Failure of ceftazidime/avibactam experimental therapy in the treatment of Klebsiella pneumoniae ST11 co-producing NDM-1 and OXA-48 carbapenemases infection.

Carbapenem-resistant organisms (CRO) represent a significant threat because of their widespread in hospital settings, difficult-to-treat, and association with high morbidity and mortality rates. Data on the efficacy of ceftazidime/avibactam (CAZ-AVI) among patients infected with CRO in Iran are lacking. Herein, we report a case of a 91-year-old man with infection caused by extensively drug-resistant ST11 co-harbouring blaNDM and blaOXA-48-like strain from seven isolates. During ICU hospitalization, 10 different antibiotics were prescribed to the patient, and CAZ-AVI was experimentally prescribed in combination with tobramycin and tigecycline to the patient for the first time in the teaching hospitals of Isfahan City. The patient died on the 56th day of hospitalization. The present study revealed that the use of CAZ-AVI should be limited to targeted therapy after susceptibility results and minimum inhibitory concentration values are available to the treating clinicians and not be used for empirical therapy of patients with an infection caused by CRO, underscoring the urgent need for stringent policies for antibiotic stewardship to preserve the activity of novel ß-lactam/ß-lactamase inhibitors.

High prevalence of polymyxin-heteroresistant carbapenem-resistant Klebsiella pneumoniae and its within-host evolution to resistance among critically ill scenarios.

PURPOSE: We aimed to explore the prevalence and within-host evolution of resistance in polymyxin-heteroresistant carbapenem-resistant Klebsiella pneumoniae (PHR-CRKP) in critically ill patients. METHODS: We performed an epidemiological analysis of consecutive patients with PHR-CRKP from clinical cases. Our study investigated the within-host resistance evolution and its clinical significance during polymyxin exposure. Furthermore, we explored the mechanisms underlying the dynamic evolution of polymyxin resistance at both subpopulation and genetic levels, involved population analysis profile test, time-killing assays, competition experiments, and sanger sequencing. Additionally, comparative genomic analysis was performed on 713 carbapenemase-producing K. pneumoniae strains. RESULTS: We enrolled 109 consecutive patients, and PHR-CRKP was found in 69.7% of patients without previous polymyxin exposure. 38.1% of PHR-CRKP isolates exhibited polymyxin resistance and led to therapeutic failure in critically ill scenarios. An increased frequency of resistant subpopulations was detected during PHR-CRKP evolution, with rapid regrowth of resistant subpopulations under high polymyxin concentrations, and a fitness cost in an antibiotic-free environment. Mechanistic analysis revealed that diverse mgrB insertions and pmrB hypermutations contributed to the dynamic changes in polymyxin susceptibility in dominant resistant subpopulations during PHR evolution, which were validated by comparative genomic analysis. Several deleterious mutations (e.g. pmrBLeu82Arg, pmrBSer85Arg) were firstly detected during PHR-CRKP evolution. Indeed, specific sequence types of K. pneumoniae demonstrated unique deletions and deleterious mutations. CONCLUSIONS: Our study emphasizes the high prevalence of pre-existing heteroresistance in CRKP, which can lead to polymyxin resistance and fatal outcomes. Hence, it is essential to continuously monitor and observe the treatment response to polymyxins in appropriate critically ill scenarios.

Ertapenem plus meropenem combination treatment in carbapenem-resistant Klebsiella pneumoniae bacteremia: an analysis of 53 cases.

Herein, we aimed to describe the outcomes of patients with blood stream infections due to carbapenem-resistant Klebsiella pneumoniae (CR-Kp) who received ertapenem plus meropenem combination treatment (EMCT). A total of 53 patients with culture proven CR-Kp bacteremia treated with ertapenem + meropenem were included. The patients with secondary bacteremia due to urinary tract infection exhibited a significantly lower 1-month mortality (OMM), particularly in those with microbiological eradication and those with end-of-treatment success. Salvage EMCT resulted in 49% 1-month survival.

