Diarrheal Diseases: A Review on Gastroenteritis Bacteria Global Burden and Alternative Control of Multidrug-Resistant Strains

Diarrheal diseases represent a significant and pervasive health challenge for humanity. The aetiology of diarrheal diseases is typically associated with the presence of enteropathogens, including viruses, bacteria and parasites. The implementation of preventive measures, including the maintenance of good food hygiene, effective water sanitation, and the development of rotavirus vaccines, has resulted in a notable reduction in the prevalence of the disease. However, the emergence of bacterial multidrug resistance due to the past or present inappropriate use of antibiotics has rendered bacterial infections a significant challenge. The objective of this review is threefold: firstly, to provide an overview of diarrheal diseases associated with bacteria;secondly, to offer a concise analysis of bacterial multidrug resistance on a global scale;and thirdly, to present the potential of filamentous fungi as an alternative solution to the challenge posed by multidrug-resistant strains. Campylobacter spp. is the most dangerous bacteria, followed by Shigella spp. and Vibrio cholerae in all age groups combined. However, Shigella spp. was the deadliest in children under five years of age and, together with E. coli, are the most antibiotic-resistant bacteria. With their highly developed secondary metabolism, fungi are a reservoir of natural bioactive compounds.

Ventilator-associated pneumonia in patients with cancer: Impact of multidrug resistant bacteria

BACKGROUND Patients with cancer have several risk factors for developing respiratory failure requiring mechanical ventilation(MV).The emergence of multidrug resistant bacteria(MDRB)has become a public health problem,creating a new burden on medical care in hospitals,particularly for patients admitted to the intensive care unit(ICU).AIM To describe risk factors for ventilator-acquired pneumonia(VAP)in patients with cancer and to evaluate the impact of MDRB.METHODS A retrospective study was performed from January 2016 to December 2018 at a cancer referral center in Mexico City,which included all patients who were admitted to the ICU and required MV≥48 h.They were classified as those who developed VAP versus those who did not;pathogens isolated,including MDRB.Clinical evolution at 60-d was assessed.Descriptive analysis was carried out;comparison was performed between VAP vs non-VAP and MDRB vs non-MDRB.RESULTS Two hundred sixty-three patients were included in the study;mean age was 51.9 years;52.1%were male;68.4%had solid tumors.There were 32 episodes of VAP with a rate of 12.2%;11.5 episodes/1000 ventilation-days.The most frequent bacteria isolated were the following:Klebsiella spp.[n=9,four were Extended-Spectrum Beta-Lactamase(ESBL)producers,one was Carbapenem-resistant(CR)];Escherichia coli(n=5,one was ESBL),and Pseudomonas aeruginosa(n=8,two were CR).One Methicillin-susceptible Staphylococcus aureus was identified.In multivariate analysis,the sole risk factor associated for VAP was length of ICU stay(OR=1.1;95%CI:1.03-1.17;P=0.003).Sixty-day mortality was 53%in VAP and 43%without VAP(P=0.342).There was not higher mortality in those patients with MDRB.CONCLUSION This study highlights the high percentage of Gram-negative bacteria,which allows the initiation of empiric antibiotic coverage for these pathogens.In this retrospective,single center,observational study,MDRB VAP was not directly linked to increased mortality at 60 days.

Antibacterial activities of ethanol extracts of Philippine medicinal plants against multidrug-resistant bacteria

Objective: To investigate the antibacterial activities of crude ethanol extracts of 12 Philippine medicinal plants.Methods: Crude ethanol extracts from 12 Philippine medicinal plants were evaluated for their antibacterial activity against methicillin-resistant Staphylococcus aureus, vancomycinresistant Enterococcus, extended spectrum β-lactamase-producing, carbapenem-resistant Enterobacteriaceae and metallo-β-lactamase-producing Pseudomonas aeruginosa and Acinetobacter baumannii. Results: The leaf extracts of Psidium guajava, Phyllanthus niruri, Ehretia microphylla and Piper betle(P. betle) showed antibacterial activity against the Gram-positive methicillinresistant Staphylococcus aureus and vancomycin-resistant Enterococcus. P. betle showed the highest antibacterial activity for these bacteria in the disk diffusion(16-33 mm inhibition diameter), minimum inhibitory concentration(19-156 μg/m L) and minimum bactericidal concentration(312 μg/m L) assays. P. betle leaf extracts only showed remarkable antibacterial activity for all the Gram-negative multidrug-resistant bacteria(extended spectrum β-lactamaseproducing, carbapenem-resistant Enterobacteriaceae and metallo-β-lactamase-producing) in the disk diffusion(17-21 mm inhibition diameter), minimum inhibitory concentration(312-625 μg/m L) and minimum bactericidal concentration(312-625 μg/m L) assays. Conclusions: P. betle had the greatest potential value against both Gram-negative and Grampositive multidrug-resistant bacteria. Favorable antagonistic activities were also exhibited by the ethanol extracts of Psidium guajava, Phyllanthus niruri and Ehretia microphylla.

