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Acinetobacter baumannii is an opportunistic bacterial pathogen that causes severe infections in immunocompromised individuals. A. baumannii forms biofilm and produces extracellular matrix, which supports bacteria to survive under harsh conditions and be resistant to antibacterial treatments. In the present study, we investigated the biofilm and quorum-sensing inhibitory effects of antimicrobial peptide, octopromycin in A. baumannii. Field emission-scanning electron microscopy results clearly showed significantly reduced biofilm mass and caused a collapse in biofilm architecture at the minimum inhibitory concentration (50 µg/mL) and minimum bactericidal concentration (200 µg/mL) of octopromycin. Antibiotic-resistant persister cells of A. baumannii were successfully killed by octopromycin treatment, and it inhibited violacein production in Chromobacterium violaceum in a concentration-dependent manner. Octopromycin also inhibited alginate production, surface movements (swarming and swimming), and twitching motility of A. baumannnii, confirming its anti-quorum-sensing activity. Multiple metabolic pathways, two-component regulation systems, quorum-sensing, and antibiotic synthesis-related pathways in A. baumannii biofilms were strongly affected by octopromycin treatment. The collective findings indicate that the antibacterial peptide octopromycin may control A. baumannii biofilms through multi-target interactions. Octopromycin could be a desirable therapeutic option for the prevention and control of A. baumannii infections.

Rapid and accurate detection performs an important role in the control of raising MDR-TB. Currently, studies on biomarkers as targets for TB diagnostic tests using immune response products to indicate the presence, mycobacterial load, early markers, and activity, diff erentiation, and progression markers of TB infection are rapidly available. This systematic review aims to summarize the last fi ve years of potential biomarkers studies from the immune response for MDR-TB rapid diagnostic development. The authors performed a literature search on four databases as ProQuest, EBSCO Academic Search, Universitas Gadjah Mada Online Library Journal Database, and Google Scholar, retrieved from January 2016 to December 2021. In total, 18,288 articles were identifi ed and three tudies met the inclusion criteria. Several promising biomarkers were found for MDR-TB diagnosis purposes, such as sCD14, PGLYRP2, FGA, Indoleamine 2, 3- dioxygenase (IDO), and Complement Receptor 2 (CR2). A combination of sCD14, PGLYRP2, and FGA were bringing a diagnostic design with a higher sensitivity (94.7%) and specifi city (80%) than the design of a single protein. Higher IDO activity towards the MDR-TB group than in the DS-TB group with a sensitivity of 87.50 %, specifi city of 72.22 %. CR2 was the main focus due to its association with IL-6. After induction of CR2 peptide in a dose-dependent manner, the expression level of IL-6 was decreased signifi cantly. It might because of CR2 peptide regulating the macrophages proinfl ammatory cytokines secretion to decrease the local infl ammation of the immune response. These biomarkers are strong candidates for MDR-TB diagnosis due to their important role as the pathogenesis marker of MDR-TB. There is a need of further research to investigate those immune response products and their role to eliminate infection of Mycobacterium tuberculosis directly.

Transplant recipients are highly susceptible to multidrug-resistant (MDR) related infections. The lack of early appropriate antimicrobial treatment may contribute to the high mortality due to MDR-related infections in transplant recipients especially in case of metallo-β-lactamases.In this review, we present the current state of knowledge concerning multidrug-resistant Gram negative bacilli's risk management in the care of solid-organ transplant recipients and suggest control strategies.We searched for studies treating MDR g-negative bacilli related infections in the renal and hepatic transplant patient population. We included randomized and observational studies.Solid-organ transplant is the best therapeutic option for patients diagnosed with end-stage organ disease. While the incidence of opportunistic infections is decreasing due to better prevention, the burden of "classical" infections related to MDR bacteria especially related to Gram-negative bacteria is constantly increasing. Over the last two decades, various MDR pathogens have emerged as a relevant cause of infection in this specific population associated with significant mortality. Several factors related to the management of transplant donor candidates and recipients increase the risk of MDR infections in transplant recipients. The awareness of this high susceptibility of transplant recipients to MDR-related infections challenges the choice of empirical therapy, while its appropriateness can only be validated a posteriori. Indeed, the lack of early appropriate antimicrobial treatment may contribute to the high mortality due to MDR-related infections in transplant recipients especially in case of metallo-β-lactamases.Multidrug-resistant Gram-negative bacteria are associated with high morbidity and mortality in solid organ transplant recipients. It seems important to identify patients at risk of colonization/MDR bacteria to evaluate strategies to limit the risk of secondary infections and to minimize the inappropriate use of broad-spectrum antibiotics.

Background Microbial infections together with rising drug resistance pose a threat to immunocompromised individual. In this perspective, compounds with spirooxindolopyrrolidine play a significant role in research on antimicrobial drug delivery research owing to their various pharmaceutical activities. Spiroheterocyclic compounds are present in number of medications as active motif due to their exceptional structural properties which enable for easy interaction with the protein of the biological target. Inspired by this biological precedent encouraged to synthesize a new class of dispirooxindole fused pyrrolidine heterocycles via a three-component cycloaddition strategy. Materials and Methods The new class of structurally intriguing spirooxindolopyrrolidines were synthesized through three component cycloaddition process and the structure of products were assigned through spectroscopic analysis. The newly synthesized compounds were assessed for their antimicrobial sensitivity test with standard Kirby Bauer method with common drugs. Results The structurally unexplored hybrid heterocycles fused spirooxindolopyrrolidine exhibited excellent antimicrobial activity against the common nosocomial microbial pathogens. Of four compounds, the compound bearing a chlorine atom on the aryl ring (4a) exhibited significant antimicrobial activity (zone of inhibition: 9.00 ± 1.00–17.00 ± 0.35 mm and MIC: 16.00–256.00 μg/mL) against selected nosocomial infection causing microbial pathogens. Hence, the compound 4a has been considered as an effective drug of interest in therapeutic field for compacting infectious diseases causing pathogens. Conclusion With an aim of developing more effective and economically more affordable antimicrobial leads with a unique mechanism of action, we have designed and synthesized structurally diverse spirooxindolopyrrolidine tethered hybrids that has been assayed against multidrug resistant nosocomial pathogens. The regioisomer having chloro substituted on the phenyl ring showed potent activity when compared to standard drug. Future studies are required to explicate the pharmacological properties of new hybrid heterocycles that have been synthesized in our laboratory for the novel therapeutic development.

Background Staphylococcus aureus infection is associated with hospitals and caused mortality in hospitalized patients. These biofilm-forming bacteria are associated with chronic infections in patients. Objectives To investigate the biofilm forming ability of multidrug resistant bacteria associated with hospital environment and analyze anti-biofilm compounds from the natural sources. Methods The hospital wastewater sample was used for the isolation of drug resistant S. aureus strains. The biofilm producing ability was analyzed and the isolated S. aureus strains were tested for antibiotic susceptibility patterns against various antibiotics. To screen suitable antibacterial agent, essential oil was extracted from Teucrium polium by hydrodistillation method and the compounds were determined by GC–MS analysis. The antimicrobial potential of essential oil was studied against S. aureus strains by disc diffusion method and biofilm inhibition property of essential oil was analyzed. The synergistic activity of essential oil was also analyzed. Results A total of 13 S. aureus strains were isolated and almost all bacterial strains showed biofilm forming ability. Most of the isolated S. aureus strains showed resistance to ampicillin, cefoxitin, ciprofloxacin, erythromycin, gentamicin, chloramphenicol and vancomycin. The extracted essential oil showed pale yellow in colour with pleasant odour and the yield was about 0.9%. Twenty-two compounds were detected in GC–MS analysis which shared about 96% of the total determined chemical composition. The major compounds determined were α-pinene (5.3%), linalool (16.2%), caryophyllene (10.04%), germacrene D (37.2%), and β-eudesmol (6.1%). The extracted essential oil showed antibacterial activity and the zone of inhibition varied from 15 ± 1 to 21 ± 2 mm against S. aureus strains. The essential oil showed antibiofilm activity and synergistic activity against S. aureus strains. Conclusions This study analyzed biofilm forming ability of drug resistant S. aureus strains isolated from the hospital wastewater. The isolated bacterial strains showed resistance against various tested antibiotics. The essential oil extracted from T. polium showed antibacterial and anti-biofilm activity.

To develop novel antimicrobial agents, and based on the biologically active heterocyclic quinoline and thiazole substituted, a series of novel α-aminophosphonates (9a–h) and (10i–l) derivatives that incorporated quinoline or quinolone, and coumarylthiazole or 5-phenylthiazol-2-amine moieties were designed and synthesized via Kabachnik–Fields reaction in the presence of ionic liquid under ultrasound irradiation. All the new compounds were obtained in good yield with a simple workup and were confirmed using various spectroscopic methods. The in vitro antimicrobial activity of all synthesized compounds were screened in terms of MIC values against the selected strains of Gram-negative and Gram-positive bacteria and two fungal strains using the broth micro-dilution method. The results showed that most of the tested compounds showed moderate inhibitory activities against both Gram‐positive and ‐negative bacteria compared with reference drugs. The following compounds 9e, 9g, 9h, 9i and 9f, 9g, 9h, 10k, 10l are the most active against Gram-positive and Gram-negative bacteria strains, respectively, with MIC values ranging between 0.25 and 128 μg/mL. The synthesized compounds 9b, 9c, 9f, 9g, 9h, 10k, and 10l exhibited excellent antifungal inhibition with MIC values ranging between 0.25 and 32 μg/mL. Structure–activity relationship revealed that the presence of coumarylthiazole moiety and hydroxyl in the quinoline group increased the inhibitory activity against microbial strains pathogens. These results confirm that the synthesized compounds can be potential antimicrobial drugs candidate.

