The occurrence of antimicrobial substances in toilet,sink and shower drainpipes of clinical units: A neglected source of antibiotic residues

Antibiotics represent one of the most important drug groups used in the management of bacterial infections in humans and animals. Due to the increasing problem of antibiotic resistance, assurance of the antibacterial effectiveness of these substances has moved into the focus of public health. The reduction in antibiotic residues in wastewater and the environment may play a decisive role in the development of increasing rates of antibiotic resistance. The present study examines the wastewater of 31 patient rooms of various German clinics for possible residues of antibiotics, as well as the wastewater of five private households as a reference.To the best of our knowledge, this study shows for the first time that in hospitals with high antibiotic consumption rates, residues of these drugs can be regularly detected in toilets, sink siphons and shower drains at concentrations ranging from 0.02?μg·L^?1 to a maximum of 79?mg·L^?1. After complete flushing of the wastewater siphons, antibiotics are no longer detectable, but after temporal stagnation, the concentration of the active substances in the water phases of respective siphons increases again, suggesting that antibiotics persist through the washing process in biofilms. This study demonstrates that clinical wastewater systems offer further possibilities for the optimization of antibiotic resistance surveillance.     

One Health Genomic Analysis of Extended-Spectrum β-Lactamase‒Producing Salmonella enterica,Canada, 2012‒2016

Extended-spectrum β-lactamases (ESBLs) confer resistance to extended-spectrum cephalosporins, a major class of clinical antimicrobial drugs. We used genomic analysis to investigate whether domestic food animals, retail meat, and pets were reservoirs of ESBL-producing Salmonella for human infection in Canada. Of 30,303 Salmonella isolates tested during 2012–2016, we detected 95 ESBL producers. ESBL serotypes and alleles were mostly different between humans (n = 54) and animals/meat (n = 41). Two exceptions were bla_SHV-2 and bla_CTX-M-1 IncI1 plasmids_, which were found in both sources. A subclade of S. enterica serovar Heidelberg isolates carrying the same IncI1-bla_SHV-2 plasmid differed by only 1–7 single nucleotide variants. The most common ESBL producer in humans was Salmonella Infantis carrying bla_CTX-M-65, which has since emerged in poultry in other countries. There were few instances of similar isolates and plasmids, suggesting that domestic animals and retail meat might have been minor reservoirs of ESBL-producing Salmonella for human infection.     

儿科临床下呼吸道感染病原菌及其耐药性分析

目的对临床痰标本分离菌进行耐药性监测,了解儿科临床下呼吸道感染病原菌的构成及耐药情况,为临床合理用药提供依据.方法采用回顾性方法对本院2002年1月～2003年12月临床痰培养及药物敏感试验结果进行统计、分析.结果1135份痰标本中分离出细菌521株,以革兰阴性菌为主,克雷伯菌和大肠埃希菌分别为其前一、二位,其中产ESBLs菌株中肺炎克雷伯菌位居第一,产ESBLs大肠埃希菌位列第二;革兰阳性菌中耐甲氧西林菌株中MRSE占第一位.所监测的19种抗生素中18种抗生素有不同程度的耐药.产ESBLs菌株较不产ESBLs菌株、耐甲氧西林表皮葡萄球菌(MRSE)比甲氧西林敏感的表皮葡萄球菌(MSSE)的耐药率明显升高.产ESBLs菌株对第三代头孢菌素的耐药率已达到83%以上.万古霉素及亚胺培南分别成为治疗MRSE及产ESBLs菌株的首选.对喹诺酮类抗生素的耐药率较低可能与儿科使用较少有关.结论下呼吸道感染病原菌中产ESBLs菌株所占比例较高,应引起高度重视.定期进行细菌耐药性监测对提高诊疗水平是十分必要的.     

Pharmacokinetics of cefmetazole in plasma,peritoneal fluid,peritoneum, and subcutaneous adipose tissue of patients scheduled for lower gastrointestinal surgery: Dosing considerations based on site-specific pharmacodynamic target attainment