Extensively drug-resistant bacteria are an independent predictive factor of mortality in 130 patients with spontaneous bacterial peritonitis or spontaneous bacteremia

AIM: To evaluate the epidemiology and outcomes of culture-positive spontaneous bacterial peritonitis (SBP) and spontaneous bacteremia (SB) in decompensated cirrhosis.METHODS: We prospectively collected clinical, laboratory characteristics, type of administered antibiotic, susceptibility and resistance of bacteria to antibiotics in one hundred thirty cases (68.5% males) with positive ascitic fluid and/or blood cultures during the period from January 1, 2012 to May 30, 2014. All patients with SBP had polymorphonuclear cell count in ascitic fluid > 250/mm3. In patients with SB a thorough study did not reveal any other cause of bacteremia. The patients were followed-up for a 30-d period following diagnosis of the infection. The final outcome of the patients was recorded in the end of follow-up and comparison among 3 groups of patients according to the pattern of drug resistance was performed.RESULTS: Gram-positive-cocci (GPC) were found in half of the cases. The most prevalent organisms in a descending order were Escherichia coli (33), Enterococcus spp (30), Streptococcus spp (25), Klebsiella pneumonia (16), S. aureus (8), Pseudomanas aeruginosa (5), other Gram-negative-bacteria (GNB) (11) and anaerobes (2). Overall, 20.8% of isolates were multidrug-resistant (MDR) and 10% extensively drug-resistant (XDR). Health-care-associated (HCA) and/or nosocomial infections were present in 100% of MDR/XDR and in 65.5% of non-DR cases. Meropenem was the empirically prescribed antibiotic in HCA/nosocomial infections showing a drug-resistance rate of 30.7% while third generation cephalosporins of 43.8%. Meropenem was ineffective on both XDR bacteria and Enterococcus faecium (E. faecium). All but one XDR were susceptible to colistin while all GPC (including E. faecium) and the 86% of GNB to tigecycline. Overall 30-d mortality was 37.7% (69.2% for XDR and 34.2% for the rest of the patients) (log rank, P = 0.015). In multivariate analysis, factors adversely affecting outcome included XDR infection (HR = 2.263, 95%CI: 1.005-5.095, P = 0.049), creatinine (HR = 1.125, 95%CI: 1.024-1.236, P = 0.015) and INR (HR =1.553, 95%CI: 1.106-2.180, P = 0.011).CONCLUSION: XDR bacteria are an independent life-threatening factor in SBP/SB. Strategies aiming at restricting antibiotic overuse and rapid identification of the responsible bacteria could help improve survival.

Isolation and Identification of Multi-Drug Resistant Strains of Non-Lactose Fermenting Bacteria from Clinical Refuses in Major Hospitals of Khyber Pakhtunkhwa, Pakistan

Purpose: The present studied was performed in order to investigate the drug resistance of different non-lactose fermenting gram negative bacteria from clinical isolates. The bacteria were morphologically characterized through culturing and gram staining techniques were used for the identification of different bacterial strains. Methods: A total of 324 samples were collected from patients, after they were diagnosed by physicians at different hospitals at district Peshawar. Samples were morphologically identified by blood agar, MacConkey agar and Eosine Methylene Blue, identified by gram staining techniques. Modified Kirby-Bauer Disc diffusion method was used to test the in-vitro susceptibility of the identified isolates to different antibiotics. Results: The non-lactose fermenting gram negative bacteria were isolated from samples of blood (33.30%), pus/ wound (33.30%), urine (23.30%) and from ascetic/pleural fluids (10.20%). The study revealed that Pseudomonas aeroginosa showed high resistance against Gentamicin (74%) and Aztreonam (74%), followed by Ciprofloxacin (59.20%) and Amikacin (33.30). Tazocin was active as low resistance (18.50%) is shown. More resistance was seen in Morganella morganii against Aztreonam (77.7%) followed by Gentamicin (62.90%), Ciprofloxacin (40.70%). Tazocin show low resistance (3.70%). Multidrug resistant Proteus mirabillis was highly resistance to Gentamicin (66.60%), followed by Aztreonam (62.90%), Amikacin (55.50%), Ciprofloxacin (40.20%) and low resistance to Tazocin was (22.20%). Salmonella typhi demonstrated high resistance against Amikacin (62.90%), followed by Aztreonam (48.10%), Tazocin (40.70%). Gentamicin showed low resistance (29.60%), and hence it is more active against S. typhi. Conclusions: It can be concluded from the present study that different species of non-lactose fermenting gram negative bacteria have shown a different resistivity pattern. This study is a gate way for better and suitable management strategy for the infections caused by non-Lactose fermenting bacteria in the sampling region.

