Infection and Drug Resistance最新文献

Background: Klebsiella pneumoniae MDR/XDR constitutes a difficult to treat bacteria in a number of infections as there are few therapeutic options. Promising drugs in such cases can be cefiderocol, aztreonam and ceftazidime/avibactam or meropenem/vaborbactam.

Case presentation: A 72-year-old female patient with sepsis caused by KP NDM, OXA 48 was admitted to the Intensive Care Unit, immediately after an emergency graftectomy (of a recently transplanted kidney) complicated with bleeding. Because of suspicion of intra-abdominal infection, a broad-spectrum empirical antibiotic therapy was initiated (meropenem, vancomycin, colistin). The patient underwent an abdominal revision 48 hours after admission. On the 3rd day of hospitalization, diagnosis of a septic shock with etiology of KP NDM, OXA 48 was made. The strain had sensitivity to a colistin and a cefiderocol. On 13th day in the ICU a relaparotomy was performed. Again, KP strains with sensitivity to cefiderocol only, were cultured from intra-abdominal fluid. Aztreonam, in combination with meropenem/vaborbactam, were included in the treatment and were used together with colistin and tigecycline. In the following days, the inflammatory markers decreased slightly, but the patient's general condition did not improve. On day 27 ceftazidime/avibactam and aztreonam were added, while colistin, meropenem/vaborbactam and fosfomycin were discontinued. On 37th day of hospitalization, cefiderocol became available in hospital and was included in the treatment. Cefiderocol monotherapy was continued for 8 days. After 4 days of cefiderocol treatment, the inflammatory markers CRP and PCT decreased and a significant improvement in patient's condition were observed. On day 56, the patient was transferred to another department.

Conclusion: A surgical debridement of a source infection, and usage of meropenem/vaborbactam or ceftazidime/avibactam together with aztreonam and colistin allowed survival of the patient but not full recovery. Ultimately, only the cefiderocol monotherapy was effective in treatment of the patient with septic shock of KP NDM OXA 48 etiology.

Background: RSV is a common seasonal cause of respiratory infections in children and potentially adults and is considered a major cause of mortality and morbidity. While several studies on RSV have been conducted in Saudi Arabia, none have specifically focused on the southwestern region, where distinct climatic and demographic factors may influence RSV pattern. The current study aims to describe five years of experience with RSV cases among hospitalized patients and factors associated with intensive care admission from a tertiary hospital.

Materials and methods: The study adopts a retrospective observational design, focusing on suspected respiratory infection cases confirmed by rapid RSV antigen tests from 2015 to 2020. Data including age, sex, comorbidities, and outcomes were collected from a tertiary hospital's medical records and microbiology laboratory files. Data were analyzed using a t-test and chi-square test.

Results: Among 195 participants, primarily pediatric, monthly, and yearly admissions varied. Monthly variations revealed a U-shaped pattern with most cases reported during January, with a decline in 2020. Oxygen support was required for 40% of cases, and comorbidities were observed in 49.23%. Associations between ICU admission and factors like age, gestational age, ventilation, comorbidities, and length of stay were significant.

Conclusion: RSV infection is one of the important causes of morbidity and intensive care admission among infants and young children in Saudi Arabia. As reported by others, the seasonality of RSV is evident. Despite higher prevalence in a younger population, physicians should consider RSV in adults and older patients. Further national studies are required for a better estimation of the RSV burden on the country.

Tuberculous spondylitis following percutaneous vertebroplasty or kyphoplasty is rare. In this, we report a rare case of tuberculous spondylitis diagnosed after percutaneous vertebroplasty (PVP). A 69-year-old female sought came to our department with a history of chest and back pain from the last two months accompanied by weakness in both lower limbs. The patient underwent two vertebroplasty procedures at a local hospital within two years for compression fractures of the lumbar and thoracic spine. Due to continuous lower back pain following PVP surgery, along with the worsening back pain weakness in both lower limbs over the past 2 months, the patient presented to our hospital for the treatment. Radiological imaging showed long bone destruction in the L1, L2, and T12 vertebrae, accompanied by the formation of numerous paraspinal abscesses. The serum T-SPOT test yielded a positive result. A sample was taken from a paravertebral abscess for TB DNA testing (GeneXpert MTB/RIF assay) under the guidance of CT, which demonstrated the patient was infected with a non-drug-resistant strain of TB. The patient underwent surgical treatment via a combined anterior and posterior approach. The histological examination of the excised tissue revealed evidence of tuberculosis, characterized by granulomatous inflammation and sheet necrosis. After taking anti tuberculosis drugs for 12 months, the patient recovered without any sequelae. Spinal tuberculosis and osteoporotic vertebral compression fractures are similar in clinical and radiological aspects. Spinal surgeons should consider the entity of this disease to avoid misdiagnosis or complications. After diagnosis of spinal tuberculosis after vertebral augmentation surgery, early surgical intervention and anti-tuberculosis treatment should be carried out immediately.

