Molecular characterization of NDM and OXA-48-like-producing Klebsiella pneumoniae ST16 and hypervirulent ST337 clone among two patients; a case report.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are a major public health problem, requiring the use of last-resort antibiotics such as colistin. However, there is concern regarding the emergence of isolates resistant to this agent. The report describes two patients with urinary tract infection (UTI) and ventilator-associated pneumonia (VAP) infection caused by CRKP strains. The first case was a 23-year-old male with UTI caused by a strain of ST16 co-harboring blaCTX-M, blaTEM, blaSHV, blaNDM, blaOXA-48-like genes. The second case was a 39-year-old woman with VAP due to hypervirulent ST337-K2 co-harboring blaSHV, blaNDM, blaOXA-48-like, iucA, rmpA2 and rmpA. The patients' general condition improved after combination therapy with colistin (plus meropenem and rifampin, respectively) and both of them recovered and were discharged from the hospital. This study highlights the necessary prevention and control steps to prevent the further spread of CRKP strains should be a priority in our hospital.

Antibiotics Removal during Continuous Renal Replacement Therapy in Septic Shock Patients: Mixed Modality Versus "Expanded Haemodialysis".

BACKGROUND AND OBJECTIVE: Renal replacement therapy (RRT) plays a critical role in antimicrobial removal, particularly for low-molecular-weight drugs with low plasma protein binding, low distribution volume and hydrophilicity. Medium cut-off (MCO) membranes represent a new generation in dialysis technology, enhancing diffusive modality efficacy and increasing the cut-off from 30 to 45 kDa, crucial for middle molecule removal. This monocentric randomized crossover pilot study aimed to evaluate the impact of continuous haemodialysis with MCO membrane (MCO-CVVHD) on the removal of piperacillin, tazobactam and meropenem compared with continuous veno-venous hemodiafiltration with standard high-flux membrane (HFM-CVVHDF). METHODS: Twenty patients were randomized to undergo MCO-CVVHD followed by HFM-CVVHDF or vice versa. Extraction ratio (ER), effluent clearance (Cleff) and treatment efficiency were assessed at various intervals. Antibiotic nadir plasma levels were measured for both treatment days. RESULTS: HFM-CVVHDF showed greater ER compared with MCO-CVVHD for meropenem (ß = - 8.90 (95% CI - 12.9 to - 4.87), p < 0.001) and tazobactam (ß = - 8.29 (95% CI - 13.5 to - 3.08), p = 0.002) and Cleff for each antibiotic (meropenem ß = - 10,206 (95% CI - 14,787 to - 5787), p = 0.001); tazobactam (ß = - 4551 (95% CI - 7781 to - 1322), p = 0.012); piperacillin (ß = - 3913 (95% CI - 6388 to - 1437), p = 0.002), even if the carryover effect influenced the Cleff for meropenem and tazobactam. No difference was observed in nadir plasma concentrations or efficiency for any antibiotic. Piperacillin (ß = - 38.1 (95% CI - 47.9 to - 28.3), p < 0.001) and tazobactam (ß = - 4.45 (95% CI - 6.17 to - 2.72), p < 0.001) showed lower nadir plasma concentrations the second day compared with the first day, regardless the filter type. CONCLUSION: MCO demonstrated comparable in vivo removal of piperacillin, tazobactam and meropenem to HFM.

Splenic abscess secondary to COVID-19 acute infection: A case report and literature review.