IntroductionCefmetazole (CMZ) has gained interest as a carbapenem-sparing alternative to the epidemic of extended-spectrum β-lactamase (ESBL)-producing Enterobacterales (ESBL-E). In this study, we investigated the pharmacokinetics (PK) of CMZ in plasma, peritoneal fluid, peritoneum, and subcutaneous adipose tissue to assess the dosing regimen needed to achieve pharmacodynamic (PD) goals at the target site.MethodsPatients scheduled for elective lower gastrointestinal surgery were intravenously administered CMZ. Plasma, peritoneal fluid, peritoneum, and subcutaneous adipose tissue samples were collected after CMZ infusion and during the surgery, and CMZ concentrations were measured. The non-compartmental and compartmental PK parameters were estimated and used to evaluate site-specific PD target attainment.ResultsA total of 38 plasma, 27 peritoneal fluid, 36 peritoneum, and 38 subcutaneous adipose tissue samples were collected from 10 patients. The non-compartmental PK analysis revealed the ratios of the mean area under the drug concentration-time curve (AUC_0–3.5 h) of peritoneal fluid-to-plasma, peritoneum-to-plasma, and subcutaneous adipose tissue-to-plasma were 0.60, 0.36, and 0.11, respectively. The site-specific PD target attainment analyses based on the breakpoints for ESBL-E per the Japanese surgical site infection (SSI) surveillance (MIC₉₀ = 8 mg/L) revealed that 2 g CMZ every 3.5 h achieved desired bactericidal effect at all sites and 2 g CMZ every 6 h achieved PD goals at peritoneum and peritoneal fluid.ConclusionThese findings clarify the PK of CMZ in abdominal tissues and could help decide optimal dosing regimens to treat intra-abdominal infection and prophylaxis of SSI.     

Comparative genetic analysis of the antimicrobial susceptibilities and virulence of hypermucoviscous and non-hypermucoviscous ESBL-producing Klebsiella pneumoniae in Japan

BackgroundHypermucoviscous (HMV) Klebsiella pneumoniae produces large amounts of capsular polysaccharides, leading to high mortality. Since extended spectrum beta-lactamase (ESBL)-producing HMV K. pneumoniae strains have increased in Japan, we investigated and compared the antimicrobial susceptibilities and genetic characteristics of HMV and non-HMV ESBL-producing K. pneumoniae.MethodsWe investigated 291 ESBL-producing K. pneumoniae collected between 2012 and 2018, and in them 54 HMV strains were identified and comparable 53 non-HMV strains were selected. Then, ESBL gene detection, plasmid replicon typing, and virulence gene detection were done by PCR amplification.ResultsAlmost all of the HMV K. pneumoniae strains possessed uge (98.1%), wabG (96.3%), rmpA (94.4%), iucA (79.6%), fimH (70.4%), iroB (70.4%), and peg-344 (70.4%). These genes were found less frequently in non-HMV strains (uge 20.8%, wabG 83.0%, rmpA 7.5%, iucA 3.8%, fimH 9.4%, iroB 5.7%, and peg-344 1.9%). K2 capsule type (40.7%) was most common in HMV strains. HMV strains showed higher resistance to cefepime (p = 0.001) and piperacillin/tazobactam (p = 0.005) than non-HMV strains. CTX-M-15 (75.9%, 60.4%) was the dominant ESBL type in both HMV and non-HMV strains, and the most common plasmid replicon type was IncFII (52.1%) in CTX-M-15-producing strains.ConclusionsWe found that HMV strains had more virulence genes and showed higher resistance to antibiotics than non-HMV strains. The most common capsule type was K2. CTX-M-15 was the most common type of ESBL gene in both HMV and non-HMV strains in Japan. The FII plasmid might be related to the spread of CTX-M-15 among K. pneumoniae strains.     

Exploration of the protein-dependent mechanism of Lactobacillus crispatus GAI98322 to prevent recurrent cystitis

ObjectivesTo elucidate the mechanism of Lactobacillus crispatus (L. crispatus) suppositories to prevent patients from recurrent cystitis (RC), independent from viable-Lactobacilli-bacteria- and acid-dependent ones such as hydrogen peroxide and lactate.MethodsWe used the GAI98322 strain of L. crispatus in all experiments and pH-matched.cell-free culture supernatant of L. crispatus (CFCS) was collected. The growth inhibitory activity and the biofilm formation inhibitory activity of the CFCS against uropathogenic Escherichia coli (UPEC), Extended Spectrum beta (β) Lactamase producing (ESBL+) UPEC, and Pseudomonas aeruginosa (P. aeruginosa) was assessed by agar-disk diffusion tests and crystal violet assay. Also, CFCS was subjected to mass spectrometry to specify ingredients.ResultsThe CFCS suppressed the proliferation of E. coli, ESBL + E. coli, and P. aeruginosa. Also, the CFCS at a concentration of 40% significantly impeded the biofilm formation of these three bacteria. The aggregation-promoting factor and Lysin was detected from CFCS.ConclusionsThe cell-free supernatant from the GAI98322 strain of L. crispatus inhibits the growth/biofilm formation of broad pathogens by aggregation promoting factor and lysin, which may prevent hosts from RC regardless of the antimicrobial resistance of the pathogens and even under pH modulation.