Objective: Ceftazidime-avibactam (CZA) is a novel β-lactam/β-lactamase inhibitor with activity against carbapenem-resistant Klebsiella pneumoniae (CRKP) that produce Klebsiella pneumoniae carbapenemase (KPC). In this study, we report the first cases of CZA resistance to develop during treatment of CRKP infections and identify the resistance mechanism.

Methods: APB/EDTA and NG-Test CARBA5 were used to detect the production of carbapenemase, whole-genome sequencing (WGS) and conjugation experiment were used to identify potential resistance mechanisms of CZA-susceptible (HX1032) and -resistant (HX1192) K. pneumoniae isolates.

Results: HX1192 K. pneumoniae was not recognized by APB/EDTA and NG-Test CARBA5 phenotypic assays, WGS revealed it carrying a novel KPC variant, KPC-179, molecular analysis highlighted a G394A mutation, and an ATC insertion at 543 in the bla_KPC-2 gene, resulting in an A133T substitution and insertion of the amino acid S at Ambler position 183 in the protein sequence. Remarkably, this mutation restored susceptibility of imipenem (MIC = 0.25 mg/L).

Conclusion: Our study highlights the importance of monitoring susceptibility during CZA treatment and accurately detecting KPC variants.

Background: Klebsiella michiganensis is an emerging human pathogen that causes nosocomial infections. Its prevalence and spread in the environment should not be ignored. This study identified and characterized Klebsiella michiganensis co-harboring bla _KPC-2 and TmexCD2-ToprJ2 in hospital wastewater samples.

Methods: Twelve K. michiganensis strains were isolated from wastewater samples collected at a tertiary hospital in Beijing, China. The genomic characteristics of K. michiganensis strains were analyzed using whole-genome sequences, providing information on the comparison between the genome of K. michiganensis strains and the reference genome, antibiotic resistance genes (ARGs), virulence genes, secretion systems, and mobile genetic elements (plasmids, insertion sequences [ISs], and prophages).

Results: Genome analysis showed that the twelve multi-drug resistant (MDR) strains carried a variety of ARGs and virulence genes, as well as four macromolecular secretion systems (T1SS, T2SS, T5aSS, T5bSS, and T4aP). The genetic environments of both the TmexCD2-ToprJ2 gene cluster and bla _KPC-2 gene contained ISs. The plasmids carrying TmexCD2-ToprJ2 gene cluster of nine strains in clade 1 and two strains in clade 2 were annotated as IncR plasmid and rep_cluster_1254 type, respectively. The plasmids carrying bla _KPC-2 in 10 strains in clade 1 were identified as IncU, and the plasmids carrying bla _KPC-2 in the k11 and k12 strains in clade 2 were IncU and IncX6. The phylogenetic tree and heatmap revealed that the secretion system of type VI (T6SSi) existed in 10 strains in clade 1, and Type IV (T4SS) only existed in the k11 strain in clade 2. In addition, K. michiganensis strains carried 13 plasmids, 14 ISs, and 138 prophages.

Conclusion: In this study, the whole genome sequencing demonstrated the diversity of K. michiganensis genome despite 12 K. michiganensis strains from a hospital wastewater, which lays the foundation for further genetic research and drug resistance gene transmission.

Background: To compare the clinical characteristics of symptoms and laboratory findings across SARS-CoV-2 variants (Wild-type, Alpha, Delta, Omicron) and assess the effectiveness of COVID-19 vaccines in preventing symptoms and laboratory abnormalities.