Aim: multidrug-resistant (MDR) tuberculosis (TB) and drug-sensitive-TB have long treatment periods which affect patient compliance and treatment outcomes. We planned to determine the factors that will affect the management of this disease in the elderly population. Methods: in a period of two years, a total of 82 elderly patients with bacteriologically proven TB enrolled into our retrospective study between 2011-2018. The patients' demographic features, laboratory findings, and hospital records were analyzed. Results: we enrolled 67 (87.7%) patients with drug-sensitive TB and 15 (18.2%) MDR-TB in our study. In the study population, 73.2% (n=60) were male and the mean age was 75 +/- 9 years. When we compare treatment complications of MDR-TB and drug-sensitive-TB, we found out the rate of electrolyte imbalance, nephrotoxicity, and ocular toxicity more common among the MDR-TB group (p=0.008, p=0.008, and p=0.032, respectively). When we compare the mortality rate, cure, and treatment success between MDR-TB and drug sensitive TB, there were no statistically significant results (p=0.898, p=0.549, p=0.488; respectively). Conclusion: however, we think that this was due to the low sample size. Nevertheless, we should be careful in terms of complications management of the geriatric population., NA

Background: Tuberculosis [TB] and hepatitis C virus [HCV] infections are both common infectious diseases. Although HCV infection is frequent in patients with TB, few studies have been conducted worldwide and there is still little evidence concerning this topic.Aim of the work: To assess the prevalence of HCV infection among tuberculous patients and to investigate its impact on tuberculosis and its treatment outcome.Patients and Methods: A cross-sectional study was done on 500 tuberculous patients. Socio-demographic data, clinical history and examination, clinical severity, response to drugs, laboratory and radiological investigation, Tuberculin skin test, and HCV screening were done.Results: HCV infection was detected among 54 tuberculosis patients [10.8%]. HCV- positive patients suffered more from almost all clinical presentation than HCV- negative patients but without statistical significant difference. Tuberculin skin test induration and reactions were more in HCV- negative patients with 17.9 ± 4.9 mm compared to 12.9 ± 2 mm in HCV- positive patients. Lung cavitation and lung infiltration were the most predominant radiological finding among HCV- positive patients. CAT [category] IV and modified CAT I were the most treatment regimen used in HCV- positive patients. Failure of treatment was significantly higher among HCV- positive patients [59.3%] compared to 9.9% of their counterparts. Moreover, multidrug resistance [MDR] and rifampicin resistance were significantly higher in HCV- positive group than their comparable group [31.5% and 29.6%, and 9% and 4.3% respectively].Conclusion: Co-infection of HCV in Patients with TB is frequent. It increases the frequency of almost all clinical presentation and had its predominant findings on laboratory and radiological investigations. Co-infection also alters the response to TB treatment and should be screened among tuberculous patients before treatment and closely monitored during treatment to detect early any drug resistance or treatment failure.

Yunying Wang,1 Hui Liu,2 Lijun Zhang,1 Bin Sun1 1Department of Laboratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Blood Transfusion, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Bin SunDepartment of Laboratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, No. 74 Linjiang Road, Yuzhong District, Chongqing, People’s Republic of ChinaTel +86 23-62887812Fax +86 23-63703244Email sunbin@cqmu.edu.cnPurpose: Infection and transmission of carbapenem-resistant Aeromonas is a serious threat to public health. Rapid and accurate detection carbapenem-resistant of these organisms is essential for reasonable treatment and infection control. This study aimed to find a simple and effective method to detect carbapenem-resistant phenotype in Aeromonas.Methods: A total of 131 clinical preserved Aeromonas strains were used in this study. The carbapenemase genes were detected by PCR. Modified carbapenem inactivation method (mCIM) in conjunction with EDTA-modified carbapenem inactivation method (eCIM) and simplified carbapenem inactivation method (sCIM) were performed to detect carbapenemases. We also designed a simple method, carbapenem inactivation method using supernatant (CIM-s), to detect the carbapenemase activity in the medium.Results: Of the 131 Aeromonas strains, 79 contained carbapenemase genes, including 68 blaCphA, 6 blaKPC-2, 2 blaNDM-1 and 3 blaKPC-2+CphA. However, routine antibiotic susceptibility testing could not completely identify carbapenemase-producing Aeromonas. In phenotypic assays, the sensitivity and specificity of mCIM were 100%. The combined mCIM and eCIM could distinguish serine carbapenemase and metallo-β-carbapenemases except co-producing organisms. The sensitivity and specificity of sCIM were 92.4% and 100%, respectively, which could not detect CphA totally. CIM-s results indicate that these carbapenemases could secrete into the medium to perform their hydrolytic activities and had a sensitivity and specificity of 97.5% and 100%, respectively.Conclusion: The combination of mCIM and eCIM can effectively detect and distinguish different types of carbapenemase in Aeromonas, and could be used as an important supplement approach to the antibiotic susceptibility testing.Keywords: Aeromonas, modified carbapenem inactivation method, carbapenemase, multidrug resistant, phenotypic detection

Aquaculture is one of the sectors of animal husbandry with the fastest growth rate. However, the increase in the sector's production chain without proper management can result in factors that favor the development of diseases, especially infectious diseases caused by bacteria. Many factors, such as agriculture or industry resides, improper use of antibiotics in animals or humans, have contributed to increased environmental pressure and the appearance of antibiotic-resistant bacteria, while residues from these drugs can remain in the carcasses and in water a risk to public and environmental health. From that, we identified the bacterial genus/species and their bacterial resistance to antibiotics from samples received from fish disease outbreaks for bacteriosis diagnosis between January 2017 and October 2020. Isolated bacteria were subjected to the Kirby and Bauer sensitivity test for five classes of antibiotics (penicillins, fluoroquinolones, aminoglycosides, amphenicols, and tetracyclines). Of the 181 analyzed outbreaks, 232 bacteria were isolated, including Streptococcus spp., Aeromonas spp., Edwardsiella spp., Plesiomonas shigelloides, Pseudomonas aeruginosa, Chromobacterium violaceum, Flavobacterium spp., Citrobacter spp., Enterococcus spp., Vibrio spp., Enterobacter spp., Chryseobacterium meningosepticum. Of the 232 bacteria, 40 strains were classified as multidrug resistant (MDR), with Plesiomonas shigelloides, Aeromonas spp., and Edwardsiella spp. representing more than half of this number (22/total). With several bacteria demonstrating resistance to Brazilian aquaculture-legalized drugs (tetracycline and florfenicol), it is mandatory to research, not only for alternatives to the use of antibiotics, but also for other drugs effective against the main circulating bacterial pathogens. In addition, vigilance over the occurrence of resistant bacteria is necessary, considering the appearance of zoonotic bacteria with multi-resistant characteristics, becoming a public health concern. Aquicultura é um dos setores da produção animal com o mais rápido crescimento. Muitos fatores, como resíduos industriais e/ou de agricultura e o uso indevido de antibióticos em animais ou humanos têm contribuído para aumentar a pressão ambiental e o aparecimento de bactérias resistentes a antibióticos contribuindo para os resíduos dessas drogas permanecerem nas carcaças e na água, o que é um risco para a saúde pública / ambiental. A partir disso, foram identificados o gênero / espécie de bactérias e sua resistência bacteriana aos antibióticos de amostras recebidas de surtos de doenças em peixes para diagnóstico bacteriológico no período entre janeiro de 2017 e outubro de 2020. As bactérias isoladas foram submetidas ao teste de sensibilidade de Kirby e Bauer para cinco classes de antibióticos (penicilinas, fluoroquinolonas, aminoglicosídeos, anfenicóis e tetraciclinas). Nos 181 surtos analisados, 232 bactérias foram isoladas, sendo estas Streptococcus spp., Aeromonas spp., Edwardsiella spp., Plesiomonas shigelloides, Pseudomonas aeruginosa, Chromobacterium violaceum, Flavobacterium spp., Citrobacter spp., Enterococcus spp., Vibrio spp., Enterobacter spp., Chryseobacterium meningosepticum dentre outras. Destas 232 bactérias, 40 cepas foram classificadas como multirresistentes (MDR), com Plesiomonas shigelloides, Aeromonas spp. e Edwardsiella spp. representando mais da metade destas (22 / total). Com várias bactérias demonstrando resistência aos medicamentos legalizados na aquicultura brasileira (tetraciclina e florfenicol), torna-se obrigatória a pesquisa, não apenas de alternativas ao uso de antibióticos, mas também de outros medicamentos eficazes contra os principais patógenos circulantes. Além disso, a vigilância sobre a ocorrência de cepas resistentes é necessária levando-se em consideração o aparecimento de bactérias zoonóticas com essa característica, tornando-se um ponto de interesse à saúde pública.