Severe COVID-19-associated sepsis is different from classical sepsis induced by pulmonary infection with carbapenem-resistant klebsiella pneumonia (CrKP).

PURPOSE: COVID-19 is also referred to as a typical viral septic pulmonary infection by 2019-nCoV. However, little is known regarding its characteristics in terms of systemic inflammation and organ injury, especially compared with classical bacterial sepsis. This article aims to investigate the clinical characteristics and prognosis between COVID-19-associated sepsis and classic bacterial-induced sepsis. METHODS: In this retrospective cohort study, septic patients with COVID-19 in the intensive care unit (ICU) of a government-designed therapy center in Shenzhen, China between January 14, 2020 and March 10, 2020, and septic patients induced by carbapenem-resistant klebsiella pneumonia (CrKP) admitted to the ICU of the Second People's Hospital of Shenzhen, China between January 1, 2014 and October 30, 2019 were enrolled. Demographic and clinical parameters including comorbidities, critical illness scores, treatment, and laboratory data, as well as prognosis were compared between the two groups. Risk factors for mortality and survival rate were analyzed using multivariable logistic regression and survival curve, respectively. RESULTS: A total of 107 patients with COVID-19 and 63 patients with CrKP were enrolled. A direct comparison between the two groups demonstrated more serious degrees of primary lung injury following 2019-nCoV infection (indicated by lower PaO2/FiO2), but milder systemic inflammatory response, lower sequential organ failure assessment score and better functions of the organs like heart, liver, kidney, coagulation, and circulation. However, the acquired immunosuppression presented in COVID-19 patients was more severe, which presented as lower lymphocyte counts (0.8×109/L vs. 0.9×109/L). Moreover, the proportion of COVID-19 patients treated with corticosteroid therapy and extracorporeal membrane oxygenation was larger compared with CrKP patients (78.5% vs. 38.1% and 6.5% vs. 0, respectively) who required less invasive mechanical ventilation (31.6% vs. 54.0%). The incidence of hospitalized mortality and length of ICU stay and total hospital stay were also lower or shorter in viral sepsis (12.1% vs. 39.7%, 6.5 days vs. 23.0 days and 21.0 days vs. 33.0 days, respectively) (all p < 0.001). Similar results were obtained after being adjusted by age, gender, comorbidity and PaO2/FiO2. Lymphocytopenia and high acute physiology and chronic health evaluation II scores were common risk factors for in-hospital death. While the death cases of COVID-19 sepsis mostly occurred at the later stages of patients' hospital stay. CONCLUSION: Critical COVID-19 shares clinical characteristics with classical bacterial sepsis, but the degree of systemic inflammatory response, secondary organ damage and mortality rate are less severe. However, following 2019-nCoV infection, the level of immunosuppression may be increased and thus induce in more death at the later stage of patients' hospitalstay.

Carbapenem-resistant Klebsiella pneumonia infection outbreak in a tertiary urology clinic: analysis of influencing factors with a controlled trial

Background/aim: Carbapenem-resistant Klebsiella pneumoniae (CR-KP) infections encountered in urology patients differentiate from infections caused by other factors, both in respect to prophylaxis and treatment stage, and require a special approach. We aimed to analyse the predisposing factors and the antibiotherapies for CR-KP infection outbreak in a tertiary urology clinic. Materials and methods: There were 75 patients in the CR-KP positive group (Group I) and 146 patients in the CR-KP negative group (Group II). Analysis of the predisposing factors for CR-KP infection and comparison of the reinfection rate and the antibiotherapies in the 2 groups were the endpoints. Results: In the first group, age, comorbidity, previous antibiotic use, and nephrostomy tube rates were higher (P = 0.015, P = 0.001, P = 0.004, and P < 0.001, respectively). In the second group, open urological surgery rate, and the proportion of patients presenting with flank pain, lower urinary tract symptoms, and haematuria were higher (P = 0.029, P < 0.001, P < 0.001, and P = 0.007). In the first group, the proportion of patients treated with transurethral bladder tumour resection was higher, whereas, percutaneous nephrolithotomy was higher in the second group (P = 0.045 for both). While hospitalization and Foley catheterization duration were longer in the first group (P < 0.001 for both), double J stent and nephrostomy duration were longer in the second group (P < 0.001 and P = 0.005). Mean leukocyte count at admission was higher in the first group (P < 0.001). Conclusion: Advanced age, comorbidities, previous antibiotic use, and prolonged Foley catheterization duration are predisposing factors for this infection in the urology department. Two-week administration of combination antibiotic regimens containing carbapenem were effective for the treatment of this infection.

