republic of China; 2Department of Microbiology, Government College University Faisalabad, Faisalabad, Pakistan; 3Institute of Microbiology, University of Agriculture Faisalabad, Faisalabad, Pakistan; 4College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, People’s Republic of ChinaCorrespondence: Bilal Aslam; Zulqarnain Baloch Email drbilalaslam@gcuf.edu.pk; znbalooch@yahoo.comIntroduction: Intense livestock farming practices enforcing the farmers to use antibiotics as food supplements on a routine basis. Aberrant use of antibiotics is associated with the emergence of antibiotics resistance and resistant superbugs. Keeping in view the current scenario, the present study was designed for the first time from Pakistan with a specific aim to estimate the prevalence of the carbapenem-resistant Klebsiella pneumoniae in veterinary settings and the waste in Pakistan.Methods: A total of 138 samples from various veterinary sources were collected by employing a nonprobability sampling technique. Isolation and phenotypic identification of carbapenem-resistant K. pneumoniae were performed according to the CLSI standard. Molecular detection of various antibiotic resistance genes (ARGs) was done through PCR by using specific primers against each ARG. According to the pasture scheme, the multilocus sequence typing (MLST) was performed to characterize the K. pneumoniae sequence types (STs).Results: According to the results of the study, overall 9.4% (13/138) isolates were confirmed carbapenem-resistant K. pneumoniae. Among various carbapenem ARGs particularly, the blaNDM-1 was found in 92.3% (12/13) isolates followed by blaOXA-48 84.6% (11/13). MLST results revealed that overall 3 STs were found in the study which includes ST29, ST11, and ST258. Taking together, this is the first study to our best knowledge which demonstrated the prevalence of carbapenem-resistant K. pneumoniae and its various STs prevalent in veterinary settings and the waste of Pakistan.Conclusion: Based on the above-mentioned facts, we suggested that veterinary settings and waste are the potential source and reservoir of carbapenem-resistant K. pneumoniae, which may be disseminated to the environment and ultimately can affect the public and companion livestock health.Keywords: veterinary settings, carbapenem resistance, Klebsiella pneumoniae, Pakistan

Cancer is measured as a major threat to human life and is a leading cause of death. Millions of cancer patients die every year, although a burgeoning number of researchers have been making tremendous efforts to develop cancer medicine to fight against cancer. Owing to the complexity and heterogeneity of cancer, lack of ability to treat deep tumor tissues, and high toxicity to the normal cells, it complicates the therapy of cancer. However, bacterial derivative-mediated drug delivery has raised the interest of researchers in overcoming the restrictions of conventional cancer chemotherapy. In this review, we show various examples of tumor-targeting bacteria and bacterial derivatives for the delivery of anticancer drugs. This review also describes the advantages and limitations of delivering anticancer treatment drugs under regulated conditions employing these tumor-targeting bacteria and their membrane vesicles. This study highlights the substantial potential for clinical translation of bacterial-based drug carriers, improve their ability to work with other treatment modalities, and provide a more powerful, dependable, and distinctive tumor therapy., (© 2024. The Author(s).)

The uterine endometrial surface of bovines is in constant exposureconstantly exposed with to a multitude ofmany microbial populations that changes throughout the post-partum phase in terms of complexity and dynamics. These microbes contribute to the host pathology, leading to severe economic losses along withnd reproductive capabilities. The basic primary interface that occurs between the internal tissues of the body of the hostbetween the host body's internal tissues and the microbes is the endometrial surface of the uterus. As a result of the infinite pathogenic population, there is always a danger for the opportunistic organisms to attack. Therefore, it is paramount that any interactions, especially microbial microbes with the endometrial surface, are regulated by the host cells. However, the inflammatory response as the defense mechanism contributes a pivotal roleis pivotal in host immunity and pathology. The inflammatory cascade and pathways are important essential to eliminate this clinical problem. In this review, we will discuss and explain how the inflammation and the various components of the immune system play their role in host pathology and therapeutic strategies, taking into account the interface between the host and the microbes on the surface of the endometrium. This review is also instrumental in further explanation of inflammatory uterine disease by discussing the response of inflammation to external insult., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Public health emergency management systems encountered difficulties in developing countries, especially in Pakistan. The COVID-19 pandemic was extremely challenging for different agencies/departments in Pakistan. Health emergency management depends on a well-established public health emergency operations center that could generate a coordinated response to emergencies. We conducted an assessment of public health emergency response coordination implemented during the COVID-19 at strategic level. This was mix-method qualitative study. Primary data was collected by using a structured questionnaire, and secondary data was collected by desk review. The agencies engaged in pandemic response at the national level in Pakistan were included in the assessment. The overall score of the emergency response coordination system during COVID-19 was 49% for all agencies. We found that agencies faced challenges in leadership, legislation, and financing issues during the pandemic response (44%). None of the agencies had a fully developed framework for joint planning and response system for health emergencies. Roles and responsibilities attached to designated agencies in response were relatively clear (55%) for most of the agencies. Effective public health emergency response is based on multi-departmental coordination, resource mobilization, and clear roles for each agency. Pakistan must proactively address these challenges for pandemic response in future., (© 2023. The Author(s).)