Objective An ambulance is a medically equipped vehicle which is used in case of any medical emergency for the transport of patients to treatment facilities. The ambulances help in the transportation of thousands of patients per year, and such patients may carry infectious microorganisms which pose a major threat to the treatment of such patients. In this study, we analyzed the extent of bacterial contamination in our ambulance vehicles and measured the degree of antimicrobial resistance among isolated pathogens. Material and Method This study included five ambulances of our tertiary care hospital and different random sites were swabbed in each vehicle. These were selected based on their well-known high frequency of contact by emergency personnel and patients. Swabs were inserted into sterile test tubes containing normal saline and immediately transferred to our microbiology laboratory to identify bacterial contaminants utilizing standard microbiological procedures. Result A total of 198 swab samples were collected from all the five ambulances, out of which 170 (85.8%) swabs were sterile and 28 (14.2%) swabs yielded potentially pathogenic bacterial isolates. The highest contamination rate with pathogenic bacteria was detected in the oxygen flow meter knob (60%), suction machine tubing (60%), and stethoscope (40%). Staphylococcus aureus (32%) was the most frequently detected microorganism. Conclusion Our study showed low prevalence of bacterial contamination in ambulances because of good infection control policy of our hospital, however, some areas still need improvement and require proper standard operating procedures of disinfection policies of these emergency vehicles.

Elizabethkingia is ubiquitary aerobic bacillus abundantly found in the community as well as hospital environments. Elizabethkingia meningoseptica is an emerging nosocomial pathogen with an elemental ability to acclimate and survive in diversified environmental circumstances. Prompt diagnosis and an early therapeutic intervention are preponderant in the management of these infections. We report a case of meningitis with septicemia caused by E. meningoseptica in a 1-day-old outborn neonate. The child was stabilized with anticonvulsants and, based on laboratory findings, the neonate was started on ciprofloxacin in addition to symptomatic management. The child responded well to the treatment and was discharged on day 7 after treatment initiation. Perceptive treatment protocols backed with accurate laboratory evidence remain instrumental to avert unpropitious outcomes while combatting rare multidrug-resistant opportunistic infections.

Background: Gastrointestinal carriage of multidrug resistant (MDR) Gram-negative bacilli, especially Klebsiella pneumoniae and Escherichia coli, was highly associated with severe nosocomial infections. The main objectives of this study were to determine the clonal relatedness of intestinal carriage and transmission risk factors of MDR E. coli and K. pneumoniae amongst preterm infants admitted to the neonatal intensive care unit (NICU). Methods: A prospective cohort study of preterm infants with gestational age

Background Urinary tract infections (UTIs) are common in dogs and can be caused by multidrug‐resistant Escherichia coli (E coli). Objective To describe the frequency and mechanisms of antimicrobial resistance (AMR) among E coli causing UTIs in dogs in Western Canada during a 4‐year surveillance period. Animals Urine from 516 dogs. Methods From November 2014 to 2018, 516 nonduplicate E coli isolates from the urine of dogs were collected from a diagnostic laboratory. Susceptibility testing was determined for a panel of 14 antimicrobials belonging to 7 drug classes. Resistant isolates were screened for the presence of extended‐spectrum beta‐lactamases (ESBLs), AmpC β‐lactamases, and plasmid‐mediated quinolone resistance (PMQR) genes. Epidemiological relationships were assessed by MLST. Results 80.2% (414/516) of isolates were susceptible to all antimicrobials tested. There was no significant increase in the proportion of isolates resistant to any of the tested antimicrobials during the study period. Resistance to ampicillin was the most common (14.9%, 77/516). Overall, 12 isolates had bla CMY‐2‐type AmpC β‐lactamases, and 7 produced CTX‐M‐type ESBLs. A single isolate had the aac(6′)‐Ib‐cr PMQR gene. The qnr and qepA determinants were not detected. A single isolate belonging to the pandemic lineage ST131 was identified. Conclusion Escherichia coli isolated from the urine of dogs in our region remain susceptible to first‐line therapies, though resistance, particularly to the aminopenicillins, warrants monitoring. This is the first description of E coli ST131 from a companion animal in Canada.

We describe rapid spread of multidrug-resistant gram-negative bacteria among patients in dedicated coronavirus disease care units in a hospital in Maryland, USA, during May–June 2020. Critical illness, high antibiotic use, double occupancy of single rooms, and modified infection prevention practices were key contributing factors. Surveillance culturing aided in outbreak recognition and control.

The aim of the current research was to isolate and purify antimicrobial cationic peptides (Amps) taken from camel blood and to study its antibacterial activity against some multidrug-resistant pathogenic bacteria Salmonella typhimurium, Bacillus subtilis. The results showed the possibility of obtaining these peptides from camel's white blood cells, and was separated by using Reversed-Phased-High Performance Liquid Chromatography (RP-HPLC) technical equipment. The results showed the presence of 21 absorption peaks of the isolated peptide extract. The two-stage-radial diffusions method was used to study the activity of the crude peptide against the studied bacteria. The results showed that these peptides were effective without any resistance. The best effect was on the Bacillus subtilis with a diameter of 31 mm inhibition, while the less effect was on the Salmonella typhimurium with a diameter of 20 mm.

Background: Sparse published data are available from Andhra Pradesh the burden of multidrug-resistant (MDR) Gram-negative bacteria in clinical specimens. Methods: We studied the burden of MDR Gram-negative bacteria from among various clinical specimens in our tertiary care teaching institute. Results: A total of 6900 isolates were obtained of which 2960 organisms were MDR. Escherichia coli were the most frequently isolated Gram-negative species (37%), followed by Klebsiella spp. (13.4%). Pseudomonas aeruginosa, Acinetobacter spp. and Enterobacter spp. were the other commonly isolated Gram-negative organisms. High resistance rates were observed for all antimicrobials studied except for cefoperazone-sulbactam (62.6%), meropenem (70%), aminoglycosides (64%) and polymyxin B (98.6%). In spite of high resistant rates (>50%) for ciprofloxacin (80%), cephalosporins (74.4%) and cotrimoxazole (65.7%), the above-mentioned antimicrobials were clinically effective. Extended-spectrum β-lactamase production was one of the significant mechanisms of resistance in our study as β-lactam resistance was 74.4%. Conclusions: Our study documents a high proportion of resistant Gram-negative organism isolates. Clinicians should consider this while initiating antibiotic treatment.

Background At the end of 2018, South Africa updated its all-oral regimen, to include bedaquiline (BDQ) and 2 months of linezolid (LZD) for all patients initiating the shorter 9–12 months regimen for rifampicin-resistant tuberculosis (RR-TB). We assessed a group of patients in rural KwaZulu-Natal for safety and effectiveness of this treatment regimen under programmatic conditions. Methods We conducted a retrospective cohort analysis on RR-TB patients treated with a standardized all-oral short regimen between 1 July 2018 and 30 April 2019 in 3 facilities in King Cetshwayo District. An electronic register (EDR web) and facility-based clinical charts were used to collect variables, which were entered into an Epi-Info database. Results Our cohort included 117 patients; 68.4% (95% confidence interval [CI]: 59.3–76.3) tested positive for human immunodeficiency virus (HIV). The median time to culture conversion was 56 days (95% CI: 50–57). Treatment success was achieved in 75.2% (95% CI: 66.5–82.3) of patients. Mortality within the cohort was 12.8% (95% CI: 7.8–20.3). Anemia was the most frequent severe adverse event (AE). The median time to develop severe anemia was 7.1 weeks (interquartile range [IQR] 4.0–12.9) after treatment initiation. LZD was interrupted in 25.2% (95% CI: 17.8–34.5) of participants. Conclusions An all-oral shorter regimen, including BDQ and LZD as core drugs for the treatment of RR-TB, shows good outcomes, in a high HIV burden rural setting. AEs are common, especially for LZD, but could be managed in the program setting. Support is needed when introducing new regimens to train staff in the monitoring, management, and reporting of AEs., An all-oral regimen, combining linezolid and bedaquiline, for the treatment of rifampicin-resistant tuberculosis shows good outcomes, irrespective of human immunodeficiency virus (HIV) status or CD4 level. Linezolid accounted for nearly half of severe adverse events and warrants close monitoring for myelosuppression and neuropathy.

Cervical‐TB lymphadenitis is the most frequent extrapulmonary manifestation of tuberculosis infection. There are limited documents (only five documents) on multidrug‐resistant cervical tubercular lymphadenitis, but there is no evidence for MDR‐cervical tuberculosis lymphadenitis in infants, which may occur in TB endemic regions.