Molecular mechanisms responsible KPC-135-mediated resistance to ceftazidime-avibactam in ST11-K47 hypervirulent Klebsiella pneumoniae.

Ceftazidime-avibactam resistance attributable to the blaKPC-2 gene mutation is increasingly documented in clinical settings. In this study, we characterized the mechanisms leading to the development of ceftazidime-avibactam resistance in ST11-K47 hypervirulent Klebsiella pneumoniae that harboured the blaKPC-135 gene. This strain possessed fimbriae and biofilm, demonstrating pathogenicity. Compared with the wild-type KPC-2 carbapenemase, the novel KPC-135 enzyme exhibited a deletion of Glu168 and Leu169 and a 15-amino acid tandem repeat between Val262 and Ala276. The blaKPC-135 gene was located within the Tn6296 transposon truncated by IS26 and carried on an IncFII/IncR-type plasmid. Compared to the blaKPC-2-positive cloned strain, only the MIC of ceftazidime increased against blaKPC-135-positive K. pneumoniae and wasn't inhibited by avibactam (MIC 32 µg/mL), while clavulanic acid and vaborbactam demonstrated some inhibition. Kinetic parameters revealed that KPC-135 exhibited a lower Km and kcat/Km with ceftazidime and carbapenems, and a higher (∼26-fold) 50% inhibitory concentration with avibactam compared to KPC-2. The KPC-135 enzyme exerted a detrimental effect on fitness relative to the wild-type strain. Furthermore, this strain possessed hypervirulent determinants, which included the IncHI1B/FIB plasmid with rmpA2 and expression of type 1 and 3 fimbriae. In conclusion, we reported a novel KPC variant, KPC-135, in a clinical ST11-K47 hypervirulent K. pneumoniae strain, which conferred ceftazidime-avibactam resistance, possibly through increased ceftazidime affinity and decreased avibactam susceptibility. This strain simultaneously harboured resistance and virulence genes, posing an elevated challenge in clinical treatment.

Outbreak of OXA-232-producing carbapenem-resistant Klebsiella pneumoniae ST15 in a Chinese teaching hospital: a molecular epidemiological study.

Background and Aims: The incidence of OXA-232-producing carbapenem-resistant Klebsiella pneumoniae (CRKP) has been on the rise in China over the past five years, potentially leading to nosocomial epidemics. This study investigates the first outbreak of CRKP in the Second Affiliated Hospital of Jiaxing University. Methods: Between February 2021 and March 2022, 21 clinical isolates of OXA-232-producing CRKP were recovered from 16 patients in the Second Affiliated Hospital of Jiaxing University. We conducted antimicrobial susceptibility tests, whole genome sequencing, and bioinformatics to determine the drug resistance profile of these clinical isolates. Results: Whole-genome sequencing revealed that all 21 OXA-232-producing CRKP strains belonged to the sequence type 15 (ST15) and shared similar resistance, virulence genes, and plasmid types, suggesting clonal transmission between the environment and patients. Integrated genomic and epidemiological analysis traced the outbreak to two clonal transmission clusters, cluster 1 and cluster 2, including 14 and 2 patients. It was speculated that the CRKP transmission mainly occurred in the ICU, followed by brain surgery, neurosurgery, and rehabilitation department. Phylogenetic analysis indicated that the earliest outbreak might have started at least a year before the admission of the index patient, and these strains were closely related to those previously isolated from two major adjacent cities, Shanghai and Hangzhou. Comparative genomics showed that the IncFII-type and IncHI1B-type plasmids of cluster 2 had homologous recombination at the insertion sequence sites compared with the same type of plasmids in cluster 1, resulting in the insertion of 4 new drug resistance genes, including TEM-1, APH(6)-Id, APH(3'')-Ib and sul2. Conclusions: Our study observed the clonal spread of ST15 OXA-232-producing between patients and the hospital environment. The integration of genomic and epidemiological data offers valuable insights and facilitate the control of nosocomial transmission.

