Identification of factors affecting meropenem pharmacokinetics in critically ill patients: Impact of inflammation on clearance

IntroductionThe purpose of this study was to explore factors influencing meropenem pharmacokinetics (PKs) in critically ill patients by developing a population PK model and to determine the optimal dosing strategy.MethodsThis prospective observational study involved 12 critically ill patients admitted to the intensive care unit and treated with meropenem 1 g infused over 1 h every 8 h. Blood samples were collected on days 1, 2, and 5 immediately prior to dosing, and at 1, 2, 4, and 6 h after the start of infusion. Population PK parameters were estimated using nonlinear mixed-effects model software.ResultsMeropenem PK was adequately described using a two-compartment model. Typical values of total and inter-compartmental clearance were 9.30 L/h and 9.70 L/h, respectively, and the central and peripheral compartment volumes of distribution were 12.61 L and 7.80 L, respectively. C-reactive protein (CRP) was identified as significant covariate affecting total meropenem clearance. The probability of target attainment (PTA) predicted by Monte Carlo simulations varied according to the patients’ CRP. The PTA of 100% time above the minimum inhibitory concentration ≤2 mg/L for bacteria was achieved after a dose of 1 and 2 g infused over 4 h every 8 h in patients with CRP of 30 and 5 mg/dL, respectively.ConclusionThe findings of this study suggest that CRP might be helpful in managing meropenem dosing in critically ill patients. Higher doses and extended infusion may be required to achieve optimal pharmacodynamic targets.     

Biofilm-formation capability depends on environmental oxygen concentrations in Candida species

BackgroundAlthough oxygen concentrations inside of the human body vary depending on organs or tissues, few reports describe the relationships between biofilm formation of Candida species and oxygen concentrations. In this study, we investigated the biofilm-forming capabilities of Candida species under various oxygen conditions.MethodsWe evaluated the adhesion and biofilm formation of Candida albicans and C. tropicalis under aerobic, microaerobic (oxygen concentration 5%), or anaerobic conditions. We also examined how oxygen concentration affects adhesion/maturation by changing adhesion/maturation phase conditions. We used crystal violet assay to estimate the approximate biofilm size, performed microscopic observation of biofilm morphology, and evaluated adhesion-associated gene expression.ResultsThe adhered amount was relatively small except for a clinical strain of C. tropicalis. Our biofilm-formation analysis showed that C. albicans formed a higher-size biofilm under aerobic conditions, while C. tropicalis favored microaerobic conditions to form mature biofilms. Our microscopic observations were consistent with these biofilm-formation analysis results. In particular, C. tropicalis exhibited more hyphal formation under microaerobic conditions. By changing the adhesion/maturation phase conditions, we represented that C. albicans had favorable biofilm-formation capability under aerobic conditions, while C. tropicalis showed enhanced biofilm formation under microaerobic adhesion conditions. In good agreement with these results, the C. tropicalis adhesion-associated gene expression tended to be higher under microaerobic or anaerobic conditions.ConclusionsC. albicans favored aerobic conditions to form biofilms, whereas C. tropicalis showed higher biofilm-formation ability and promoted hyphal growth under microaerobic conditions. These results indicate that favorable oxygen conditions significantly differ for each Candida species.     

Review of the early reports of the epidemiological characteristics of the B.1.1.7 variant of SARS-CoV-2 and its spread worldwide

The variant B.1.1.7 of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the RNA virus causing the pandemic more than a year worldwide, was reported from United Kingdom (UK) in late December 2020. It was reported that mortality increases by 65% and transmissibility increases by 70%, which may result in an increase of reproduction number to 1.13-1.55 from 0.75-0.85. To analyze the global increasing trend of the variant B.1.1.7, we extracted results of B.1.1.7 from GISAID on May 11 and May 12, 2021, and conducted a dose-response regression. It took 47 days to reach 20% and 121 days to reach 50% among the sequence submitted from UK. In Korea, cases of B.1.1.7 have increased since the first report of three cases on December 28, 2020. Positive rate of B.1.1.7 in Korea was 21.6% in the week from May 9 to May 15, 2021. Detection rate of the variants is expected to increase further and new variants of SARS-CoV-2 are emerging, so a close monitoring and control would be maintained for months.     