Hospital-acquired bloodstream infections (BSIs) cause high mortality in the intensive care units (ICUs) compared to wards. Furthermore, the isolation of multidrug resistant (MDR) organisms in ICUs add to the gravity of the condition making the treatment a bigger challenge. The present study was aimed to evaluate the prevalence, spread, and the possible MDR organisms contributing to ICU-acquired BSI & the source of the secondary BSI in the ICUs. A prospective study was conducted in four ICU of tertiary teaching hospital over a period of six months. Patient that developed features of BSI within 48 hours after hospital admission were included in the present study Blood culture was performed by an automated BacT/ALERT®3D system. The source of secondary BSI was identified by analysing culture results for the samples other than blood. These samples were taken within 48 hours of the patient’s blood culture test being positive. A total of 50 patients (25%) had an ICU acquired bloodstream infection. Out of 50 patients, 74% of them had bacterial etiology. Thirty one patients (62%) among them developed multidrug resistant bacteraemia. Fifty six percent of Gram negative bacilli were multi drug resistant. The resistance to carbapenem was 42%. The most common MDR Gram negative isolate was identified as Klebsiella pneumoniae (n=12; 38.7%,) and the most common source was pulmonary infection (26.7% (n=12). 42% of isolates in our study were carbapenem resistant suggesting the need for a proper antibiotic policy in the ICUs. Prolonged stay in the ICU with mechanical ventilation was the critical risk factor and ICU mortality was high (38%).

In this study, two lytic bacteriophages designated as vB_CjP and vB_CcM were isolated and evaluated for their ability to combat multidrug-resistant bacteria Campylobacter jejuni and Campylobacter coli, respectively. A morphological analysis of these phages by transmission electron microscopy revealed that the vB-CjP bacteriophage had a mean head dimension of 66.6 ± 2.1 nm and a short non-contractile tail and belongs to the Podoviridae family, whereas vB_CcM had a mean head dimension of 80 ± 3.2 nm, a contractile tail, and a length calculated to be 60 ± 2.5 nm and belongs to the Myoviridae family. The results of the host range assay showed that vB_CjP could infect 5 of 10 C. jejuni isolates, whereas vB_CcM could infect 4 of 10 C. coli isolates. Both phages were thermostable and did not lose their infectivity and ability to lyse their host following exposure to 60 °C for 10 min; furthermore, phage particles were relatively stable within a pH range of 6–8. A one-step growth curve indicated that the phages produced estimated burst sizes of 110 and 120 PFU per infected cell with latent periods of 10 and 15 min, for vB-CjP and vB-CcM, respectively. The lytic activity of these phages against planktonic Campylobacter showed that these phages were able to control the growth of Campylobacter in vitro. These results suggest that these phages have a high potential for phage applications and can reduce significantly the counts of Campylobacter spp. The lytic activity of vB-CjP and vB-CcM phages at different (MOIs) against multidrug resistance Campylobacter strains was evaluated. The bacterial growth was slightly delayed by both phages, and the highest efficiency of both phages was observed when MOI = 1 was applied.

Ellipticine is an indole alkaloid with proven antitumor activity against various tumors in vitro and a diverse mechanism of action, which includes topoisomerase II inhibition, intercalation, and cell cycle impact. Olivacine—ellipticine’s isomer—shows similar properties. The objectives of this work were as follows: (a) to find a new path of olivacine synthesis, (b) to study the cytotoxic properties of olivacine and ellipticine in comparison to doxorubicin as well as their impact on the cell cycle, and (c) to investigate the cellular pharmacokinetics of the tested compounds to understand drug resistance in cancer cells better. SRB and MTT assays were used to study the anticancer activity of olivacine and ellipticine in vitro. Both compounds showed a cytotoxic effect on various cell lines, most notably on the doxorubicin-resistant LoVo/DX model, with olivacine’s cytotoxicity approximately three times higher than doxorubicin. Olivacine proved to be less effective against cancer cells and less cytotoxic to normal cells than ellipticine. Olivacine proved to have fluorescent properties. Microscopic observation of cells treated with olivacine showed the difference in sensitivity depending on the cell line, with A549 cells visibly affected by a much lower concentration of olivacine than normal NHDF cells. An increased percentage of cells in G0/G1 was observed after treatment with olivacine and ellipticine, suggesting an impact on cell cycle progression, potentially via higher p53 protein expression, which blocks the transition from G0/G1 to the S phase. Ellipticine induced apoptosis at a concentration as low as 1 μM. It has been proved that the tested compounds (ellipticine and olivacine) undergo lysosomal exocytosis. Reducing exocytosis is possible through the use of compounds that inhibit the activity of the proton pump. Olivacine and ellipticine exhibited diverse cytotoxicity against a panel of cancer cells. Analysis of the lysosomal exocytosis of olivacine and ellipticine shows the need to look for derivatives with comparable anticancer activity but reduced weak base character.

Introduction High utilization of antimicrobial agent (AMA) and inappropriate usage in an intensive care unit (ICU) intensifies resistant organism, morbidity, mortality, and treatment cost. Prescription audit and active feedback are a proven method to check the irrational prescription. To analyze and compare the utilization of drugs, the World Health Organization (WHO) proposed daily defined dose (DDD)/100 patient days and days of therapy (DOT)/100 patient days to measure utilization of AMAs. Data of AMAs utilization are required for planning an antibiotic policy and for follow-up of intervention strategies. Materials and methods A prospective observational study was conducted for 1 year from July 2018 to June 2019 and the data obtained from ICU of a tertiary care hospital. The demographic data, the disease data, and the utilization of different classes of AMAs [WHO–Anatomical Therapeutic Chemical (ATC) classification] as well as their cost were recorded. Total number of patient days, DDD, DDD/100 patient days, and DOT/100 patient days were calculated as proposed by the WHO. Statistical analysis was performed using statistical software SPSS version 25.0. The descriptive analysis was performed using summary statistics median [interquartile range (IQR)]. Results A total 939 patients were included, out of them 332 (35.4%) were female. The median age of the total patients was 58 (45–70). The median length of stay in ICU was 3 days. Mortality rate during our study period was 38.6%. The highly utilized AMAs in our study was ceftriaxone (36.95 DDD/100 patient days) followed by piperacillin/tazobactam (31.57), meropenem (26.4), doxycycline (21.53), and polymyxin B (21.38). The association between APACHE II and SOFA score with use of restricted antibiotics found to be statistical significant (p value 0.018 and 0.000, respectively). The cost of antibiotics per patient and patient days were $449.97 and $93.77, respectively, while median value of total cost was $2,343.26. Conclusion Ceftriaxone was the highest utilized AMA. The risk of receiving restricted antibiotics intensified with increasing prevalence of multidrug resistance bacteria and associated comorbidities. High treatment cost is responsible for higher utilization of restricted antibiotics in ICU. How to cite this article Patra SK, Mishra SB, Rath A, Samal S, Iqbal SN. Study of Antimicrobial Utilization and Cost of Therapy in Medicine Intensive Care Unit of a Tertiary Care Hospital in Eastern India. Indian J Crit Care Med 2020;24(10):938–942.

Background To compare the efficacy and safety of double-carbapenem therapy (DCT) with other antibiotics for the treatment of multidrug resistant (MDR) Gram-negative bacterial infections. Methods Cochrane Library, PubMed, Embase and Web of Science as well as Chinese databases were searched from database establishment to February 2019. All types of studies were included if they had evaluated efficacy and safety of DCT regimens in patients with MDR Gram-negative bacterial infections. Clinical response, microbiological response, adverse events and mortality were the main outcomes. The protocol was registered with PROSPERO No. CRD42019129979. Results Three cohort or case-control studies consisting of 235 patients and 18 case series or case reports consisting of 90 patients were included. The clinical and microbiological responses were similar between DCT and other regimens in patients with carbapenem-resistant Enterobacteriaceae (CRE) infection. DCT achieved a lower mortality than comparators in patients with CRE infection (OR = 0.44, 95% CI = 0.24–0.82, P = 0.009). Ertapenem was the most reported antibiotic in DCT regimens in case series or case reports. Moreover, clinical and microbiological improvements were found in 59 (65.6%) and 63 (70%) in total 90 cases, respectively. Conclusions DCT was as effective as other antibiotics in treating MDR Gram-negative bacterial infections, with similar efficacy response and lower mortality. DCT could be an alternative therapeutic option in the treatment of MDR Gram-negative bacterial infections. High-quality randomized controlled trials were required to confirm the beneficial effects of DCT.