Relationship between antibiotic exposure and carbapenem-resistant Klebsiella pneumoniae infection within four types of control patients: A systematic review and meta-analysis.

OBJECTIVES: This study attempted to identify the relationship between antibiotic exposure and risk of carbapenem-resistant Klebsiella pneumoniae (CRKP) infection. METHODS: Antibiotic exposure was analysed as a risk factor for CRKP infection, cases of which were extracted from research articles indexed in PubMed, EMBASE, and the Cochrane Library. Relevant studies published until January 2023 were reviewed, and a meta-analysis was conducted on antibiotic exposure within four types of control groups, which comprised 52 studies. RESULTS: The four types of control groups included carbapenem-susceptible K. pneumoniae infections (CSKP; comparison 1); other infections, especially without CRKP infection (comparison 2); CRKP colonisation (comparison 3); and no infection (comparison 4). Carbapenems exposure and Aminoglycosides exposure were two risk factors common to the four comparison groups. Compared with the risk of CSKP infection, tigecycline exposure in bloodstream infections and quinolone exposure within 30 days were associated with an increased risk of CRKP infection. However, the risk of CRKP infection associated with tigecycline exposure in mixed (MIX) infections (infections involving two or more different infection sites) and quinolone exposure within 90 days was similar to the risk of CSKP infection. CONCLUSION: Carbapenems and Aminoglycosides exposure are likely risk factors for CRKP infection. Antibiotic exposure time as a continuous variable was not associated with the risk of CRKP infection, compared with the risk of CSKP infection. Tigecycline exposure in MIX infections and quinolone exposure within 90 days may not increase the risk of CRKP infection.

Evaluation of polymyxin B AUC/MIC ratio for dose optimization in patients with carbapenem-resistant Klebsiella pneumoniae infection.

Polymyxin B has been used as a last-line therapy for the treatment of carbapenem-resistant gram-negative bacterial infection. The pharmacokinetic/pharmacodynamic index (AUC/MIC) of polymyxin B has not been clinically evaluated, given that the broth microdilution method for polymyxin susceptibility testing is rarely used in hospitals. This study analyzed data from 77 patients with carbapenem-resistant Klebsiella pneumoniae infections. Among the samples, 63 K. pneumoniae isolates had MIC values of 1.0 mg/L as measured by broth microdilution but 0.5 mg/L as measured using the Vitek 2 system. Polymyxin B AUC/MIC was significantly associated with clinical response (p = 0.002) but not with 30-day all-cause mortality (p = 0.054). With a target AUC/MIC value of 50, Monte Carlo simulations showed that a fixed dose of 100 mg/12 h and three weight-based regimens (1.25 mg/kg/12 h for 80 kg and 1.5 mg/kg/12 h for 70 kg/80 kg) achieved a cumulative fraction of response >90% regardless of renal function, but the risk of nephrotoxicity was high. For patients with carbapenem-resistant K. pneumoniae infections, the underestimation of polymyxin resistance in automated systems need to be taken into account when optimizing polymyxin B dosing based on pharmacokinetic/pharmacodynamic principles.

Risk Factors for Mortality and Outcomes in Hematological Malignancy Patients with Carbapenem-Resistant Klebsiella pneumoniae Bloodstream Infections.