RATIONALE: Splenic abscess is relatively rare in clinical practice as an invasive disease. However, during the continuous prevalence of coronavirus disease 2019 (COVID-19), the incidence rate of splenic abscess showed an upward trend. However, because the etiology of splenic abscess is not specific, it is easy to be covered by the respiratory symptoms of COVID-19, resulting in omission or delay in diagnosis. If splenic abscesses cannot be treated in a timely manner, the mortality rate can reach 100%. Therefore, it is important to fully understand the correlation between COVID-19 and the development of splenic abscesses. PATIENT CONCERNS: A female patient, 71 years of age, was admitted to our hospital because of cough and sputum for 1 week and fever for 2 days. According to the positive results of novel coronavirus nucleic acid and chest computed tomography, novel coronavirus pneumonia was diagnosed. On the 4th day after treatment, abdominal distension and vomiting were observed. Abdominal ultrasound indicated splenomegaly and mixed echo masses in the spleen and abdominal computed tomography indicated 2 new round low-density lesions were found in the spleen. DIAGNOSES: The patient was diagnosed with secondary splenic abscess after COVID-19 infection. INTERVENTIONS: The patient and her family members refused to undergo ultrasound-guided splenic puncture drainage and splenectomy. In terms of treatment, she was given meropenem combined with vancomycin to continue anti-infection treatment. OUTCOMES: The patient's body temperature and infection indicators gradually increased, and the scope of splenic abscess continued to expand. The infection worsened and progressed to septic shock. The patient abandoned rescue drugs and invasive treatment, and died on the 9th day after admission. LESSONS: This case introduces the clinical characteristics of secondary splenic abscess caused by COVID-19 from the aspects of etiology, disease course, clinical manifestations, auxiliary examinations, and treatment methods. The focus is on improving the understanding of clinical doctors about secondary splenic abscesses caused by COVID-19, providing reference for early diagnosis and timely treatment.

An investigation of broad-spectrum antibiotic-induced liver injury based on the FDA Adverse Event Reporting System and retrospective observational study.

Tazobactam/piperacillin and meropenem are commonly used as an empiric treatment in patients with severe bacterial infections. However, few studies have investigated the cause of tazobactam/piperacillin- or meropenem-induced liver injury in them. Our objective was to evaluate the association between tazobactam/piperacillin or meropenem and liver injury in the intensive care unit patients. We evaluated the expression profiles of antibiotics-induced liver injury using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. Further, in the retrospective observational study, data of patients who initiated tazobactam/piperacillin or meropenem in the intensive care unit were extracted. In FAERS database, male, age, the fourth-generation cephalosporin, carbapenem, ß-lactam and ß-lactamase inhibitor combination, and complication of sepsis were associated with liver injury (p < 0.001). In the retrospective observational study, multivariate logistic regression analyses indicated that the risk factors for liver injury included male (p = 0.046), administration period ≥ 7 days (p < 0.001), and alanine aminotransferase (p = 0.031). Not only administration period but also sex and alanine aminotransferase should be considered when clinicians conduct the monitoring of liver function in the patients receiving tazobactam/piperacillin or meropenem.

Evolution of blaKPC Under the Pressure of Carbapenems and Ceftazidime/Avibactam in a Patient With Persistent Bacteremia Caused by Klebsiella pneumoniae.

A 30-year-old Korean man with myelodysplastic syndrome admitted hospital due to undifferentiated fever and recurrent skin lesions. He received combination therapy with high doses of meropenem, tigecycline and amikacin, yielding carbapenem resistant Klebsiella pneumoniae (CRKP) harboring K. pneumoniae carbapenemase (KPC)-2 from blood cultures on hospital day (HD) 23. Ceftazidime/avibactam was started at HD 37 and CRKP was eradicated from blood cultures after 5 days. However, ceftazidime/avibactam-resistant CRKP carrying KPC-44 emerged after 26 days of ceftazidime/avibactam treatment and then ceftazidime/avibactam-resistant, carbapenem-susceptible K. pneumoniae carrying KPC-135 was isolated on HD 65. The 3-D homology of KPC protein showed that hot spot changes in the omega loop could be attributed to ceftazidime/avibactam resistance and loss of carbapenem resistance. Whole genome sequencing of serial isolates supported that phenotypic variation was due to clonal evolution than clonal replacement. The treatment regimen was changed from CAZ/AVI to meropenem-based therapy (meropenem 1 g iv q 8 hours and amikacin 600 mg iv per day) starting with HD 72. CAZ/AVI-susceptible CRKP was presented again from blood cultures on HD 84, and the patient expired on HD 85. This is the first Korean report on the acquisition of ceftazidime/avibactam resistance through the emergence of blaKPC variants.

Bacterascites caused by Salmonella spp. following a cesarean section: A case report.