Synergistic Effect of Combined Antibiotics against Some Selected Multidrug Resistant Human Pathogenic Bacteria Isolated from Poultry Droppings in Akure, Nigeria

Antibiotic resistant bacteria pass between humans, between animals and between humans and animals in both directions, the use of antibiotics in poultry has contributed to multiple antibiotic resistant in pathogenic bacteria and use of two antibiotics might prevent the emergence of resistance to either. In this study, synergistic effect of combined antibiotics against multidrug resistant human pathogenic bacterial isolates from poultry droppings in Akure, Nigeria was examined. Collection of samples, isolation and identification of bacteria were carried out using standard microbiological method, antibiotic sensitivity test was performed by disc diffusion method and zone of inhibition was used to interpret the sensitivity test as resistant, susceptible or intermediate while combined effects of two antibiotics were investigated by macrobroth dilution and checkerboard assay methods while the synergetic effects of combined antibiotics were calculated using Fractional Inhibitory Concentration (FIC) and percentage synergistic interaction was calculated. All the ten (10) species of bacterial isolates were multidrug resistant and are less resistant to ofloxacin. The highest percentage synergistic interactions observed were Ofloxacin + Amoxicillin (90%), Ciprofloxacin + Amoxicillin (90%), Tetracycline + Amoxicillin (70%), Tetracycline + Augmentin (80%), Cotrimoxazol + Amoxicillin (50%), Cotrimoxazol + Augmentin (70%), Chloramphenicol + Amoxicillin (70%) and Chloramphenicol + Augmentin (80%). Poultry droppings is a potential source of human pathogenic bacteria, high frequency of multiple antibiotic resistance bacteria observed in this study is of great treat to man as this may cause the treatment of infection caused by these bacteria to be difficult. Combination of beta-lactam antibiotic with fluoroqunolones, tetracycline, Chloramphenicol and Cotrimoxazole was synergetic and this will reduce dose related toxicity and prevent resistance to single antibiotic.

Isolation and Identification of Multi-Drug Resistant Strains of Non-Lactose Fermenting Bacteria from Clinical Isolates

Purpose: We studied the drug resistance of different microbes from clinical isolates. The morphological characteristics of bacteria were observed through culture characteristics and by carrying out gram staining techniques while the biochemical characteristics of bacteria were carried out by biochemical test. Methods: A total of 324 samples were collected from suspected patients visiting different hospitals at district Peshawar. For morphological identification, samples of clinical isolates were analyzed by blood agar, MacConkey agar and Eosine Methylene Blue, identified by gram staining and characterized by different biochemical tests. Antibiotic Sensitivity test by Modified Kirby-Bauer Disc diffusion method was used to test the in-vitro susceptibility of the identified isolates to different antibiotics such as Ceftazidime, Ceftazidime, Ceftriaxone, Cefepime and Imipenem. Results: These resistant non-lactose fermenting gram negative bacteria were isolated from samples of pus/wound (33.30%, n = 108/324), blood (33.30%, n = 108/324), urine (23.30%, n = 75/324) and from ascetic/pleural fluids (10.20%, n = 33/324). The study revealed that the percentage of non-fermenting bacterial infection was higher in females (53%) as compared to males (47%) along with higher infection observed in the age group of 11 - 30 years. Pseudomonas aeroginosa showed high resistance against Cefepime (88.80%), followed by Cefoperazone (55.50%), Ceftazidime (48.10%), Ceftriaxone (33.30%). Imipenem was active with low resistance (7.40%). More resistance was seen in Morganella morganii against Imipenem (66.70%) followed by Cefoperazone (55.50%), Ceftriaxone (55.50%). Cefepime showed low resistance (11%). Multi-drug resistant Proteus mirabillis was highly resistance to Ceftriaxone (74.07%), followed by Cefepime (59.20%), Cefoperazone (44.40%) and low resistance for Imipenem (25.90%). Salmonella typhi demonstrated high resistance against Imipenem (74.07%), followed by Ceftriaxone (40.70%), Ceftazidime (37.03%). Cefepime showed low resistance (3.70%), hence it is more active against S. typhi. Conclusions: The different species of non-lactose fermenting gram negative bacteria have shown a different resistivity pattern in the present study. Therefore identification of non-lactose fermenting gram negative bacteria and looking after their resistivity/susceptibility pattern are important for suitable management of the infections caused by them.