Background Treating severe infections due to multidrug-resistant Gram-negative bacteria (MDR-GNB) is one of the most important challenges for clinicians worldwide, partly because resistance may remain unrecognized until identification of the causative agent and/or antimicrobial susceptibility testing (AST). Recently, some novel rapid test for identification and/or AST of MDR-GNB from positive blood cultures or the blood of patients with bloodstream infections (BSIs) have become available. Objectives The objective of this narrative review is to discuss the advantages and limitations of different rapid tests for identification and/or AST of MDR-GNB from positive blood cultures or the blood of patients with BSI, as well as the available evidence on their possible role to improve therapeutic decisions and antimicrobial stewardship. Sources Inductive PubMed search for publications relevant to the topic. Content The present review is structured in the following way: (a) rapid tests on positive blood cultures; (b) rapid tests directly on whole blood; (c) therapeutic implications. Implications Novel molecular and phenotypic rapid tests for identification and AST show the potential for favourably influencing patients' outcomes and results of antimicrobial stewardship interventions by reducing both the time to effective treatment and the misuse of antibiotics, although the interpretation about their impact on actual therapeutic decisions and patients' outcomes is still complex. Factors such as feasibility and personnel availability, as well as the detailed knowledge of the local microbiological epidemiology, need to be considered very carefully when implementing novel rapid tests in laboratory workflows and algorithms. Providing high-level, comparable evidence on the clinical impact of rapid identification and AST is becoming of paramount importance for MDR-GNB infections, since in the near future rapid identification of specific resistance mechanisms could be crucial for guiding rapid, effective, and targeted therapy against specific resistance mechanisms.

Purpose: A retrospective study was first performed to assess the multidrug resistant (MDR) pathogen in severe acute pancreatitis (SAP) patients who were treated using the step-up approach. We aim to assess the risk factors between MDR pathogen and potential covariates in SAP patients. Methods: The clinical data of 51 SAP patients who were treated from June, 2013 to December, 2016 were retrospectively collected. A total of 23 patients in the MDR group and 28 patients in the non-MDR group were reviewed. The risk factors for MDR pathogen-induced infections in SAP patients were analyzed. Results: Hyperlipidemia was the leading cause of SAP in our study. The mean duration of hospital stay was significantly longer in the patients with MDR pathogen infections (P=0.0135). The hospitalization expenses of MDR group were much higher than those in non-MDR group. The mortality of MDR group (56.5%) was higher than that in non-MDR group (28.6%) (P=0.0436). Gram-negative isolates (63.8%) were commonly detected in SAP patients. Acinetobacter baumannii was the most common MDR pathogens. Systemic disease (P = 0.0136), initial use of carbapenem (P = 0.0438), and open necrosectomy (P = 0.0002) were the potential risk factors for MDR pathogen-induced infections in SAP. Furthermore, the logistic regression analysis revealed that open necrosectomy was the independent variable for MDR infections (OR: 15.6, 95% CI: 2.951–82.469, P = 0.0012). Conclusions: MDR pathogen-induced infections were common in SAP patients and Acinetobacter baumannii was the main pathogen. Meanwhile, open necrosectomy was the independent risk factor for the infection of MDR pathogen.

Santosh Kumar Yadav, 1, 2 Rajshree Bhujel, 2 Pradip Hamal, 3 Shyam Kumar Mishra, 2 Sangita Sharma, 2 Jeevan Bahadur Sherchand 2 1Department of Microbiology, Rajarshi Janak University, Janakpurdham, Nepal; 2Department of Clinical Microbiology, Institute of Medicine, Tribhuvan University Teaching Hospital, Kathmandu, Nepal; 3Department of Pathology, B.P. Koirala Memorial Cancer Hospital, Bharatpur, NepalCorrespondence: Santosh Kumar YadavDepartment of Microbiology, Rajarshi Janak University, Janakpurdham, NepalEmail santooshydv@gmail.comIntroduction: Acinetobacter baumannii has emerged as a significant multidrug-resistant (MDR) nosocomial pathogen worldwide and is responsible for various healthcare-associated infections. The MDR strains have been reported increasingly during the last decades in hospitalized patients. They have developed resistance to most of the available antibiotics and are known to produce various acquired β-lactamases. The β-lactamase producing strains have a potential for rapid dissemination in hospital settings, as it is often plasmid-mediated. The Infectious Diseases Society of America (ISDA) stated A. baumannii as one of the “red alert” pathogens that greatly threatens the utility of our current antibacterial armamentarium. The study attempted to investigate the spectrum and antimicrobial resistance among MDR A. baumannii and their potential implications in hospitalized patients in a tertiary care hospital of Nepal.Methods: This study was conducted at Tribhuvan University Teaching Hospital (TUTH), Nepal from January 2017 to December 2017. A total of 177 A. baumannii isolated fromhospitalized patients were included in the study. The AST was performed by disc diffusion method. The MDR strains were identified by the criteria of Magiorakos et al, ESBL production by CLSI guidelines, and AmpC β-lactamase production by the AmpC disc test. MBL and KPC production were detected as per the method of Tsakris et al.Results: Out of 177 A. baumannii, 91.0% were MDR isolates. Among the MDR isolates, the majority were isolated from respiratory tract specimens and were isolated from ICU patients. Most of the MDR isolates were resistant to all first-line antibiotics and all were completely sensitive to only polymyxin B and colistin sulfate. MBL (67.7%) was the common β-lactamase production among MDR isolates.Conclusion: Acinetobacter baumannii can cause a vast variety of infections in hospitalized patients. The highly resistant MDR strains are common in tertiary care hospitals. This bacteria lead to high morbidity and mortality as we are left with the only option of treating them by potentially toxic antibiotics like colistin sulfate and polymyxin B. Detection of drug resistance and rational use of antibiotics play a crucial role in the fight against this MDR pathogen.Keywords: Acinetobacter baumannii, hospitalized patients, multidrug resistant, metallo-β-lactamase

Objective To determine whether a single-use stethoscope diaphragm barrier surface remains aseptic when placed on pathogen-contaminated stethoscopes. Methods From May 31 to August 5, 2019, we tested 2 separate barriers using 3 different strains of 7 human pathogens, including extended-spectrum β-lactamase–producing Escherichia coli, methicillin-resistant Staphylococcus aureus, and vancomycin resistant Enterococcus faecium. Results For all diaphragms with either of the 2 barriers tested, no growth was recorded for any of the pathogens. Stethoscopes with aseptic barriers remained sterile for up to 24 hours. These single-use barriers also provided aseptic surfaces when stethoscope diaphragms were inoculated with human specimens, including saliva, stool, urine, and sputum. Conclusion Disposable aseptic diaphragm barriers may provide robust and efficient solutions to reduce transmission of pathogens via stethoscopes.

Objective: To estimate burden of multi drug resistant, extensively drug resistant and pan drug resistant superbugs isolated from various indoor microbiological specimen at tertiary care centers Rawalpindi. Study Design: Cross sectional study. Place and Duration of Study: Department of Microbiology in Institute of Pathology, from Jul 2017 to Jun 2018. Methodology: A total of 6126 bacteria isolated from various indoor microbiological specimen were included in the study. All specimen were collected aseptically and bacterial cultures were processed as per standard microbiological practices. Bacterial isolates were identified by using VITEK 2 systems-Version 08.01 (bio Merieux, France). Results: Out of 6126 bacteria isolated 76% were multi drug resistant, 44% were extensively drug resistant and 1.2% were pan drug resistant. About 83% and 3.8% and 0% of bacteria isolated from pus/tissue, 67%, 58%, 0.8% of bacteria recovered from urine, 72%, 52% and 4.5% of bacteria isolated from respiratory samples and 83%, 42% and 3.4%bacteria isolated from blood were multidrug resistant, extensively drug resistant and pan drug resistant respectively. Conclusion: The burden of MDR, extensively drug resistant and pan drug resistant among bacteria isolated from various indoor microbiological specimen is disturbingly high and highlights a serious public health problem. Coordinated efforts to implement new policies, renew research efforts and investment into new antimicrobials are needed to manage drug resistant crises.

Background: The purpose of this study was to assess the risk of venous thromboembolism (VTE) and the potential need for thromboprophylaxis in patients with tuberculosis (TB). Methods: A total of 103 patients who underwent treatment for TB at the King Khalid University Hospital in Riyadh between February 2015 to May 2018, the percentage of patients diagnosed with TB who developed VTE was assessed. This was a retrospective cohort study conducted at King Khalid University Hospital in Riyadh. Fisher's exact test was used to analyze the categorical variables.P < 0.05 was considered statistically significant. Results: Our data showed the prevalence of VTE in TB patients to be 2.93% (3/103). VTE occurred irrespective of the type of TB (pulmonary and/or extrapulmonary). All TB patients with VTE showed no significant association with factors such as human immunodeficiency virus coinfection, malignancy, and multidrug-resistant TB. Conclusion: Our study showed that TB patients in Saudi Arabia may be at a higher risk for developing VTE and should be carefully monitored as potential candidates for additional thromboprophylaxis; further studies are recommended to establish more reliable assessment and recommendations.

Background Studies that validate new antituberculous regimens take much more time to complete as mycobacteria tend to be cleared slowly with absence of valid biomarkers to monitor treatment and outcomes. Aim To assess whether erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level would evaluate the patient’s response toward antituberculosis medication. Patients and methods A prognostic cohort study was conducted on 25 newly diagnosed multidrug-resistant patients with positive smear admitted to Abbasia Chest Hospital. Sputum Ziehl–Neelsen, culture, and GeneXpert were done. CRP and ESR were tested monthly till sputum conversion while other active illnesses were excluded with each assessment to avoid false results. Results The mean age of patients was 34.80±12.33 years; 56% of them were men and 52% were smokers. All patients presented with cough, expectoration, and toxic manifestations; 44% presented with hemoptysis. All patients received ethionamide, cycloserine, and levofloxacin. Pyrazinamide was used in 96% of patients; amikacin and kanamycin were used in 52 and 44% of patients, respectively. Eighty-eight percent of patients showed sputum conversion (80% in the second month and further 8% in the third month of treatment. The reported mortality rate was 12%. ESR and CRP showed a significant decrease within the period of treatment (P=0.03 and 0.02, respectively), with a significant decrease after sputum conversion (P=0.02 and 0.03, respectively). Conclusion CRP and ESR showed equal capabilities of monitoring response to therapy in multidrug-resistant-tuberculosis. None of them was superior to the other in monitoring response to therapy.