RATIONALE: Bacterascites are a rare complication of cesarean sections (C/S). Here, we report the case of a patient with bacterascites after an emergent C/S. PATIENT CONCERN: A 41-year-old female reported diffuse abdominal tightness and pain for a week after C/S, who received C/S at 38 4/7 weeks due to superimposed preeclampsia and prolonged labor. DIAGNOSES: Bacterascites caused by Salmonella species after C/S was diagnosed. INTERVENTIONS: Initial treatment included cefmetazole and metronidazole. On day 2, paracentesis was performed, followed by albumin and hydroxyethyl starch administration. By day 3, the patient developed pulmonary edema, necessitating Lasix administration. On day 6, ascites culture revealed Salmonella species resistant to third-generation cephalosporins, leading to meropenem therapy adjustment. This resulted in improved symptoms. Meropenem was continued for 14 days to complete the treatment regimen. OUTCOMES: Follow-up ultrasonography revealed a decrease in ascites. As the patient clinical condition improved, she was discharged on day 20 and scheduled for outpatient department follow-up. No recurrence of ascites was observed during the subsequent follow-up period of 3 months. No ascites were noted 8 days after discharge. LESSONS: Postoperative bacterascites with Salmonella were diagnosed. Antibiotic treatment and therapeutic paracentesis were effective for this condition.

A SEVERE CASE OF NON TYPHOIDAL SALMONELLA ASSOCIATED WITH MULTIPLE ORGAN DAMAGE- CASE STUDY AND LITERATURE REVIEW.

We report a severe case of a 25-year-old girl presented with complaints of weakness, diarrhoea, vomiting, pain in abdomen and hypotension at Infectious Diseases and Clinical Immunology Research Center. From history on 25 February till 29 February she was in India and on 1 march this problem started with watery diarrhoea followed by vomiting. She ate pizza with mushroom following which her condition worsened. Stool culture revealed salmonella nontyphi (nonthyphodal Salmonella)and this is leading cause for gastroenteritis, bacteremia and affects several other bodily system. Her condition deteriorated due to the development of ARDS (acute respiratory distress syndrome) and for this she was on mechanical ventilation. Vitec machine was performed, which identified Salmonella typhi murium. Our goal is to manage and treat this patient well by early diagnosis. She was given ceftriaxone, iv fluids and symptomatic treatment but due to resistance meropenem was started and the patient's condition improved. From serology there was no evidence of immunocompromised state so being a severe case of immunocompetent patient this case reflects the importance of timely diagnosis and management together with food safety practices in population. On follow up she was stable and discharged after 3 weeks. Future research studies need to be continued regarding newer strains, effective treatment strategies and diagnostics to prevent morbidity and mortality.

Butyricimonas faecihominis: an atypically resistant bacterium implicated in abscess formation - a case report.

BACKGROUND: This case report presents a unique instance of abscesses with an uncommon pathogen isolated from blood cultures. CASE PRESENTATION: We present the case of a perianal abscess in a 50-year-old man with a history of cocaine abuse and bilateral hip replacements. The rapid progression led to septic shock and multi-organ failure, requiring intensive care unit admission, surgery including protective transversostomy. Blood cultures showed growth of Butyricimonas spp. with resistance to penicillin and piperacillin-tazobactam. The immediate switch to meropenem led to a significant improvement in the patient's condition. The patient was discharged after 40 days of hospitalization in good general condition and the reversal of the transversostomy was performed six months later. CONCLUSION: The identification of Butyricimonas faecihominis, a rarely reported pathogen, emphasizes the challenges of diagnosing and treating unusual infections. This case emphasizes the importance of rapid microbiological diagnosis, interdisciplinary collaboration, and targeted antibiotic therapy in the treatment of abscesses and sepsis.

Sepsis caused by Phytobacter diazotrophicus complicated with galactosemia type 1 in China: a case report.