Isolation and Characterization of Multi-Drug Resistant Bacteria from Hospital Wastewater Sites around the City of Aizawl, Mizoram

A microbial study was conducted from wastewater soils of hospitals in Aizawl, Mizoram, India which were in existence for a longtime. The isolated bacteria from the wastewater soils were found to be mainly of Morganella morganii and Bacillus cereus and these isolated bacteria were found to be very resistant to a wide range of antibiotics and heavy metals. Antibiotics that were used for treating infections caused by these bacteria like chloramphenicol and ciprofloxacin were also found to be insensitive. The degree of resistance was also very high when compared to earlier reports of antibiotic resistance observed in the corresponding bacteria. Our results suggested that the high degree of resistance is probably conferred by the continued exposure to antibiotics from hospital waste leading to a selected population of highly antibiotics-resistant bacteria.

Control of multidrug-resistant planktonic Acinetobacter baumannii:biocidal efficacy study by atmospheric-pressure air plasma

In this research,an atmospheric-pressure air plasma is used to inactivate the multidrug-resistant Acinetobacter baumannii in liquid.The efficacy of the air plasma on bacterial deactivation and the cytobiological variations after the plasma treatment are investigated.According to colony forming units,nearly all the bacteria（6-log） are inactivated after 10 min of air plasma treatment.However,7% of the bacteria enter a viable but non-culturable state detected by the resazurin based assay during the same period of plasma exposure.Meanwhile,86% of the bacteria lose their membrane integrity in the light of SYTO 9/PI staining assay.The morphological changes in the cells are examined by scanning electron microscopy and bacteria with morphological changes are rare after plasma exposure in the liquid.The concentrations of the long-living RS,such as H2O2,NO3^- and O3,in liquid induced by plasma treatment are measured,and they increase with plasma treatment time.The changes of the intracellular ROS may be related to cell death,which may be attributed to oxidative stress and other damage effects induced by RS plasma generated in liquid.The rapid and effective bacteria inactivation may stem from the RS in the liquid generated by plasma and air plasmas may become a valuable therapy in the treatment of infected wounds.

耐药肺结核合并咽炎患者多重耐药α-溶血性链球菌分子流行病学调查及风险模型构建

目的探究耐药肺结核合并咽炎患者多重耐药α-溶血性链球菌分子流行病学调查并构建风险模型。方法选择2019年3月-2022年1月在我院接受治疗的耐药肺结核合并咽炎患者150例为研究对象。采用PhoenixTM-100全自动细菌检测分析系统进行药敏试验。依据脉冲场凝胶电泳(Pulsed field gel electrophoresis,PFGE)和多点位序列分析(Multilocus sequence type,MLST)技术对其中92例多重耐药草绿色链球菌(Viridans Group Streptococcus,VGS)感染患者进行分子流行病学调查。根据是否发生多重耐药感染将患者分为感染组(n=92)和非感染组(n=58),多因素Logistic分析多重耐药VGS感染的独立影响因素并构建简易评分模型划分感染风险等级并进行验证。结果药敏结果显示,VGS对亚胺培南、厄他培南的敏感性高,敏感率为100%;PFGE分型和MLST分型结果显示,92株多重耐药VGS菌株可分为5种PFGE克隆型和15种ST型;多因素Logistic分析结果表明,年龄、呕吐、腹泻、降钙素原、中性粒细胞、白细胞是导致耐药肺结核合并咽炎患者感染多重耐药VGS菌株的独立危险因素(P<0.05);年龄、白细胞、中性粒细胞和降钙素原与多重耐药VGS感染风险关联密切;简易评分模型结果显示其预测效能较好。结论年龄、降钙素原、中性粒细胞、白细胞是感染多重耐药VGS菌株关联最大的独立危险因素,为临床筛查和预防有多重耐药VGS感染风险的耐药肺结核合并咽炎患者提供了理论基础。

Nosocomial spontaneous bacterial peritonitis antibiotic treatment in the era of multi-drug resistance pathogens: A systematic review

To systematically review literature upon aetiology of nosocomial spontaneous bacterial peritonitis (N-SBP) given the rising importance of multidrug-resistant (MDR) bacteria. METHODSA literature search was performed on MEDLINE and Google Scholar databases from 2000 to 15th of November 2016, using the following search strategy: “spontaneous” AND “peritonitis”. RESULTSThe initial search through electronic databases retrieved 2556 records. After removing duplicates, 1958 records remained. One thousand seven hundred and thirty-five of them were excluded on the basis of the screening of titles and abstract, and the ensuing number of remaining articles was 223. Of these records, after careful evaluation, only 9 were included in the qualitative analysis. The overall proportion of MDR bacteria turned out to be from 22% to 73% of cases across the studies. CONCLUSIONN-SBP is caused, in a remarkable proportion, by MDR pathogens. This should prompt a careful re-assessment of guidelines addressing the treatment of this clinical entity.