Sait Egrilmez,1 Şeyda Yildirim-Theveny2 1Private Office, Izmir, Turkey; 2Adiyaman University, Training and Research Hospital, Adiyaman, TurkeyCorrespondence: Sait EgrilmezPrivate Office, 1593/1 Sok. No: 4 B Blok D: 41 Mansuroglu Mah, Bayrakli, Izmir 35535, TurkeyTel +90 505 4504765Email saitegrilmez@gmail.comAbstract: Bacterial keratitis is an important ophthalmic emergency and one of the most common causes of corneal blindness. The main causes of treatment resistance in bacterial keratitis are failure to eliminate predisposing factors, misdiagnosis and mistreatment. At first, exogenous, local and systemic predisposing factors that disturbing ocular surface must be eliminated to improve corneal ulcers and to prevent recurrences. Smears and scrapings for staining and culture are indispensable diagnostic tools for cases of sight-threatening keratitis (centrally located, multifocal, characterized by melting, painful). Main treatment agents in bacterial keratitis treatment are topical antibiotics. Until the results of culture antibiograms reach the ophthalmologist, empirical antibiotic selections based on direct microscopic examination and gram stain findings are the most appropriate initial treatment approach currently. S. aureus and coagulase-negative staphylococci (CoNS), the most common gram-positive agents, have resistance rates of more than 30% for fluoroquinolone and methicillin. Multidrug resistance rates are similarly high in these microorganisms. P. aeruginosa is the most common gram-negative micro-organism, in case of multidrug-resistant isolates, both functional and anatomical prognosis of the eyes are very poor. In cases of sight-threatening and resistant keratitis, antibiotic susceptibility testing containing imipenem, colistin, and linezolid is seeming to be an important requirement. Despite its efficiency limited to superficial cases, a nonpharmaceutical anti-infective treatment option such as corneal crosslinking for bacterial keratitis is an emerging hope, while antibiotic resistance increases.Keywords: bacterial keratitis, antibiotic resistance, multidrug resistant, corneal crosslinking

Abhijeet Singh, 1 Rajendra Prasad, 1, 2 Viswesvaran Balasubramanian, 1 Nikhil Gupta 3 1Department of Pulmonary Medicine, Vallabhbhai Patel Chest Institute, University of Delhi, New Delhi, Delhi 110007, India; 2Department of Pulmonary Medicine, King George Medical University, Lucknow, Uttar Pradesh 226003, India; 3Department of Internal Medicine, Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh 226010, IndiaCorrespondence: Rajendra PrasadDepartment of Pulmonary Medicine, Vallabhbhai Patel Chest Institute, University of Delhi, New Delhi, Delhi 110007, IndiaTel +91 9415 021 590Email rprasaddirvpci@gmail.comAbstract: Drug-resistant tuberculosis (DR-TB), including multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB), is considered a potential obstacle for elimination of TB globally. HIV coinfection with M/XDR-TB further complicates the scenario, and is a potential threat with challenging management. Reports have shown poor outcomes and alarmingly high mortality rates among people living with HIV (PLHIV) coinfected with M/XDR-TB. This coinfection is also responsible for all forms of M/XDR-TB epidemics or outbreaks. Better outcomes with reductions in mortality have been reported with concomitant treatment containing antiretroviral drugs for the HIV component and antitubercular drugs for the DR-TB component. Early and rapid diagnosis with genotypic tests, prompt treatment with appropriate regimens based on drug-susceptibility testing, preference for shorter regimens fortified with newer drugs, a patient-centric approach, and strong infection-control measures are all essential components in the management of M/XDR-TB in people living with HIV.Keywords: drug-resistant, HIV, multidrug-resistant, extensively drug-resistant, tuberculosis

Purpose: Graft- versus-host disease (GVHD) is an important complication after human leukocyte antigen (HLA) haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT), which may lead to poor prognosis. Our study intends to identify the efficacy and safety of mesenchymal stem cells (MSCs) for multidrug-resistant (MDR)-GVHD after HID HSCT. Methods: MDR-GVHD was referring to GVHD remaining no response to at least two types of therapy, and hUCB-MSCs were given at the dose of (1.0–2.0) × 106/kg once a week. Results: A total of 21 patients were enrolled in this retrospective study (acute GVHD (aGVHD): n = 14, chronic GVHD (cGVHD): n = 7). The median dose of MSCs was 1.2 × 106 cells/kg (range, 0.8–1.8 × 106) cells/kg, and the median numbers of infusion were 2 (range, 1–7) and 3 (range, 2–12) for MDR-aGVHD and MDR-cGVHD patients, respectively. In MDR-aGVHD patients, the overall response rate (ORR) was 57.1%, including 50.0% complete response (CR) and 7.1% partial response (PR), and the median time to response was 49.5 days (range, 16–118) days. The 2-year probability of overall survival after MSCs was 64.3%. Five patients (35.7%) developed infections after MSCs, and no obvious hematologic toxicities were observed. Five MDR-aGVHD patients died after MSCs treatments because of GVHD progression ( n = 1), severe infection (bacterial central nervous system infection: n = 1; fungal pneumonia: n = 2), and poor graft function ( n = 1). In MDR-cGVHD patients, three patients (42.9%) achieved PR after MSCs and the median time to response was 56 days (22–84) days. The ORRs for moderate and severe cGVHD were 50.0% and 33.3%, respectively. Four MDR-cGVHD patients died after MSCs treatments because of GVHD progression ( n = 2), severe fungal pneumonia ( n = 1), and relapse ( n = 1). Conclusion: MSCs treatment may be safe and effective for MDR-GVHD after HID HSCT.

Abrupt increase of multidrug-resistant, extensively drug-resistant, and pandrug-resistant bacteria may complicate the course, management, and costs of neurocritical patients and is associated with high morbidity and mortality rates. No data exists regarding risk factors for colonization by gram-negative pathogens in neurocritical patients. The aim of the study was to identify risk factors associated with colonization by multidrug-resistant, extensively drug-resistant, and pandrug-resistant gram-negative bacteria in neurocritical patients. We conducted a retrospective cohort study in a neurointensive care unit over a period of 3 years. We included adult neurocritical patients admitted for more than 48 h. We analyzed several factors including both anamnestic factors and admission diagnosis. Four hundred twenty neurocritical patients were retrospectively enrolled. Seventy-three patients developed colonization by multidrug-resistant and 53 by extensively drug-resistant gram negative pathogens. Logistic regression identified intensive care unit length of stay (LOS) as the strongest predictor for both multidrug-resistant (AUC 0.877; 95% CI 0.841–0.913) and extensively drug-resistant (AUC 0.839 0.787–0.892) gram negative pathogens. In addition, external ventricular drainage and intracerebral pressure monitoring catheter were risk factors for XDR. Survival analysis revealed that MDR bacteria colonization happens earlier (log-rank test p = 0.017). Optimization of healthcare strategies is required in order to reduce patients’ length of stay to prevent multi- and extensively-drug gram-negative colonizations. Indeed, an early external ventricular drainage and intracerebral pressure monitoring catheter removal is deemed necessary as soon as clinically appropriate.

Background: Tuberculosis (TB) is one of the most serious public health problems worldwide which is a chronic infectious disease and is still one of the major challenges for developing countries. This study was undertaken to identify Mycobacterium TB (MTB) in clinical specimens in hospitalized patients. Methods: The study was carried out on specimens from pulmonary and extrapulmonary suspected TB patients that were admitted to one of the largest tertiary hospitals located in Tehran, Iran from 2017 to 2021. The GeneXpert MTB/rifampin (RIF) method was applied to detect MTB and RIF resistance. Characteristics of demography, clinical features, and lifestyle were obtained from medical case records registered in the hospital. Results: Of 957 specimens, 92 (9.61%) were found positive for TB by GeneXpert assay. Of positive samples, 72 (78.26%) were considered pulmonary TB, and 20 (21.73%) of them are associated with extrapulmonary involvement. Four (4.3%) positive TB cases were categorized as rifampicin-resistant. Conclusion: This study showed a relatively high incidence rate of TB in distinct types of specimens in Iranian hospitalized patients but a low level of RIF resistance.