Klebsiella pneumoniae is ubiquitous and known to be a notorious pathogen of humans, animals, and plant-based foods. K. pneumoniae is a recognized trafficker of antibiotic resistance genes (ARGs) between and from different ecological niches. A total of 775 samples ( n = 775) were collected from September 2017 to August 2019 from humans, animals, and environmental sources by applying the random convenient sampling technique. A total of 120 (15.7%) samples were confirmed as K. pneumoniae . The distribution of K. pneumoniae among humans, the environment, and animals was 17.1, 12.38, and 10%, respectively. Isolates have shown significant resistance against all the subjected antibiotics agents except colistin. ARGs profiling revealed that the highest percentage prevalence (67.5%) of bla CTX - M was estimated in the isolates, and various carbapenem resistance genes that were found in the study were bla NDM -1 (43.3%), bla OXA -48 (38%), and (1.67%) bla KPC -2 . Overall, 21 distinct sequence types (ST) and 13 clonal complexes (CCs) were found through the multi-locus sequence typing (MLST) analysis. Taking together, the distribution of multi-drug resistance (MDR) K. pneumoniae clones in the  community and associated environment is alarming for the health care system of the country. Health policymakers should consider the role of all the integral parts of humans, animals, and the associated environment intently to cope with this serious public and animal health concern., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Aslam, Chaudhry, Arshad, Muzammil, Siddique, Yasmeen, Khurshid, Amir, Salman, Rasool, Xia and Baloch.)

Antibiotic resistance (ABR) is a growing public health concern worldwide, and it is now regarded as a critical One Health issue. One Health's interconnected domains contribute to the emergence, evolution, and spread of antibiotic-resistant microorganisms on a local and global scale, which is a significant risk factor for global health. The persistence and spread of resistant microbial species, and the association of determinants at the human-animal-environment interface can alter microbial genomes, resulting in resistant superbugs in various niches. ABR is motivated by a well-established link between three domains: human, animal, and environmental health. As a result, addressing ABR through the One Health approach makes sense. Several countries have implemented national action plans based on the One Health approach to combat antibiotic-resistant microbes, following the Tripartite's Commitment Food and Agriculture Organization (FAO)-World Organization for Animal Health (OIE)-World Health Organization (WHO) guidelines. The ABR has been identified as a global health concern, and efforts are being made to mitigate this global health threat. To summarize, global interdisciplinary and unified approaches based on One Health principles are required to limit the ABR dissemination cycle, raise awareness and education about antibiotic use, and promote policy, advocacy, and antimicrobial stewardship., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Aslam, Khurshid, Arshad, Muzammil, Rasool, Yasmeen, Shah, Chaudhry, Rasool, Shahid, Xueshan and Baloch.)

Combinations of two and more drugs with different target sites are being used as a new treatment regimen for resistant clones of bacteria. Though, achieving the right combination of the drugs for optimal dosage regimen is challenging. In our study, we studied the antimicrobial effect of aditoprim, a novel dihydrofolate reductase inhibitor, and its synergistic effect with sulfamethoxazole. Synergy testing was performed by checkerboard micro dilution method and validation of different checkerboard ratios by static and dynamic time-kill analysis and in vitro pharmacokinetic/pharmacodynamics (PK/PD) model, and semi mechanistic PK/PD modeling was used to calculate and validate the synergistic effect of drug combination. Both checkerboard and static time-kill assays demonstrated the greater synergistic effect [fractional inhibitory concentration index (FICI) = 0.37] of the aditoprim [minimum inhibitory concentration (MIC) = 0.25 µg/ml]-sulfamethoxazole (MIC=>64 µg/ml) combination against all T. Pyogenes isolates. In the in vitro PK/PD model, the dosage proportion of sulfamethoxazole 4 mg/ml twice a day in combination with steady-state aditoprim 1 mg/ml efficiently repressed the growth of bacteria in 24 h with the ratio of 2-log10 decrease, related to the early inoculum against three T. Pyogenes isolates. The semi mechanistic PK/PD model projected that a combination of a high dose of aditoprim (2 mg/ml) with sulfamethoxazole (2 mg/day) was necessary to attain the killing of bacteria below the detection limit (limit of detection (LOD); i.e., 1 log10 CFU/ml) at 24 h with an MIC sulfamethoxazole (SMZ) of 64 µg/ml. However, it is anticipated that a combination of high dose of aditoprim with sulfamethoxazole is critical to attain the suppressed bacterial growth to < LOD. This study represents essential PK/PD modeling for optimization of combination of aditoprim and sulfamethoxazole to suppress growth of T. Pyogenens ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Maan, Chaudhry, Sattar, Shabbir, Ahmed, Mi, Ahmed, Xie, Xin and Huang.)