Five-year analysis of isolated pathogens and antibiotic resistance of ocular infections from two large tertiary comprehensive hospitals in east China

AIM:To analyze the spectrum of isolated pathogens and antibiotic resistance for ocular infections within 5y at two tertiary hospitals in east China.METHODS:Ocular specimen data were collected from January 2019 to October 2023.The pathogen spectrum and positive culture rate for different infection location,such as keratitis,endophthalmitis,and periocular infections,along with antibiotic resistance were analyzed.RESULTS:We included 2727 specimens,including 827(30.33%)positive cultures.A total of 871 strains were isolated,530(60.85%)bacterial and 341(39.15%)fungal strains were isolated.Gram-positive cocci(GPC)were the most common ocular pathogens.The most common bacterial isolates were Staphylococcus epidermidis(25.03%),Staphylococcus aureus(7.46%),Streptococcus pneumoniae(4.59%),Corynebacterium macginleyi(3.44%),and Pseudomonas aeruginosa(3.33%).The most common fungal genera were Fusarium spp.(12.74%),Aspergillus spp.(6.54%),and Scedosporium spp.(5.74%).Staphylococcus epidermidis strains showed more than 50%resistance to fluoroquinolones.Streptococcus pneumoniae and Corynebacterium macginleyi showed more than 90%resistance to erythromycin.The percentage of bacteria showing multidrug resistance(MDR)significantly decreased(χ^(2)=17.44,P=0.002).CONCLUSION:GPC are the most common ocular pathogens.Corynebacterium macginleyi,as the fourth common bacterium,may currently be the local microbiological feature of east China.Fusarium spp.is the most common fungus.More than 50%of the GPC are resistant to fluoroquinolones,penicillins,and macrolides.However,the proportion of MDR strains has been reduced over time.

EXPRESSION OF MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN IN HUMAN GASTRIC AND RENAL CARCINOMAS

Objective The clinical signilicance of exPression of multidrug resistance- associated protein (MRP) in gastric and renal carcinoma was investigated. Methods LSAB immunohistochemistry was performed to detect eopression of MRP in the carcinoma tissues of 52 patients with gastric carcinoma and 20 cases with renal cell carcinoma. Results The positive expression rate of MRP was 38.5% (20/52) in gastric carcinoma tissues, and 60% (12/20) in renal carcinoma tissues. The expression of MRP both on cellular membrane and in cytoplasm was observed, but the expression in cytoplasm (thick granule) was more obvious. The positive expression rates of MRP in advanced gastric and renal carcinoma (Ⅲ orⅣ stage) were 60% (15/25) and 88.90% (8/9) reSPectively, which were higher than those in early lesion (Ⅰ or Ⅱ stage, 18.5% and 36.4% respectively). Furthermore, the patients with positive expression of MRP in gastric carcinoma tissues had shorter mean survival time and lower 5-year survival rate than that with negative eopression of MRP. Conclusion MRP plays an important role in the infiltration and metastasis of gastric and renal carcinoma and might contribute to the intrinsic drug - resistance in both carcinomas.