BACKGROUND: Phytobacter diazotrophicus (P. diazotrophicus) is an opportunistic pathogen that causes nosocomial outbreaks and sepsis. However, there are no reports of P. diazotrophicus isolated from human blood in China. CASE PRESENTATION: A 27-day-old female infant was admitted to our hospital with fever and high bilirubin levels. The clinical features included jaundice, abnormal coagulation, cholestasis, fever, convulsions, weak muscle tension, sucking weakness, ascites, abnormal tyrosine metabolism, cerebral oedema, abnormal liver function, clavicle fracture, and haemolytic anaemia. The strain isolated from the patient's blood was identified as P. diazotrophicus by whole-genome sequencing (WGS). Galactosemia type 1 (GALAC1) was diagnosed using whole-exome sequencing (WES). Based on drug sensitivity results, 10 days of anti-infective treatment with meropenem combined with lactose-free milk powder improved symptoms. CONCLUSION: P. diazotrophicus was successfully identified in a patient with neonatal sepsis combined with galactosemia. Galactosemia may be an important factor in neonatal sepsis. This case further expands our understanding of the clinical characteristics of GALAC1.

Usage of Meropenem Continuous Infusion for Treatment of Infectious Complications in Orthopedic Elderly Patients with Anemia: A Case Series.

Background and Objectives: The prolonged infusion of meropenem is recommended by guidelines for the treatment of sepsis. However, studies provide controversial data on the advantages of prolonged infusions over intermittent ones. In our opinion, this can be related to age, which possibly distorts the final data, as older people have age-related characteristics. In our study, we analyzed the ventilatory status, laboratory tests and vital signs of the patient and carried out microbiological cultures. Materials and Methods: This was a prospective single-center case series investigation conducted from June 2022 to June 2023. The objective of this study was to evaluate the effectiveness of continuous infusion in elderly patients with severe infectious complications after orthopedic interventions. The primary endpoints were 28-day survival and the emergence of new multidrug-resistant strains. Secondary endpoints were long-term mortality and length of stay in the ICU. Results: Three patients (median age 65, 100% female) received a continuous infusion of meropenem. Two patients were alive at hospital discharge, and one patient died on the 105th day of hospitalization. Multi-resistant bacteria were observed in one patient. Conclusions: The use of a continuous meropenem infusion in the complex treatment of purulent-septic complications in elderly patients with periprosthetic infection and anemia probably led to clinical improvement in these case reports. However, the emergence of new pan-resistant strains and overall mortality using this infusion technique remains unclear. Further, high-quality RCTs for the elderly are needed.

In complicated UTIs, cefepime-taniborbactam increased treatment success vs. meropenem at 19 to 23 d.

SOURCE CITATION: Wagenlehner FM, Gasink LB, McGovern PC, et al; CERTAIN-1 Study Team. Cefepime-taniborbactam in complicated urinary tract infection. N Engl J Med. 2024;390:611-622. 38354140.

Clinical outcomes in patients infected with ertapenem-only-resistant Enterobacterales versus multi-carbapenem-resistant Enterobacterales.

BACKGROUND: Use of anti-carbapenem-resistant Enterobacterales (anti-CRE) agents such as ceftazidime/avibactam has been associated with improved clinical outcome in cohorts that primarily include patients infected with CRE that are resistant to meropenem (MCRE). OBJECTIVES: To clarify whether patients with CRE resistant to ertapenem but susceptible to meropenem (ertapenem-only-resistant Enterobacterales; EORE) benefit from therapy with anti-CRE agents. METHODS: Patients treated for CRE infection in hospitals in the USA between 2016 and 2019 and enrolled in the CRACKLE-2 study were included. The primary outcome was the desirability of outcome ranking (DOOR) assessed at 30 days after index cultures. RESULTS: The EORE group included 213 patients and the MCRE group included 643. The demographics were similar between the groups except for the patients' race and origin before admission. The MCRE group received anti-CRE agents for definitive therapy significantly more frequently compared with the EORE group (30% versus 5% for ceftazidime/avibactam). We did not observe a significant difference between the groups in the adjusted DOOR probability of a more desirable outcome for a randomly selected patient in the EORE group compared with the MCRE group (52.5%; 95% CI, 48.3%-56.7%). The MCRE group had a similar proportion of patients who died at 30 days (26% versus 21%) and who were discharged to home (29% versus 40%), compared with the EORE group. CONCLUSIONS: Patients with clinical EORE infection rarely received anti-CRE agents, but attained similar outcomes compared with patients with MCRE infection. The findings support current IDSA treatment guidance for meropenem- or imipenem-based therapy for treatment of EORE infections.