Background: This study aimed to identify risk factors for mortality and outcomes in hematological malignancy (HM) patients with bloodstream infection (BSI) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). Methods: A retrospective study was conducted at a tertiary teaching hospital in Henan Province, China, between January 2018 and December 2021. All BSIs caused by CRKP in hospitalized HM patients were identified. Data on patient demographics, disease, laboratory tests, treatment regimens, outcomes of infection, and the antimicrobial susceptibility of each isolate were collected from medical records. Results: A total of 129 patients with CRKP BSI were included in the study, and the 28-day mortality rate was 80.6% (104/129). In Cox analysis an absolute neutrophil count < 500 at discharge (hazard ratio [HR] 6.386, 95% confidence interval [CI] 3.074-13.266, p < 0.001), intensive care unit admission (HR 1.834, 95% CI 1.065-3.157, p = 0.029), and higher Pitt bacteremia score (HR 1.185, 95% CI 1.118-1.255, p < 0.001) were independent risk factors associated with 28-day mortality. Survival curve analysis indicated that compared with ceftazidime-avibactam-based therapy, both polymyxin b (HR 8.175, 95% CI 1.099-60.804, p = 0.040) and tigecycline (HR 14.527, 95% CI 2.000-105.541, p =0.008) were associated with a higher risk of mortality. Conclusion: In HM patients CRKP BSI resulted in high mortality. Intensive care unit admission, higher Pitt bacteremia score, and absolute neutrophil count < 500 at discharge were independently associated with higher mortality. Early initiation of new agents such as ceftazidime-avibactam may improve outcomes.

Disease burden and molecular epidemiology of carbapenem-resistant Klebsiella pneumonia infection in a tertiary hospital in China.

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKP) has become an urgent global public health issue, but its distribution has obvious regional differences. The purpose of this study was to investigate the patient-based disease burden and molecular epidemiology of CRKP infections in a tertiary hospital in northern Jiangsu Province in China. METHODS: A retrospective, epidemiological survey of CRKP infections in our hospital from January to December 2016 was conducted to collect clinical and epidemiologic data. Non-duplicated clinical CRKP isolates were collected for the resistance-associated genes and clonal correlation analysis by PCR, sequencing and multilocus sequence typing (MLST). RESULTS: 252 CRKP infection cases were collected, and the annual CRKP infection incidence of the hospital during 2016 was 14.64 per 10,000 hospital discharges (252/172,112*10,000) and 13.78 per 100,000 patient days (252/1,829,190*100,000). The patient-based disease burden concentrated on antimicrobial exposure history (133/224, 59.37%)-the most dominant STs. KPC-2 (120/128, 93.8%) was the predominant carbapenemase and ST11 (98/128, 76.5%) was the dominant STs. One isolate was detected with harboring bla KPC-2 and bla MCR-1 simultaneously. CONCLUSIONS: Patient-based disease burden and KPC-2-producing ST11 Klebsiella pneumonia caused in higher CRKP incidence in the hospital. The emergence of CRKP with bla KPC-2 and bla MCR-1 should be of concern.

Epidemiology and Risk Factors for Carbapenem-Resistant Klebsiella Pneumoniae and Subsequent MALDI-TOF MS as a Tool to Cluster KPC-2-Producing Klebsiella Pneumoniae, a Retrospective Study.

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) appeared recently and now presents a particularly critical problem to hospitalized patients worldwide. We aim to investigate the epidemiology and the risk factors for CRKP colonization and infections, and to evaluate the application performance of MALDI-TOF MS in clustering CRKP. Results: CRKP colonization and infections incidence was 2.7 (35/1,319,427) per 100,000 patient-days. Inpatients in CRKP group had higher medical expense than CSKP group. Inpatients with underlying conditions, particularly with pulmonary diseases, and with antimicrobial use prior to culture within 30 days, especially with carbapenem use, were risk factors for CRKP acquisition. All CRKP isolates were detected producing KPC-2. The MALDI-TOF MS system and PFGE system provided similar results, with a good concordance between the two methods (adjusted Rand's coefficient, 0.846) and a high probability of MALDI-TOF MS to predict PFGE results (Wallace coefficient, 0.908). Conclusions: Underlying conditions, particularly pulmonary diseases, and antimicrobial use prior to culture within 30 days, especially carbapenem use, are risk factors for CRKP acquisition. BlaKPC-2 is the mainstream gene of CRKP in our geographic area of analysis. As only simple sample preparation is needed and the results can be obtained in a short time, MALDI-TOF MS may be considered a probable alternative to PFGE in clustering KPC-2-producing CRKP.