宣肺解毒方抑制IKK/NF-κB信号通路改善多重耐药铜绿假单胞菌肺炎大鼠肺损伤

目的探究宣肺解毒方抑制IKK/NF-κB信号通路改善多重耐药铜绿假单胞菌(MDR-PA)肺炎大鼠肺损伤的作用机制。方法84只大鼠随机分为7组:对照(control)组、模型(model)组、宣肺解毒方低、中、高剂量(XFJDF-low/medium/high dose)组、亚胺培南西司他丁(IPM)组以及NF-κB抑制剂(PDTC)组,每组12只。采用经口气管插管法建立MDR-PA肺炎大鼠模型。模型构建成功后,宣肺解毒方低、中、高剂量组分别给予相应剂量药物进行灌胃,亚胺培南西司他丁组给予IPM腹腔注射,而对照组和模型组大鼠给予等体积的生理盐水灌胃,每天2次,连续7 d;核因子κB(NF-κB)抑制剂组在模型构建前1 h、模型建立后12 h和24 h给予PDTC腹腔注射。观察大鼠的行为状态、体重变化、脾和胸腺指数、肺湿重/肺干重比例。通过HE染色评估肺组织病理学变化;TUNEL染色检测肺组织细胞凋亡;ELISA检测血清中的白介素1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、转化生长因子-β(TGF-β)和白介素10(IL-10)水平;比色法和硫代巴比妥酸(TBA)法等测定大鼠血清中的还原型谷胱甘肽(GSH)含量、丙二醛(MDA)含量、髓过氧化物酶(MPO)活性和总抗氧化能力(T-AOC);免疫组化法检测肺组织中NF-κBp65的表达;RT-qPCR技术分析肺组织IKKβ和NF-κBp65 mRNA的表达;Western blot技术测定肺组织中IKKβ、p-IKKβ、NF-κBp65、p-NF-κBp65蛋白的表达水平。结果与对照组相比,模型组大鼠饮食减少、毛发缺少光泽、反应迟钝、活动度降低、呼吸频率加快,并伴有杂音,体重显著降低(P<0.01);脾指数和胸腺指数显著升高(P<0.01);肺湿重/肺干重显著升高(P<0.01),肺组织肺泡腔分泌物增多、有大量炎性细胞浸润,肺组织凋亡细胞明显增多;血清中IL-1β、TNF-α、TGF-β、IL-10水平显著升高(P<0.01),MDA含量增加、MPO活性增强、GSH水平与T-AOC能力降低(P<0.01);肺组织IKKβ、NF-κBp65 mRNA表达量显著升高(P<0.01);肺组织p-IKKβ/IKKβ和p-NF-κBp65/NF-κBp65显著升高(P<0.01)。与模型组相比,干预组均能不同程度改善上述指标(P<0.05,P<0.01),其中以宣肺解毒方高剂量组和亚胺培南西司他丁组较为显著。结论宣肺解毒方可能通过抑制IKK/NF-κB信号通路改善MDR-PA肺炎大鼠肺损伤。

A Prospective Study on the Efficiency of Ciprofloxacin in Combination with Chloramphenicol against Multiple Antibiotics Resistant <i>Klebsiella pneumonia</i>

Pneumonia is the single largest infectious cause of death in children worldwide and also a form of an acute respiratory infection that affects the lung. The purpose of the study was to develop a new approach to treat antibiotic-resistant K. pneumoniae infection. This study aimed in quest of a drug to combine with ciprofloxacin, a broad spectrum antibiotic frequently used to treat lung infections. Methodology: A total of 23 lung infection bacterial samples were collected and studied against 14 antibiotics of different classes. The disk diffusion method was performed to determine synergy screening, MIC value, and qualitative toxicity analysis of ciprofloxacin and chloramphenicol combination. Results: After primary screening of antibiotic susceptibility, they were categorized into multidrug-resistant (MDR), extensively drug-resistant (XDR) and pan drug-resistant (PDR) pathogens where 9 isolates were MDR, 5 were XDR and 3 isolates were PDR. Furthermore, they were trialed in combination ciprofloxacin along with other 7 drugs in disk diffusion to explore the synergistic effect. The combination of ciprofloxacin and moxifloxacin, ciprofloxacin and chloramphenicol were found to be synergic. Then the MIC test was done for the combination ciprofloxacin and chloramphenicol. When the MIC result was generated, the MIC of the respective combination was analyzed. Furthermore, the fractional inhibitory concentration (FIC) was calculated and in accordance with the results of the FIC index, ciprofloxacin-chloramphenicol combination has shown value 0.4510 which revealed a synergistic effect against multi-drug resistant Klebsiella pneumoniae. Conclusion: Given these points, if the efficiency of this antibiotic can be accelerated from combination with other drugs, it might be lifesaving and cost effective as well.

Risk factors and mortality rates of carbapenem-resistant Gram-negative bacterial infections in intensive care units