Patient outcomes by baseline pathogen resistance phenotype and genotype in CERTAIN-1, a Phase 3 study of cefepime-taniborbactam versus meropenem in adults with complicated urinary tract infection.

CERTAIN-1 was a Phase 3, double-blind, randomized, parallel group study of the efficacy and safety of cefepime-taniborbactam versus meropenem in the treatment of adults with complicated urinary tract infection (cUTI), including acute pyelonephritis. We determined susceptibility of Enterobacterales and Pseudomonas aeruginosa baseline pathogens to cefepime-taniborbactam and comparators and characterized ß-lactam resistance mechanisms. Microbiologic response and clinical response were assessed in patient subsets defined by baseline pathogens that were of cefepime-, multidrug-, or carbapenem-resistant phenotype or that carried ß-lactamase genes. Among Enterobacterales baseline pathogens, 26.8%, 4.1%, and 3.0% carried genes for extended-spectrum ß-lactamases (ESBLs), AmpC, and carbapenemases, respectively. Within each treatment group, while composite success rates at Test of Cure in resistant subsets by pathogen species were similar to those by pathogen overall, composite success rates in meropenem patients were numerically lower for cefepime-resistant Escherichia coli (9/19; 47.4%) and ESBL E. coli (13/25; 52.0%) compared with E. coli overall (62/100; 62.0%). Cefepime-taniborbactam achieved composite success in 7/8 (87.5%) patients with carbapenem-resistant Enterobacterales and 8/9 (88.9%) patients with Enterobacterales with a carbapenemase gene (5 OXA-48-group; 2 KPC-3; 2 NDM-1). Cefepime-taniborbactam also achieved composite success in 8/16 (50.0%) patients and clinical success in 13/16 (81.3%) patients with P. aeruginosa; corresponding rates were 4/7 (57.1%) and 6/7 (85.7%) for meropenem. Cefepime-taniborbactam demonstrated efficacy in adult cUTI patients with cefepime-, multidrug-, and carbapenem-resistant pathogens including pathogens with ESBL, AmpC, and carbapenemase genes. CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT03840148.

Insights and Opinions of Critical Care Healthcare Professionals in the Management of Carbapenem-resistant Enterobacteriaceae Cases and Antibiotic-Resistant Infections in the Intensive Care Unit Setting: A Survey-Based Approach.

INTRODUCTION: A survey-based approach to managing antibiotic-resistant infections in the intensive care unit (ICU) setting, with a focus on carbapenem-resistant Enterobacteriaceae (CRE) cases, was conducted. Among CRE, New Delhi metallo-ß-lactamase 1 (NDM-1) is a carbapenemase that is resistant to ß-lactam antibiotics and has a broader spectrum of antimicrobial resistance than other carbapenemase types. The article explains that healthcare-associated infections (HAIs) are a significant problem, particularly in low- and middle-income countries, and that carbapenem in combination with other antibiotics are the most potent class of antimicrobial agents effective in treating life-threatening bacterial infections, including those caused by resistant strains. AIM: The survey aimed to gather critical care healthcare professionals (HCPs') opinions on their current practices in managing infections acquired in the hospital and ICU settings, with a focus on CRE cases, specifically NDM-1 and other antibiotic-resistant infections. METHODS: Responses from critical care healthcare professionals, including online surveys and in-person interviews, to gain insights into the management of infections caused by multidrug-resistant bacteria. The findings related to the insights on the prevalence of bacterial flora, clinical experiences on efficacy and safety of meropenem sulbactam ethylenediaminetetraacetic acid (EDTA) (MSE) in CRE cases, and various combination therapies of antibiotics used to treat antibiotic-resistant infections in ICU setting were evaluated. RESULTS: Klebsiella pneumoniae bacteria were the most common bacteria in cultures, followed by Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii. NDM-1 was the type of carbapenemase found in around 50% of CRE patients. MSE is among the most preferred antibiotics besides colistin, polymyxin B, and ceftazidime avibactum for CRE cases and specifically for NDM-1 cases due to its high rate of efficacy and safety. CONCLUSION: The article concludes with a discussion on the antibiotics used in response to CRE cases, reporting that critical care HCP considers MSE with high efficacy and safe antibiotic combination and was used as both monotherapy and in combination with other antibiotics. The survey highlights the need for exploring and better understanding the role of MSE in the management of CRE infections, especially in NDM-1.