Carbapenem-resistant Klebsiella pneumoniae in ICU-admitted COVID-19 patients: Keep an eye on the ball.

Here we report on seven intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS) who developed positive rectal swabs and invasive infections due to carbapenemase-producing Klebsiella pneumoniae (CP-Kp). Notwithstanding the infection prevention measures introduced during the COVID-19 pandemic and changes in the hospitalised population, attention to CP-Kp infections must remain high, especially in the critically ill setting.

The Nomogram model was established for the risk assessment of intestinal colonization with neonatal CRKP / 实用医学杂志

Objective To establish a Nomogram model for assessing the risk of intestinal colonization by Carbapenem-Resistant Klebsiella pneumoniae(CRKP)to determine the specific probability of colonization and adopt individualized prevention strategies for the purpose of reducing the occurrence of colonization and secondary infection of neonatal CRKP.Methods A total of 187 neonates hospitalized between January 2021 and October 2022 and diagnosed with CRKP colonization by rectal swab/fecal culture as well drug sensitivity identification 48 h after admission were assigned to the CRKP group.Another 187 neonates without non-CRKP colonization during the same period were set as the non-CRKP group.All the data of the two groups were used for a retrospective analysis.The caret package in R 4.2.1 was used to randomly divide the 374 cases into the model group and validation group at a ratio of 3∶1.Then the glmnet package in R 4.2.1 was used to conduct a LASSO regression analysis over the data from the model group to determine the predictive factors for modeling and the rms software package was used to build a Nomogram model.The pROC and rms packages in R 4.2.1 were used to examine the data,analyzing the consistency indexes(Cindex),receiver operating characteristic curves(ROC),and area under the curves(AUC)and performing the internal and external validation of the efficacy of the Nomogram model via the calibration curves.Results LASSO regression analysis determined eight predictors from the 35 factors probably affecting neonatal CRKP colonization:gender,cesarean section,breastfeeding,nasogastric tube,enema,carbapenems,probiotics,and hospital stay.The Nomogram model constructed using these eight predictors as variables could predict CRKP colonization to a moderate extent,with the area under the ROC curve of 0.835 and 0.800 in the model and validation group,respectively.The Hos-mer-Lemeshow test showed that the predicted probability was highly consistent with the actual probability(the modeling group:P = 0.678>0.05;the validation group:P = 0.208>0.05),presenting a higher degree of fitting.Conclusion The Nomogram model containing such variables as gender,cesarean section,breastfeeding,nasogastric tube,enema,carbapenems,probiotics,and hospital stay is more effective in predicting the risk of neonatal CRKP colonization.Therefore,preventive measures should be individualized based on the colonization probability predicted by the Nomogram model in order to keep neonates from CRKP colonization and reduce the incidence of secondary CRKP infections among them.

Prospective investigation of carbapenem-resistant Klebsiella pneumonia transmission among the staff, environment and patients in five major intensive care units, Beijing.