Cancer remains a major public health threat. The mitigation of the associated morbidity and mortality remains a major research focus. From a molecular biological perspective, cancer is defined as uncontrolled cell division and abnormal cell growth caused by various gene mutations. Therefore, there remains an urgent need to develop safe and effective antitumor drugs. The antitumor effect of plant extracts, which are characterized by relatively low toxicity and adverse effect, has attracted significant attention. For example, increasing attention has been paid to the antitumor effects of tetramethylpyrazine (TMP), the active component of the Chinese medicine Chuanqiong, which can affect tumor cell proliferation, apoptosis, invasion, metastasis, and angiogenesis, as well as reverse chemotherapeutic resistance in neoplasms, thereby triggering antitumor effects. Moreover, TMP can be used in combination with chemotherapeutic agents to enhance their effects and reduce the side effect associated with chemotherapy. Herein, we review the antitumor effects of TMP to provide a theoretical basis and foundation for the further exploration of its underlying antitumor mechanisms and promoting its clinical application.

Background and Objectives: Urinary tract infections (UTI) are the most common bacterial infections in both outpatient and inpatient department received for routine bacterial culture and sensitivity. We looked for significant bacteriuria in re- quested repeat urine sample after primary urine culture yielded significant growth (>105 CFU/ml) of ≥3 types of colonies. Also studied, different isolates grown with their sensitivity pattern and contamination rates of urine samples from different departments. Materials and Methods: In routine, primary urine cultures yielding ≥3 types of colonies on Cystine Lactose Electrolyte Deficient (C.L.E.D) were requested for repeat samples, collected with aseptic precautions after proper instructions. Data was analyzed for the Microbiological profile and its clinical correlation. Results: Among 617 received requested urine samples, 292 (47.3%) yielded significant bacteriuria. Clinical details were available for 252 cases out of which 100 (39.7%) showed asymptomatic bacteriuria, 87 (34.5%) complicated UTI and 65 (25.7%) uncomplicated UTI. Null hypothesis was rejected as 292 (47.3%) of the received repeat samples showed significant bacteriuria and 325 (53%) showed normal flora/no growth i.e. there is a 50% chance of getting either a positive culture or normal flora/no growth in repeat urine samples after the primary urine culture showed ≥3 types of colonies. It indicates the importance of requesting repeat urine samples for an accurate urine culture report. Male patients were significantly associ- ated with significant bacteriuria and complicated UTI (p= 0.001). Escherichia coli (n=112, 28%) was the most common fol- lowed by Klebsiella species (n=66, 16.4%) and Enterococcus species (n=69, 17.2%). 183 (45.6%) isolates were Multi-Drug Resistant (MDR) Gram Negative Bacilli (GNBs), Escherichia coli (50.3%) being most common. Vancomycin Resistant Enterococcus (VRE) (n=8, 2.0%) was also isolated. Conclusion: Our study justifies the rationale for asking a repeat urine samples which helps in providing an appropriate mi- crobiological report with antibiotic sensitivity pattern, hence preventing unwanted reporting of commensals/contaminants facilitating evidence based therapy.

Background & objectives: Since the bacterium, Acinetobacter baumannii (AB) has acquired resistance to almost all commercially available antibiotics, the search for alternative treatment options continues to be need of the hour. Bacteriophage therapy seems to be the most promising amongst various proposed alternatives (e.g. antimicrobial peptides, bacteriocin, probiotics, etc.). The present study, therefore, aimed to evaluate the effect of different dosages of specific phages in immunocompromised rodents in a septicaemia model caused by AB mimicking real clinical situations. Methods: The three most active and unique phages (ɸAb4, ɸAb7 and ɸAb14) were selected for this study. A constant dose (100 µl of 108 pfu/ml) of AB was given in all the experiments. Five different sets of experiments were designed: prophylactic administration of phage cocktail in the volume of 100 µl (109 pfu/ml) before and simultaneous with the bacterial challenge; and therapeutic i.e. administration of phage cocktail six, 12 and 24 h after bacterial challenge. Since there were deaths in mice when phage was given 24 h after bacterial challenge, the reduced dosage i.e. 100 µl of 107, 106, 105 pfu/ml of phage cocktail was also evaluated. Results: The administration of 100 µl (109 pfu/ml) of phage cocktail after six, 12 and 24 h of the bacterial challenge resulted in the mortality ranging between 20 to 60 per cent. However, no mortality could be observed with simultaneous or prophylactic administration of phages with the bacterial challenge. No mortality was observed with reduced doses of the cocktail (106 and105 pfu/ml). Interpretation & conclusions: As per the results of this study, it may be concluded that even if patients with acute infections report late to the hospital, a relatively low dose of the phage cocktail may be therapeutically beneficial.

ΔΕΝ ΔΙΑΤΙΘΕΤΑΙ ΠΕΡΙΛΗΨΗ, Livestock is an important reservoir of Shiga toxin-producing Escherichia coli and enterohemorrhagic E. coli (STEC/EHEC) strains and acts as a significant source of transmission to humans. In addition to the virulence of STEC/EHEC isolates, antibiotic resistance is also an escalating problem in these bacteria and increases the risk to public health. Therefore, the present study aimed to explore E. coli O157:H7 serotype and STEC/EHEC virulence genes in AmpC- and extended-spectrum beta-lactamase (ESBL)-producing E. coli isolates from cattle, chicken and sheep. A total of 61 confirmed AmpC- or ESBL-producing E. coli isolates were screened for the virulence genes (stx1, stx2, eae, ehxA, espP, katP and saa) and E. coli O157 (rfbO157) and H7 (fliCH7) genes by polymerase chain reaction (PCR). None of the ESBL-producing E. coli was positive for these genes, but six multidrug-resistant AmpC-producing E. coli were positive for the fliCH7 gene only. When considering the function of the H7 flagellar antigen of E. coli, it may be concluded that the development of ESBL/AmpC beta-lactamase production in the E. coli isolates with H7 flagella, which reside in the chicken intestine, may be potentially important for public health regarding both virulence and antimicrobial resistance.

The present study evaluates poly (butyl cyanoacrylate) nanoparticles (PBCA-NPs), double-coated with Tween 80 and polyethylene glycol (PEG) 20,000 as a potential carrier system for overcoming P-glycoprotein (P-gp) and breast cancer resistant protein (BCRP)-mediated multidrug resistance (MDR) in cancer cell lines. Doxorubicin-loaded PBCA-NPs were prepared by the anionic polymerization method and were successively double-coated with Tween 80 and PEG 20000 at varied concentrations. MDR reversing potential was investigated by cellular uptake in P-gp overexpressing cell line. And, the outcomes were verified by modified MTT assay in P-gp or BCRP overexpressing cell lines. The findings from the cell uptake study indicate that double-coated PBCA-NPs significantly enhanced doxorubicin accumulation within the cells. MTT assays revealed that double-coated PBCA-NPs significantly potentiated the sensitivity of doxorubicin in P-gp overexpressing cells, in comparison to free doxorubicin, single-, and un-coated PBCA-NPs, respectively. Moreover, further increase in concentration with Tween 80, double-coated PBCA-NPs significantly enhanced the sensitivity of doxorubicin in BCRP overexpressing cell line, in comparison to single- and double-coated formulations (with lower concentration of Tween 80). Hence, it could be concluded that double-coated PBCA-NPs can be used as a potential carrier for enhancing doxorubicin accumulation in MDR cancer cells.

Tuberculosis (TB), is one of the top 10 causes of death worldwide (WHO). According to the last Global TB report from the World Health Organization, 10 million persons were estimated to have had TB in 2019 worldwide, causing about 1.6 million deaths. Tuberculosis has not only a dramatic impact on the quality of life for the patients, but also has raised many socio-economic issues at a community level, especially in medium and high burden regions, such as India, China, and Indonesia. In 2014, WHO adopted the "End TB strategy" which aimed to reduce TB deaths by 90% between 2015 and 2030, to prevent new cases by 80% during the same period and to decrease the socioeconomic impact of the disease at a family level. Even though tuberculosis global incidence has decreased significantly, efforts still need to be made to reach these goals. Non-tuberculous mycobacteria (NTM), in contrast to Mycobacterium tuberculosis, are bacteria widely spread in the environment and can be found in a broad range of ecosystems such as soils and water, including drinking water systems. NTM are opportunistic pathogens associated with both pulmonary and extrapulmonary infections. This Research Topic collected articles addressing: (i) TB and NTMs associated diseases, diagnostic, control, and public health, (ii) mycobacterial genomics, (iii) and antimycobacterial drugs and resistance

Ceftolozane-tazobactam is currently the most active antipseudomonal agent, including multidrug-resistant extensively drug-resistant strains. Tazobactam provides additional activity against many extended-spectrum beta-lactamases Enterobacterales. Ceftolozane-tazobactam is formally approved for complicated urinary tract infection, complicated intra-abdominal infection, and hospital-acquired and ventilator-associated bacterial pneumonia. The clinical and microbiological success is over 70-80% in many series. However, resistant mutants to ceftolozane-tazobactam have been already described. Combination therapies with colistin or meropenem could be among the strategies to avoid the resistance emergence.