Cefepime-taniborbactam and CERTAIN-1: Can we treat carbapenem-resistant infections?

Wagenlehner and colleagues1 demonstrated non-inferiority and superiority with respect to a primary endpoint of composite success (microbiological plus clinical) of cefepime/taniborbactam vs. meropenem in treating complicated urinary tract infections and acute pyelonephritis caused by carbapenem-susceptible gram-negative bacteria in adults. A major area of interest in real-world application of cefepime/taniborbactam is its potential role in treating carbapenem-resistant infections, which deserves further investigation.

Changes of PK/PD of Meropenem in patients with abdominal septic shock and exploration of clinical rational administration plan: a prospective exploratory study.

This study aimed to explore the changes of pharmacokinetic parameters after meropenem in patients with abdominal septic shock after gastrointestinal perforation, and to simulate the probability of different dosing regimens achieving different pharmacodynamic goals. The study included 12 patients, and utilized high performance liquid chromatography-tandem mass spectrometry to monitor the plasma concentration of meropenem. The probability of target attainment (PTA) for different minimum inhibitory concentration (MIC) values and %fT > 4MIC was compared among simulated dosing regimens. The results showed that in 96 blood samples from 12 patients, the clearance (CL) of meropenem in the normal and abnormal creatinine clearance subgroups were 7.7 ± 1.8 and 4.4 ± 1.1 L/h, respectively, and the apparent volume of distribution (Vd) was 22.6 ± 5.1 and 17.2 ± 5.8 L, respectively. 2. Regardless of the subgroup, 0.5 g/q6h infusion over 6 h regimen achieved a PTA > 90% when MIC ≤ 0.5 mg/L. 1.0 g/q6h infusion regimen compared with other regimen, in most cases, the probability of making PTA > 90% is higher. For patients at low MIC, 0.5 g/q6h infusion over 6 h may be preferable. For patients at high MIC, a dose regimen of 1.0 g/q6 h infusion over 6 h may be preferable. Further research is needed to confirm this exploratory result.

[A case of acute purulent otitis media complicated by atypical mastoiditis on the background of an unverified HIV infection]. / Sluchai ostrogo gnoinogo srednego otita, oslozhnennogo atipichnym mastoiditom, na fone neverifitsirovannoi VICh-infektsii.

According to the literature, acute otitis media is complicated by mastoiditis in 0.15-1% of cases. In turn, mastoiditis can be complicated by meningitis, encephalitis, abscess of temporal lobe of brain and cerebellum, epidural and subdural abscesses, facial nerve paresis, labyrinthitis, phlegmon of soft tissues of neck, as well as subperiosteal abscess, which makes 7% in the structure of mastoiditis complications. Nowadays, when doctors have a wide range of antibacterial preparations at their disposal, a complicated course of acute otitis media and further mastoiditis is caused both by an aggressive atypical infectious agent and immunocompromised status of a patient. The article deals with a clinical case of a prolonged course of acute otitis media complicated by mastoiditis and subperiosteal abscess against the background of outpatient courses of antibacterial therapy. The examination revealed an atypical pathogen of otitis media Pseudomonas aeruginosa and HIV-positive status of the patient, previously unknown. Timely surgical intervention and the right combination of antibacterial drugs, meropenem and ciprofloxacin, prevented the development of intracranial and septic complications, despite the presence of multiple foci of bone destruction of the mastoid process and temporal bone pyramid, bordering the middle fossa and sigmoid sinus, according to multispiral head computed tomography. As a part of additional examination in the Center for AIDS and Infectious Diseases Prevention and Control, the patient was diagnosed with HIV infection, clinical stage 4C, progressing phase on the background of absence of antiretroviral therapy, and the necessary amount of treatment was prescribed.