Novel approach for rapid detection of extended spectrum β-lactamase and metalloid-β-lactamase using drug susceptibility testing microfluidic device (DSTM)

Background/purpose: Rapid detection of β-lactamases is important in a recent situation where resistant bacteria are increasing. By using the drug susceptibility testing microfluidic device (DSTM), rapid screening of extended spectrum β-lactamases (ESBLs) and metallo-β-lactamases (MBLs) has become possible.Methodsβ-lactams and β-lactamase inhibitors were pre-fixed in the DSTM for use. A bacterial suspension in Mueller-Hinton broth (McF 0.25) was introduced into the device, and the effects of β-lactamase inhibitor on morphological changes caused by β-lactam were evaluated after 3 h incubation.ResultsClinical isolates genetically confirmed to produce β-lactamase were used. Of the 84 ESBL-producing strains, 80 strains (95%) turned to be ESBL positive, and five strains (6%) of them MBL were positive as well as ESBL. Four strains (5%) were negative for both ESBL and MBL. Of the 24 MBL-producing strains, 23 strains (96%) were positive for MBL. All the 43 AmpC-producing strains were negative for both ESBL and MBL. Of the 156 ESBL- and MBL-nonproducing strains, 155 strains (99%) were negative for both ESBL and MBL, and one strain was positive for ESBL. With this method, the detection sensitivity was 95% and the specificity was 100% for ESBL, whereas the detection sensitivity was 96% and the specificity was 98% for MBL. These results were not significantly different from the results of the disc diffusion method.ConclusionThe DSTM method allows rapid detection of β-lactamases in 3 h and may be a useful replacement for the disc diffusion method.     

Molecular epidemiological analysis of Mycobacterium tuberculosis modern Beijing genotype strains isolated in Chiba Prefecture over 10 years

IntroductionThe prevalence of the phylogenetic groups of Mycobacterium tuberculosis Beijing genotype has been reported to be similar in different areas of Japan. However, recent reports from rural areas of Japan show a low prevalence of modern Beijing strains, suggesting that the distribution of modern Beijing strains may have changed recently. Therefore, multi-locus variable number of tandem repeats analysis (MLVA) and draft whole genome sequence (DWGS) analysis were carried out to investigate the prevalence of particular genotype strains.MethodsNine hundred and ninety modern Beijing strains were studied using minimum spanning tree (MST) analysis and neighbor-net analysis of MLVA and WGS data.ResultsAn MST of M. tuberculosis Beijing genotype strains reconstructed from 12 loci-MLVA data showed two large complexes with the J₁₂-0006 MLVA pattern. In one of the complexes, strains with the pECT07 pattern produced by 24 loci-MLVA and its SLVs were most prevalent. DWGS analysis was carried out for pECT07 and its SLV strains. Neighbor-net and MST analyses of the DWGS data showed that pECT07 and its SLV strains were grouped in separate clusters. When all the combinations of two of the tested strains were analyzed, MST analysis showed that only 9 (1.7%) of the 528 pairs of tested strains had 5 or less SNPs.ConclusionsThe results of this study suggested that pECT07 and its variants were prevalent among M. tuberculosis modern Beijing strains in Chiba Prefecture, but the prevalence of those strains may not have been due to an earlier large-scale latent outbreak.     

广东省新型冠状病毒肺炎无症状感染者流行病学特征分析

目的 对广东省首次报告为新型冠状病毒肺炎（COVID-19）无症状感染者个案流行病学特征进行分析。方法 采用追踪观察方法,对广东省2020年1月14日至3月31日首次报告为COVID-19无症状感染者的个案进行持续追踪观察,收集流行病学相关资料,分析其流行病学特征和转归及影响因素。结果 2020年1月14日至3月31日共报告325例COVID-19无症状感染者,其流行曲线与确诊病例流行曲线相似,出现两个峰,分别在1月27日至2月5日和3月17－26日。325例个案中,184例（占56.6%）后续转为确诊病例,为潜伏期无症状感染者,其年龄M为40岁,93.5%（172/184）的潜伏期无症状感染者在首次采样检测核酸阳性3 d内出现症状;141例（占43.4%）持续无症状,属于隐性感染者,占同期报告新型冠状病毒感染者的8.6%（141/1 642）,其年龄M为27岁,从首次采样检测阳性到出院时间M为14 d,90.8%（138/141）的隐性感染者在28 d内出院转集中隔离观察,从首次采样检测核酸阳性到末次采样检测阳性时间间隔最长73 d。隐性感染者关联的密切接触者检出阳性率为0.3%,潜伏期无症状感染者关联的密切接触者检出阳性率为2.2%。潜伏期无症状感染者和隐性感染者年龄、感染来源构成差异均有统计学意义（P<0.05）。高年龄组为首次报告为“COVID-19无症状感染者”转为确诊病例的危险因素,与0~19岁组比较,40~59岁、≥60岁均为无症状感染者转确诊的危险因素,OR值（95% CI）分别为2.730（1.380~5.402）和5.302（2.199~12.783）,P值分别为0.004和0.000。境内感染无症状感染者更易转为确诊病例（OR=7.121,P=0.000）。结论 新型冠状病毒感染者中存在无症状感染现象,潜伏期无症状感染者传染性可能强于隐性感染者,高年龄组、境内感染是无症状感染者转为确诊病例的危险因素,需引起关注,后续需要在人群中开展血清学调查,为防控策略制定提供依据。     