Methods: We conducted a retrospective cohort study of individuals with SARS-CoV-2 infection at Beijing Ditan Hospital, Capital Medical University. Patients were grouped by the SARS-CoV-2 variant (Wild-type, Alpha, Delta, Omicron) based on whole-genome sequencing. Thirteen symptoms and 22 laboratory indices were compared across variants, and Omicron patients were further analyzed by vaccination status with generalized estimating equations (GEE) model.

Results: One thousand four hundred and thirteen participants were included for the analysis as following: Wild-type group (N=322), Alpha group (N=67), Delta group (N=98), and Omicron group (N=926). Omicron patients showed the highest proportion (30.1%) of respiratory symptoms across groups. Patients displayed normal laboratory manifestation, except for inflammatory markers, coagulation function index and glucose. Meanwhile, the Omicron variant was featured by higher inflammatory biomarkers (serum amyloid A protein [SAA] and C-reactive protein [CRP]). In addition, Omicron patients with three or more vaccine doses had fewer symptoms and higher values of SAA and CRP compared to those with fewer than three doses. Results of GEE showed, when compared with ≤ 1 vaccine dose, red blood cell count, white blood cell count, neutrophil count, platelet count, haemoglobin, and C-reactive protein in patients with ≥ 3 doses of vaccine significantly increased; while aspartic transaminase, creatine kinase, blood urea nitrogen, activated partial thromboplastin time, prothrombin time and thrombin time dramatically decreased, respectively.

Conclusion: Omicron variant resulted in abnormal inflammatory response. Individuals with three or more vaccine doses are more likely to experience fewer symptoms and have stronger protection against the virus. This study highlights key differences in symptom onset and laboratory profiles across SARS-CoV-2 variants, reinforcing the importance of three vaccine doses in providing strong protection against the Omicron variant.

Objective: To analyze the prevalence and molecular characteristics of 16S rRNA methylase genes in clinical isolates of carbapenem-resistant Enterobacterales, for clinical doctors provide a reference basis for the rational use of drugs.

Methods: The Enterobacterales isolated from our hospital from 2020 to 2022 were selected and identified by VITEK 2 Compact automatic bacterial identification instrument. Resistance genes were detected by polymerase chain reaction.

Results: A total of 180 carbapenem-resistant Enterobacterales were isolated, of which 158 (87.8%) were resistant to at least one aminoglycoside. The resistance rates to gentamicin, tobramycin and amikacin were 85.0%,82.8% and 54.4%, respectively. Compared with 16S rRNA methyltransferase negative isolates, the positive isolates were more sensitive to trimethoprim-sulfamethoxazole, tetracycline and minocycline, but had higher resistance rates to aztreonam, tobramycin, gentamicin, amikacin and ciprofloxacin. The resistance rates of 16S rRNA methyltransferase gene positive strains to most commonly used antibiotics were more than 80%. But the rates for colistin and tigecycline were less than 10%. There were 114 strains (63.3%) positive for 16S rRNA methyltransferase genes, mainly rmtB, accounting for 70.2%. The positive rates of other armA, rmtA and armA+rmtB genes were 22.8%, 4.4% and 2.6%, respectively. No rmtC, rmtD, rmtE and npmA genes were detected. In addition, 175 of the 180 carbapenem-resistant Enterobacterales carried at least one carbapenemase genes. The bla_KPC was the main one (115, 65.7%). There were 111 (61.7%) strains carried both carbapenemase and 16S rRNA methyltransferase genes, simultaneously. Compared with 16S rRNA methyltransferase negative strains, the positive strains carried more bla_KPC genes and less bla_NDM genes, with P values of 0.034 and 0.003, respectively.

Conclusion: bla_KPC and rmtB genes are the main resistance mechanisms of Enterobacterales to carbapenems and aminoglycosides in our hospital. It is necessary to strengthen the detection of multi-drug resistant strains to provide scientific basis for clinical rational drug use.

Background: Over the past years, there has been a significant increase in the incidence of Mycoplasma pneumoniae (MP) infections, particularly among pediatric patients, nationwide. An emerging body of research has established a link between dysbiosis of the host microbiome and the metabolic functioning of the host, which contributes to the development of respiratory diseases.