BACKGROUND: Following the alarming outbreak of carbapenem-resistant Klebsiella pneumonia (CRKP) in five intensive care units (ICUs) of a tertiary care hospital in China, a prospective investigation of CRKP colonized/infected patients was conducted. AIM: To describe the diffusion and transmission of CRKP among epidemiologically linked ICU patients, staff and environment. METHODS: Enhanced CRKP infected/colonized case monitoring was performed by the real-time nosocomial infection surveillance system (RT-NISS). The immediate surroundings of each CRKP patient bed unit and the staff hands/gloves/gowns were sampled and then evaluated for the presence of CRKP. Antimicrobial susceptibility tests, pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing (WGS) were used to identify and to characterize these isolates. FINDINGS: Among 2750 patients monitored, 67 CRKP patients were newly labeled and 11 patients' CRKP isolates were available. A total of 31.34% (21/67) bed units were positive at one or more surrounding surfaces, 7.99% (49/613) environmental samples and 3.57% (4/112) ICU staff samples were CRKP positive. The selected CRKP isolates (N = 64) exhibited intermediate to high resistance levels to the antibiotics tested apart from colistin and tigecycline. RT-NISS data combined with MLST and PFGE revealed nine likely transmission clusters. WGS analysis of these CRKP isolates revealed extensive sharing of multiple antimicrobial resistance genes and plasmid replicons among these isolates. Two carbapenemase genes blaKPC-2 (62/64) and blaOXA-48 (2/64) were identified. These CRKP isolates carried one or more plasmid replicons. CONCLUSIONS: The contamination of ICU environment and staff's hands, gloves or gowns is frequent with CRKP patients. Our study also supports the hypothesis that an association between environmental contamination and transmission of CRKP bacteria in ICUs.

Clinical and molecular epidemiologic characteristics of carbapenem-resistant Klebsiella pneumoniae infection/colonization among neonates in China.

BACKGROUND: The spread of carbapenem-resistant Klebsiella pneumoniae (CR-KPN) is a major concern, but data on CR-KPN infection/colonization in paediatric populations are limited. AIM: To analyse epidemiologic and clinical characteristics, and therapeutic options for CR-KPN infections in neonates in China. METHODS: A retrospective study was performed at the Children's Hospital of Fudan University, including 88 neonates with CR-KPN admitted between November 2015 and October 2016. Forty-seven CR-KPN isolates were chosen at random for further study, including antimicrobial susceptibility testing, potential ß-lactamase screening and homology analysis. FINDINGS: In total, 44.3% (39/88) of the neonates with CR-KPN were infected, and 71.8% (28/39) were nosocomial infections. Of these, pneumonia and urinary tract infection accounted for 50.0% (14/28) and 42.9% (12/28), respectively. All infected patients were cured or improved with fosfomycin and/or carbapenem-containing combination therapy, except one case in whom treatment was withdrawn. All 47 cases of CR-KPN were resistant to ertapenem and 95.7% were resistant to imipenem/meropenem. Overall, 87.2% (41/47) were positive for blaNDM-1, and belonged to 11 pulsed-field gel electrophoresis types; 53.7% (22/41) were designated as ST278 and 17.1% (7/41) were designated as ST2735 by multi-locus sequence typing. CONCLUSIONS: Most of the CR-KPN isolated from neonates produced New Delhi metallo-beta-lactamase-1 and were highly homologous. Fosfomycin-containing regimens and meropenem-/panipenem-containing combination therapy were efficient for CR-KPN infection in neonates.

Investigation of a suspected outbreak of carbapenem-resistant Klebsiella pneumonia infection / 上海预防医学