Since the end of 2019, the emergence of novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has accelerated the research on host immune responses toward the coronaviruses. When there is no approved drug or vaccine to use against these culprits, host immunity is the major strategy to fight such infections. Type I interferons are an integral part of the host innate immune system and define one of the first lines of innate immune defense against viral infections. The in vitro antiviral role of type I IFNs against Middle East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV (severe acute respiratory syndrome coronavirus) is well established. Moreover, the involvement of type I IFNs in disease pathology has also been reported. In this study, we have reviewed the protective and the immunopathogenic role of type I IFNs in the pathogenesis of MERS-CoV, SARS-CoV, and SARS-CoV-2. This review will also enlighten the potential implications of type I IFNs for the treatment of COVID-19 when used in combination with IFN- γ .

Introduction: Intense livestock farming practices enforcing the farmers to use antibiotics as food supplements on a routine basis. Aberrant use of antibiotics is associated with the emergence of antibiotics resistance and resistant superbugs. Keeping in view the current scenario, the present study was designed for the first time from Pakistan with a specific aim to estimate the prevalence of the carbapenem-resistant Klebsiella pneumoniae in veterinary settings and the waste in Pakistan., Methods: A total of 138 samples from various veterinary sources were collected by employing a nonprobability sampling technique. Isolation and phenotypic identification of carbapenem-resistant K. pneumoniae were performed according to the CLSI standard. Molecular detection of various antibiotic resistance genes (ARGs) was done through PCR by using specific primers against each ARG. According to the pasture scheme, the multilocus sequence typing (MLST) was performed to characterize the K. pneumoniae sequence types (STs)., Results: According to the results of the study, overall 9.4% (13/138) isolates were confirmed carbapenem-resistant K. pneumoniae . Among various carbapenem ARGs particularly, the bla NDM-1 was found in 92.3% (12/13) isolates followed by bla OXA-48 84.6% (11/13). MLST results revealed that overall 3 STs were found in the study which includes ST29, ST11, and ST258. Taking together, this is the first study to our best knowledge which demonstrated the prevalence of carbapenem-resistant K. pneumoniae and its various STs prevalent in veterinary settings and the waste of Pakistan., Conclusion: Based on the above-mentioned facts, we suggested that veterinary settings and waste are the potential source and reservoir of carbapenem-resistant K. pneumoniae , which may be disseminated to the environment and ultimately can affect the public and companion livestock health., Competing Interests: The authors have no conflicts of interest to declare for this work., (© 2020 Chaudhry et al.)

Klebsiella pneumoniae is an important pathogen that causes pneumonia and bloodstream infections, especially in neonates and intensive care patients. The carbapenems remain an important therapeutic option for clinicians, particularly against cephalosporin-resistant Gram-negative pathogens. This increased use of carbapenems at clinics has resulted in the evolution and spread of carbapenem-resistant K. pneumoniae . In this study, we isolated six bla K. pneumoniae carbapenemase (KPC)-producing strains belonging to sequence type 258 (ST258) from clinical, environmental, and veterinary sources. Antibiotic susceptibility was performed on these isolates and the genes responsible for extended-spectrum beta-lactamases and metallo-beta-lactamase production were screened. The molecular typing was done using multilocus sequence typing. Isolated strains were resistant to various antibiotic classes, including carbapenems, and carried the carbapenem-resistant gene, blaKPC. All strains were susceptible to tigecycline and colistin. This is the first report detecting K. pneumoniae ST258 strains in Pakistan.

Presence of multiple drug resistant pathogens in hospital waste is a serious public health concern, because it may ultimately be disseminated to the human. Current study was designed with the objective to estimate the occurrence of ESBL-producing K. pneumoniae in hospital settings and waste. For this purpose, cross sectional study for a period of one year was designed and non-probability sampling techniques was used to collect total n=112 samples from various sample sources of hospital waste including ward waste, operation theatre waste, wastewater and hospital sludge. Isolation of the K. pneumoniae was done by using selective agar, biochemical identification of the isolates was done through API 20E kit (bioMérieux, France). Molecular identification of the isolates was done by amplifying 16SrDNA with PCR. According to CLSI guidelines disc diffusion assay was performed for antibiotic susceptibility profiling. PCR of MDR isolates was done for the molecular detection of various ESBL genes. Results of the study showed 17 (15%) percentage prevalence of MDR K. pneumoniae from all 112 collected samples. Among various sample sources wastewater showed the highest percentage (23%) prevalence of MDR K. pneumoniae. In 17 confirmed isolates bla CTX-M and blaCTX-M1 were found in 13 (76%) and 12 (71%) respectively which showed the highest prevalence as compared to all other investigated genes. While bla TEM , bla SHV , bla NDM-1 and bla OXA-48 were found with percentage prevalence 9 (53 %), 1 (6%), 9 (53%) and 6 (35 %) respectively. Whereas bla KPC , bla IMP , bla VIM and bla GIM were not detected in any of the isolate. Taking together, strict rules and regulations should be adopted at public as well as hospital level to restrict the dissemination of antibiotic resistance from hospital environment to humans.