Yunying Wang,1 Hui Liu,2 Lijun Zhang,1 Bin Sun1 1Department of Laboratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Blood Transfusion, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Bin SunDepartment of Laboratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, No. 74 Linjiang Road, Yuzhong District, Chongqing, People’s Republic of ChinaTel +86 23-62887812Fax +86 23-63703244Email sunbin@cqmu.edu.cnPurpose: Infection and transmission of carbapenem-resistant Aeromonas is a serious threat to public health. Rapid and accurate detection carbapenem-resistant of these organisms is essential for reasonable treatment and infection control. This study aimed to find a simple and effective method to detect carbapenem-resistant phenotype in Aeromonas.Methods: A total of 131 clinical preserved Aeromonas strains were used in this study. The carbapenemase genes were detected by PCR. Modified carbapenem inactivation method (mCIM) in conjunction with EDTA-modified carbapenem inactivation method (eCIM) and simplified carbapenem inactivation method (sCIM) were performed to detect carbapenemases. We also designed a simple method, carbapenem inactivation method using supernatant (CIM-s), to detect the carbapenemase activity in the medium.Results: Of the 131 Aeromonas strains, 79 contained carbapenemase genes, including 68 blaCphA, 6 blaKPC-2, 2 blaNDM-1 and 3 blaKPC-2+CphA. However, routine antibiotic susceptibility testing could not completely identify carbapenemase-producing Aeromonas. In phenotypic assays, the sensitivity and specificity of mCIM were 100%. The combined mCIM and eCIM could distinguish serine carbapenemase and metallo-β-carbapenemases except co-producing organisms. The sensitivity and specificity of sCIM were 92.4% and 100%, respectively, which could not detect CphA totally. CIM-s results indicate that these carbapenemases could secrete into the medium to perform their hydrolytic activities and had a sensitivity and specificity of 97.5% and 100%, respectively.Conclusion: The combination of mCIM and eCIM can effectively detect and distinguish different types of carbapenemase in Aeromonas, and could be used as an important supplement approach to the antibiotic susceptibility testing.Keywords: Aeromonas, modified carbapenem inactivation method, carbapenemase, multidrug resistant, phenotypic detection

Escherichia coli has become one of the most important causes of calf diarrhea. The aim of this study is to determine the patterns of antimicrobial resistance of E. coli isolates from six cattle farms and to identify prominent resistance genes and virulence genes among the strains isolated from the diarrhea of calves. Antimicrobial susceptibility tests were performed using the disk diffusion method, and PCR was used to detect resistance and virulence genes. The prevalence of multidrug resistant (MDR) E. coli was 77.8% in dairy cattle and 63.6% in beef cattle. There were high resistance rates to penicillin (100%, 100%) and ampicillin (96.3%, 86.4%) in E. coli from dairy cattle and beef cattle. Interestingly, resistance rate to antimicrobials and distribution of resistance genes in E. coli isolated from dairy cattle were higher than those in beef cattle. Further analysis showed that the most prevalent resistance genes were blaTEM and aadA1 in dairy cattle and beef cattle, respectively. Moreover, seven diarrheagenic virulence genes (irp2, fyuA, Stx1, eaeA, F41, K99 and STa) were present in the isolates from dairy cattle, with a prevalence ranging from 3.7% to 22.22%. Six diarrheagenic virulence genes (irp2, fyuA, Stx1, eaeA, hylA and F41) were identified in the isolates from beef cattle, with a prevalence ranging from 2.27% to 63.64%. Our results provide important evidence for better exploring their interaction mechanism. Further studies are also needed to understand the origin and transmission route of E. coli in cattle to reduce its prevalence.

Amikacin and kanamycin are second-line injectables used in the treatment of multidrug-resistant tuberculosis (MDR-TB) based on the clinical utility of streptomycin, another aminoglycoside and first-line anti-TB drug. While streptomycin was tested as a single agent in the first controlled TB clinical trial, introduction of amikacin and kanamycin into MDR-TB regimens was not preceded by randomized controlled trials. A recent large retrospective meta-analysis revealed that compared with regimens without any injectable drug, amikacin provided modest benefits, and kanamycin was associated with worse outcomes. Although their long-term use can cause irreversible ototoxicity, they remain part of MDR-TB regimens because they have a role in preventing emergence of resistance to other drugs. To quantify the contribution of amikacin and kanamycin to second-line regimens, we applied two-dimensional matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging in large lung lesions, quantified drug exposure in lung and in lesions of rabbits with active TB, and measured the concentrations required to kill or inhibit growth of the resident bacterial populations. Using these metrics, we applied site-of-action pharmacokinetic and pharmacodynamic (PK-PD) concepts and simulated drug coverage in patients’ lung lesions. The results provide a pharmacological explanation for the limited clinical utility of both agents and reveal better PK-PD lesion coverage for amikacin than kanamycin, consistent with retrospective data of contribution to treatment success. Together with recent mechanistic studies dissecting antibacterial activity from aminoglycoside ototoxicity, the limited but rapid penetration of streptomycin, amikacin, and kanamycin to the sites of TB disease supports the development of analogs with improved efficacy and tolerability.

For decades, the spread of multidrug-resistant (MDR) Acinetobacter baumannii has been rampant in critically ill, hospitalized patients. Traditional antibiotic therapies against this pathogen have been failing, leading to rising concerns over management options for patients. Two new antibiotics, eravacycline and omadacycline, were introduced to the market and have shown promising results in the treatment of Gram-negative infections. Since these drugs are newly available, there is limited in vitro data about their effectiveness against MDR A. baumannii or even susceptible strains. Here, we examined the effectiveness of 22 standard-of-care antibiotics, eravacycline, and omadacycline against susceptible and extensively drug-resistant (XDR) A. baumannii patient isolates from Cooper University Hospital. Furthermore, we examined selected combinations of eravacycline or omadacycline with other antibiotics against an XDR strain. We demonstrated that this collection of strains is largely resistant to monotherapies of carbapenems, fluoroquinolones, folate pathway antagonists, cephalosporins, and most tetracyclines. While clinical breakpoint data are not available for eravacycline or omadacycline, based on minimum inhibitory concentrations, eravacycline was highly effective against these strains. The aminoglycoside amikacin alone and in combination with eravacycline or omadacycline yielded the most promising results. Our comprehensive characterization offers direction in the treatment of this deadly infection in hospitalized patients.

Extended-spectrum β-lactamases producing Escherichia coli (ESBL-EC) lend resistance to most β-lactam antibiotics. Because of limited treatment options, ESBL-EC infections are generally more difficult to treat, leading to higher hospital costs, reduced rates of microbiological and clinical responses, and a threat to the patient’s life. This study aimed to determine the antibiotic resistance pattern of ESBL-EC isolated from patients with urinary tract infection in Morocco. This retrospective laboratory-based study was conducted at Cheikh Khalifa International University Hospital, Casablanca, from January 2016 to June 2019. A total of 670 urine samples were collected from urinary tract infection patients and processed by standard microbiological methods. In vitro susceptibility testing to different antibiotics of all identified isolates of Escherichia coli (E. coli) was performed following Kirby–Bauer’s disc diffusion method on Mueller–Hinton Agar according to the EUCAST standards. The reviewing of ESBL-EC was confirmed by the appearance of a characteristically shaped zone referred to as a “champagne cork” using the Combined Disk Test. Among a total of 438 E. coli isolated from nonrepetitive urine samples, two hundred fifty-nine (59%) were ESBL-EC, of which 200 (77%) were isolated from adult patients (over the age of 50) and the majority were female. All ESBL-EC isolates were resistant to third-generation cephalosporin and quinolones and sensitive to carbapenem and fosfomycin. Knowledge of antimicrobial resistance patterns in ESBL-EC, the major pathogen associated with urinary tract infection, is indispensable as a guide in choosing empirical antimicrobial treatment.

The treatment of invasive Escherichia coli infections is a challenge because of the emergence and rapid spread of multidrug resistant strains. Particular problems are those strains that produce extended spectrum β-lactamases (ESBL’s). Although the global characterization of these enzymes is advanced, knowledge of their molecular basis among clinical E. coli isolates in Ethiopia is extremely limited. This study intends to address this knowledge gap. The study combines antimicrobial resistance profiling and molecular epidemiology of ESBL genes among 204 E. coli clinical isolates collected from patient urine, blood, and pus at four geographically distinct health facilities in Ethiopia. All isolates exhibited multidrug resistance, with extensive resistance to ampicillin and first to fourth line generation cephalosporins and sulfamethoxazole-trimethoprim and ciprofloxacin. Extended spectrum β-lactamase genes were detected in 189 strains, and all but one were positive for CTX-Ms β-lactamases. Genes encoding for the group-1 CTX-Ms enzymes were most prolific, and CTX-M-15 was the most common ESBL identified. Group-9 CTX-Ms including CTX-M-14 and CTX-27 were detected only in 12 isolates and SHV ESBL types were identified in just 8 isolates. Bacterial typing revealed a high amount of strains associated with the B2 phylogenetic group. Crucially, the international high risk clones ST131 and ST410 were among the sequence types identified. This first time study revealed a high prevalence of CTX-M type ESBL’s circulating among E. coli clinical isolates in Ethiopia. Critically, they are associated with multidrug resistance phenotypes and high-risk clones first characterized in other parts of the world.