ObjectiveTo investigate a suspected outbreak of healthcare-associated infection （HAI） caused by carbapenem-resistant Klebsiella pneumonia （CRKP） in a secondary grade-A hospital， analyze the infection source and transmission route， and put forward corresponding preventive and control measures. MethodsEpidemiological investigation was conducted on 5 patients with CRKP infection in department of neurosurgery during December 23‒30， 2021. Specimens were collected with the environmental microbiology monitoring procedure. CRKP isolated from the environmental samples were analyzed by multilocus sequence typing （MLST） method. Comprehensive measures were taken to control the CRKP infection. ResultsThe 5 infected patients were located in 3 rooms， and all were diagnosed as HAI. The antimicrobial susceptibility testing results from the specimens of 3 CRKP infected patients were the same. Through environmental microbiology monitoring， CRKP strains were detected from the faucet handle and sink specimens in 3 rooms. The results of MLST analysis showed that the faucet handle and sink specimens in room 2 and 3 were ST11 type. The environmental specimen in room 1 was ST23 type. The suspected outbreak was effectively controlled after comprehensive interventions. ConclusionHAI suspected outbreak might be caused by the environmental contamination from the pathogens of CRKP-infected patients as well as the contaminated hands of medical staff and accompanying family members. Strengthening the publicity， education and management of medical staff and accompanying staff， early identification of infection outbreaks， and timely comprehensive control measures are the keys to controlling multidrug-resistant nosocomial infection outbreaks.

Retrospective analysis of fosfomycin combinational therapy for sepsis caused by carbapenem-resistant Klebsiella pneumoniae.

The aim of the present study was to compare the efficacy and safety of fosfomycin combinational therapy with other antibiotics for the treatment of infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). This retrospective cohort study examined 104 cases of sepsis caused by CRKP occurring between January 2012 and November 2014 in Shanghai Tenth People's Hospital. Three categories of patient outcome were assessed: Survival/mortality, duration of intensive care unit stays and duration of medical ventilation. Univariate ordinal analyses were adopted to evaluate the correlations between outcome and treatment. A total of 104 patients with physician-diagnosed CRKP were involved in the study. The overall mortality rate was 25.0%. The majority of the infections (84; 80.8%) were hospital acquired. Critical infections received more than one active antibiotic as therapy. Patients treated with fosfomycin combinational therapy were less likely to fail therapy (OR: 4.71, 95% CI: 1.03-21.65, P=0.034) and tended to have a shorter duration of mechanical ventilation. Gender (OR: 4.35, 95% CI: 1.08-3.60, P=0.037), history of chronic obstructive pulmonary disease (OR: 9.35, 95% CI: 0.06-0.19, P=0.007) and peripheral catheter use (OR: 3.00, 95% CI: 0.07-0.19, P=0.002) are risk factors for clinical outcome. Therefore, the use of fosfomycin combinational therapy for treatment of infection due to CRKP appears to be associated with improved survival rate.

Severe COVID-19-associated sepsis is different from classical sepsis induced by pulmonary infection with carbapenem-resistant klebsiella pneumonia (CrKP) / 中华创伤杂志(英文版)

PURPOSE@#COVID-19 is also referred to as a typical viral septic pulmonary infection by 2019-nCoV. However, little is known regarding its characteristics in terms of systemic inflammation and organ injury, especially compared with classical bacterial sepsis. This article aims to investigate the clinical characteristics and prognosis between COVID-19-associated sepsis and classic bacterial-induced sepsis.@*METHODS@#In this retrospective cohort study, septic patients with COVID-19 in the intensive care unit (ICU) of a government-designed therapy center in Shenzhen, China between January 14, 2020 and March 10, 2020, and septic patients induced by carbapenem-resistant klebsiella pneumonia (CrKP) admitted to the ICU of the Second People's Hospital of Shenzhen, China between January 1, 2014 and October 30, 2019 were enrolled. Demographic and clinical parameters including comorbidities, critical illness scores, treatment, and laboratory data, as well as prognosis were compared between the two groups. Risk factors for mortality and survival rate were analyzed using multivariable logistic regression and survival curve, respectively.@*RESULTS@#A total of 107 patients with COVID-19 and 63 patients with CrKP were enrolled. A direct comparison between the two groups demonstrated more serious degrees of primary lung injury following 2019-nCoV infection (indicated by lower PaO@*CONCLUSION@#Critical COVID-19 shares clinical characteristics with classical bacterial sepsis, but the degree of systemic inflammatory response, secondary organ damage and mortality rate are less severe. However, following 2019-nCoV infection, the level of immunosuppression may be increased and thus induce in more death at the later stage of patients' hospitalstay.