Background The prevalence of hospital-acquired infections caused by carbapenem-resistant gram-negative bacteria(CRGNB)is increasing worldwide.Several risk factors have been associated with such infections.The present study aimed to identify risk factors and determine the mortality rates associated with CRGNB infections in intensive care units.Methods This retrospective case-control study was conducted at Erciyes University Hospital(Kayseri,Turkey)between January 2017 and December 2021.Demographic and laboratory data were obtained from the Infection Control Committee data and record system.Patients who had CRGNB infection 48–72 h after hospitalization were assigned to the case group,while those who were not infected with CRGNB during hospitalization formed the control group.Risk factors,comorbidity,demographic data,and mortality rates were compared between the two groups.Results Approximately 1449 patients(8.97%)were monitored during the active follow-up period;of those,1171 patients were included in this analysis.CRGNB infection developed in 14 patients(70.00%)who had CRGNB colonization at admission;in 162(78.26%)were colonized during hospitalization,whereas 515(54.56%)were not colonized.There was no significant difference in age,sex(male/female)or comorbidities.The total length of hospital stay was statistically significantly longer(P=0.001)in the case group(median:24[interquartile range:3–378]days)than the control group(median:16[interquartile range:3–135]days).The rates of colonization at admission(25.5%;vs.10.6%,P=0.001)and mortality(64.4%vs.45.8%,P=0.001)were also significantly higher in the cases than in the control group,respectively.In the univariate analysis,prolonged hospitalization,the time from intensive care unit admission to the development of infection,presence of CRGNB colonization at admission,transfer from other hospitals,previous antibiotic use,enteral nutrition,transfusion,hemodialysis,mechanical ventilation,tracheostomy,reintubation,central venous catheter,arterial catheterization,chest tube,total parenteral nutrition,nasogastric tube use,and bronchoscopy procedures were significantly associated with CRGNB infections(P<0.05).Multivariate analysis identified the total length of stay in the hospital(odds ratio[OR]=1.02;95%confidence interval[CI]:1.01 to 1.03;P=0.001),colonization(OR=2.19;95%CI:1.53 to 3.13;P=0.001),previous antibiotic use(OR=2.36;95%CI:1.53 to 3.62;P=0.001),intubation(OR=1.59;95%CI:1.14 to 2.20;P=0.006),tracheostomy(OR=1.42;95%CI:1.01 to 1.99;P=0.047),and central venous catheter use(OR=1.62;95%CI:1.20 to 2.19;P=0.002)as the most important risk factors for CRGNB infection.Conclusions Colonization,previous use of antibiotics,and invasive interventions were recognized as the most important risk factors for infections.Future research should focus on measures for the control of these parameters.

颅脑损伤继发革兰阴性菌肺炎的危险因素及经验性抗菌治疗药物的选择:回顾性病例-病例-对照研究

目的分析颅脑损伤患者继发多重耐药革兰阴性菌(multidrug-resistant Gram-negative bacteria,MDRGNB)肺炎的危险因素,考察革兰阴性菌(Gram-negative bacteria,GNB)的菌种构成和耐药性,为经验性抗菌治疗提供参考依据。方法回顾性分析我院2020年5月—2022年7月收治的颅脑损伤患者的临床资料,依据患者呼吸道GNB阳性情况,将继发GNB肺炎的患者纳入病例组,将无肺部临床感染指征或非GNB所致肺炎的患者纳入对照组。对于继发GNB肺炎的患者,依据病原菌耐药性将病例组进一步分为两个亚组,即MDRGNB感染组和非MDRGNB感染组,形成病例-病例-对照的分组模式。对比病例组与对照组临床资料的差异,将差异显著的变量纳入多因素非条件Logistic回归分析,分别筛选MDRGNB感染和非MDRGNB感染的独立危险因素。随后分别考察两个病例组的病原菌构成及耐药性。结果共纳入188例研究对象,其中对照组113例,MDRGNB感染组48例,非MDRGNB感染组27例。多因素Logisic回归分析显示,亚低温治疗(OR=6.380,95%CI=1.838~22.146,P=0.004)是非MDRGNB感染的独立危险因素。亚低温治疗(OR=5.419,95%CI=2.030~14.465,P=0.001)、机械通气时长(OR=1.095,95%CI=1.003~41.196,P=0.043)和使用碳青霉烯类抗菌药物(OR=2.900,95%CI=1.137~7.397,P=0.026)是MDRGNB感染的独立危险因素。非MDRGNB组共检出31株病原菌,以肺炎克雷伯菌为主(45.16%)。MDRGNB组共检出55株病原菌,以鲍曼不动杆菌为主(32.73%)。药敏试验结果显示,非MDRGNB组对氨苄西林/舒巴坦和替卡西林/棒酸的敏感率低于80.00%,对其他抗菌药物敏感率均大于80.00%。MDRGNB组对米诺环素和多黏菌素B的敏感率最高,分别为85.45%和100.00%,对其他抗菌药物的敏感率均低于30.00%。结论亚低温治疗与非MDRGNB感染和MDRGNB感染相关,机械通气时长和使用碳青霉烯类抗菌药物与MDRGNB感染相关。非MDRGNB感染组对大部分抗菌药物敏感性较好。对于MDRGNB感染患者,可考虑以米诺环素、替加环素或多黏菌素为基础的联合抗菌治疗方案。

新型β-内酰胺酶抑制剂药物研究进展

多重耐药革兰阴性菌的不断出现及流行严重限制了抗感染治疗用抗菌药物的选择,β-内酰胺酶的产生是其耐药的主要机制。因此,针对β-内酰胺酶开发的抑制剂也成为研究热点。近年来,已有多种新型β-内酰胺酶抑制剂药物问世或已投入临床使用。这些抑制剂的研发不仅为治疗多重耐药革兰阴性菌感染提供了新的希望,而且也为抗菌药物的再利用和研发提供了重要思路。本文将对这些抑制剂的化学结构、抗菌机制以及临床应用进行深入探讨,以期为临床用药提供更可靠的依据。