Methods: A total of 25 children were included in the study, comprising 15 pneumonia patients and 10 healthy children. Stool samples were collected from all participants to analyze the 16S ribosomal RNA (16S rRNA) gene, while serum samples were prepared for untargeted metabolomics to qualitatively and quantitatively assess short-chain fatty acids.

Results: The gut microbial composition of individuals with Mycoplasma pneumoniae pneumonia (MPP) exhibited significant differences compared to healthy children. Notably, diseased children demonstrated higher microbial diversity and an enrichment of opportunistic pathogens, such as Erysipelatoclostridium and Eggerthella. Analysis revealed elevated levels of two specific short-chain fatty acids, namely acetic acid and isobutyric acid, in the MPP group, suggesting their potential as biomarkers for predicting MP infection. Metabolomic signature analysis identified a significant increase in major classes of glycerophospholipids in the MPP group. Moreover, we identified a total of 750 significant correlations between gut microbiota and circulating serum metabolites. MPP enriched genera Erysipelatoclostridium and Eggerthella, exhibited negative associations with indole-3-butyric acid. Additionally, Eggerthella showed a positive correlation with inflammatory metabolites LPC (18:0).

Discussion: Collectively, these findings provide novel insights into the selection of potential biomarkers and the pathogenesis of MPP in children based on the gut microbiota and systemic circulating metabolites.

Objective: Interstitial lung diseases (ILDs) comprise a heterogeneous group of disorders characterized by inflammation and fibrosis of the pulmonary interstitium, posing significant challenges in identifying their underlying causes. Pneumocystis pneumonia (PCP) is the leading cause of ILD in people living with HIV (PLWH). In individuals with connective tissue diseases, ILD is a frequent complication with significant morbidity and mortality.

Methods: A case is presented that details the intricate diagnostic process of rapidly progressive interstitial lung disease (RP-ILD).

Results: The patient initially presented with clinical features consistent with ILD, including progressive respiratory symptoms and radiological findings typical of pulmonary inflammation. Coupled with a positive HIV screening result, these findings led to an initial misdiagnosis of PCP, a common opportunistic infection in PLWH. However, despite standard anti-PCP treatment, the patient's condition did not improve, prompting further diagnostic evaluations. Subsequent investigations revealed the presence of serum anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody, a biomarker strongly associated with rapidly progressive ILD in clinically amyopathic dermatomyositis (CADM).

Conclusion: This case report offers a novel perspective on the diagnostic process of ILD, particularly emphasizing the importance of distinguishing false-positive antibodies caused by autoimmune diseases in the context of positive HIV screening tests, thereby improving the accuracy of RP-ILD diagnosis and mitigating the mortality burden associated with this condition.

Purpose: Gram-negative bloodstream infection (GNBI) poses a serious threat to critically ill patients. This retrospective study aimed to uncover drug resistance of pathogens and the GNBI effect on in-hospital death and distinguish death risk factors in a medical intensive care unit (ICU).

Patients and methods: A retrospective study of all GNBI patients in the medical ICU of the Third Xiangya Hospital over 9 nine years was conducted. Blood samples were performed by a BACTEC 9240 system, MALDI-TOF MS, Bruker and Vitek-2 system. Logistic regression was used for analyzing risk factors for death.

Results: Seventy-five episodes of GNBI developed in 68 (1.4%) out of 4954 patients over a span of 9 years. The most frequently isolated bacterium was Klebsiella pneumoniae, with the lungs as the predominant source of GNBI. The resistance rate of Gram-negative bacteria to polymyxin B was 11.6% after excluding those intrinsically resistant non-fermentative bacteria. All Enterobacter spp. were susceptible to ceftazidime/avibactam. Thirty-three (48.5%) patients underwent inappropriate empirical antibiotic treatment and 48 (70.6%) patients died during the hospitalization. Multivariate logistic regression analysis identified that lymphocyte count at GNBI onset ≤0.5×10⁹/L, invasive mechanical ventilation, and septic shock were related to in-hospital death. Body mass index ≥23 and appropriate empirical antibiotic use after GNBI were negatively associated with in-hospital death.

Conclusion: GNBI was a frequent complication among patients in the medical ICU. This study underscored the presence of diverse factors that either heightened or attenuated the risk of in-hospital death.