Economic impact of implementing decennial tetanus toxoid,reduced diphtheria toxoid and acellular pertussis (Tdap) vaccination in adults in the United States

BackgroundIn the United States, persons ≥11 years are recommended to receive one dose of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine, followed by decennial tetanus- and diphtheria-toxoid (Td) boosters. Many providers use Tdap instead of Td. We evaluated epidemiologic and economic impacts of replacing Td boosters with Tdap.MethodsWe used a static cohort model to examine replacing Td with Tdap over the lifetime of 4,386,854 adults ≥21 years. Because pertussis is underdiagnosed and true incidence is unknown, we varied incidence from 2.5 cases/100,000 person-years to 500 cases/100,000 person-years. We calculated vaccine and medical costs from claims data. We estimated cost per case prevented and per quality-adjusted life year (QALY) saved; sensitivity analyses were conducted on vaccine effectiveness (VE), protection duration, vaccine cost, disease duration, hospitalization rates, productivity loss and missed work. We did not include programmatic advantages resulting from use of a single tetanus-toxoid containing vaccine.ResultsAt lowest incidence estimates, administering Tdap resulted in high costs per averted case ($111,540) and QALY saved ($8,972,848). As incidence increased, cases averted increased and cost per QALY saved decreased rapidly. With incidence estimates of 250 cases/100,000 person-years, cost per averted case and QALY saved were $984 and $81,678 respectively; at 500 cases/100,000 person-years, these values were $427 and $35,474. In multivariate sensitivity analyses, assuming 250 cases/100,000 person-years, estimated cost per QALY saved ranged from $971 (most favorable) to $217,370 (least favorable).ConclusionsOur findings suggest that replacing Td with Tdap for the decennial booster would result in high cost per QALY saved based on reported cases. However, programmatic considerations were not accounted for, and if pertussis incidence, which is incompletely measured, is assumed to be higher than reported through national surveillance, substituting Tdap for Td may lead to moderate decreases in pertussis cases and cost per QALY.     

Reducing the urine collection rate could prevent hospital-acquired horizontal transmission of multidrug-resistant Pseudomonas aeruginosa

IntroductionMultidrug-resistant Pseudomonas aeruginosa (MDRP) is a waterborne pathogen that occasionally causes hospital-acquired infection in immunocompromised or critically ill patients. Urine is frequently collected to evaluate renal function or to perform hormonal examinations, but the procedure involves risk due to the possibility of healthcare workers with contaminated hands. Our objective was to evaluate the association between the urine collection and hospital-acquired horizontal transmission of MDRP.MethodsWe monitored the urine collection rate from 2011 to 2017, as part of ongoing efforts to reduce the need to collect urine. The urine collection rate and the frequency of isolation of MDRP, Methicillin resistant S. aureus (MRSA) and extended spectrum β-lactamases (ESBL)-producing E. coli were analyzed during the same period. PFGE and MLST were also performed to analyze the identity of 5 MDRP strains detected on the same ward in 2014–2015.ResultsThe urine collection rate was dramatically decreased from 4.8% in 2011 to less than 0.5% in 2017, because the isolation rate of MDRP was significantly positively associated (RR = 1.72, 95%CI:1.03–2.85) with the urine collection rate. Isolations of MRSA and ESBL-producing E. coli showed no significant. Molecular typing showed the PFGE patterns of 3 of 5 MDRP strains were closely related as did MLST (ST17), and the remaining 2 MDRP strains had different PFGE and MLST patterns (ST14, ST655). Our data implicated the urine collection as one of the causes of hospital-acquired MDRP infections.ConclusionsWe concluded that a reducing the urine collection rate could contribute to preventing hospital-acquired horizontal transmission of MDRP.