Aerosolized Amikacin as Adjunctive Therapy of Ventilator-associated Pneumonia Caused by Multidrug-resistant Gram-negative Bacteria： A Single-center Randomized Controlled Trial

Background： Aerosolized amikacin （AA） is a current option for the management of ventilator-associated pneumonia （VAP） caused by multidrug-resistant Gram-negative bacteria （MDR-GNB）, as it is reported that AA could increase the alveolar level of the drug without increasing systemic toxicity. This study aimed to evaluate the efficacy and safety of AA as an adjunctive therapy for VAP caused by MDR-GNB. Methods： In this single-center, double-blind study conducted in a 36-bed general Intensive Care Unit （ICU） in a tertiary hospital from June 2014 to June 2016, 52 ICU patients with confirmed MDR-GNB VAP were randomized to two groups （AA group, n - 27 and placebo group, n = 25）. Amikacin （400 rag, q8h） or saline placebo （4 ml, q8h） was aerosolized for 7 days. The attending physician determined the administration of systemic antibiotics for VAP. Patients were tbllowed up for 28 days. Bacteriological eradication, clinical pulmonary infection score （CP1S）, and serum creatinine were assessed on day 7 of therapy. New resistance to amikacin, cure rate of VAP, weaning rate, and mortality were assessed on day 28. Results： The baseline characteristics of patients in both groups were similar. At the end of the treatment, 13 of the 32 initially detected bacterial isolates were eradicated in AA group, compared to 4 of 28 in placebo group （41% vs. 14%, P - 0.024）. As for patients, 11 of 27 patients treated with AA and 4 of 25 patients treated with placebo have eradication （41% vs. 16%, P = 0.049）. The adjunction of AA reduced CPIS （4.2 ± 1.6 vs. 5.8 ± 2.1, P = 0.007）. New drug resistance to amikacin and the change in serum creatinine were not detected in AA group. No significant differences in the clinical cure rate in survivors （48% vs. 35%, P = 0.444）, weaning rate （48% vs. 32%, P = 0.236）, and mortality （22% vs. 32%, P = 0.427） were detected between the two groups on day 28. Conclusions： As an adjunctive therapy of MDR-GNB VAP, AA successfully eradicated existing MDR organisms without inducing new resistance to amikacin or change in serum creatinine. However, the improvement of mortality was not found.

Antibacterial efficacy of five medicinal plants against multidrug-resistant enteropathogenic bacteria infecting under-5 hospitalized children

OBJECTIVE： To evaluate in vitro antibacterial effectiveness of five medicinal plants used by an Indian aborigine, against 8 multidrug-resistant （MDR） enteropathogenic bacteria isolated from clinical samples of under-5 hospitalized children. METHODS： Antibiotic sensitivity patterns of eight clinically isolated strains of enteropathogenic bacteria, Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae, Salmonella paratyphi, S. typhi, Shigella dysenteriae, S. sonnei and Vibrio cholerae were assessed by disc-diffusion method. Antibacterial activities of 8 solvent-extracts of leaves and bark of five medicinal plants were monitored by the agar-well diffusion method. The microbroth dilution method was used to assess minimum inhibitory concentration （MIC） and minimum bactericidal concentration （MBC）. Qualitative phytochemical analyses of active plant extracts were carried out. RESULTS： Ethanol, ethyl acetate and methanol extracts of Holarrhena antidysenterica leaf tissue were most effective against 8 MDR pathogens in vitro. Similarly, acetone, ethanol and methanol extracts of Terminalia alata leaf tissue; chloroform, ethyl acetate and methanol extracts of Terminalia aquna leaf tissue and ethyl acetate, ethanol and methanol extracts of Paederia foetida leaf tissue were most effective in inhibiting in vitro growth of the 8 MDR enteropathogens. Ethyl acetate and methanol extracts of H. antidysenterica bark tissue; acetone, ethanol and methanol extracts of T. alata bark tissue and acetone, ethanol and methanol extracts of T. arjuna bark tissue were most effective in controlling enteropathogen growth. The minimum inhibitory concentration and minimum bactericidal concentration values of the 3 most antimicrobial leaf and bark extracts from the five plants were in the range of 1.56 to 50 mg/mL. CONCLUSION： These 5 plants exhibited in vitro control over a cohort of 8 enteropathogenic bacteria strains isolated from clinical samples.