Voriconazole treatment of Candida tropicalis meningitis: persistence of (1,3)-b-D-glucan in the cerebrospinal fluid is a marker of clinical and microbiological failure

Introduction: Infections are still the most common complications of cerebral shunt procedures. Even though fungal etiologies are considered to be rare, they are associated with significant morbidity and mortality. Due to their uncommonness, diagnostic procedures and optimal therapy are poorly defined. We report a case of Candida tropicalis infection of ventriculo-peritoneal cerebrospinal fluid (CSF) shunt in a 49-year-old immune competent male treated with voriconazole (VOR). Methods: Microbiological and CSF markers (1,3-b-D-glucan-BDG) of fungal infection, biofilm production capacity, sensitivity of serial isolates of the pathogen, and the concentration of the antifungal drug have been monitored and related to the clinical course of this infection. Results: Despite appropriate treatment with VOR, in terms of adequate achieved CSF drug concentrations and initial effective therapeutic response, loss of VOR susceptibility of the C tropicalis and treatment failure were observed. Conclusion: Biofilm production of the C. tropicalis isolate might have had a significant role in treatment failure. Of interest, clinical and microbiological unfavorable outcome was anticipated by persistence of BDG in CSF. Rising titers of this marker were associated with relapse of fungal infection

Biotimer assay: A reliable and rapid method for the evaluation of central venous catheter microbial colonization

Adherent bacteria and biofilm frequently colonize central venous catheters (CVCs). CVC colonization is correlated to infections and particularly to bloodstream ones. The classical microbiological methods to determine of CVC colonization are not fully reliable and are time-consuming. BioTimer Assay (BTA) is a biological method already used to count bacteria adherent to abiotic surfaces and biofilm without sample manipulation. BTA employs specific reagents whose color changed according to bacterial metabolism. BTA is based on the principle that a metabolic reaction will be faster when more bacteria are present in the sample. Therefore, the time required for color changes of BTA reagents determines the number of bacteria present in the sample through a correlation line. Here, for the first time, we applied BTA and a specifically developed laboratory procedure to evaluate CVC colonization in comparison with the routine microbiological method (RMM). 125 CVCs removed from patients for suspected catheter-related bloodstream infection (CRBSI) or at hospital discharge were examined. BTA was reliable in assessing sterility and CVC colonization (100% agreement with RMM) and in recognizing the presence of fermenting or non-fermenting bacteria (97.1% agreement with RMM) shortening the analytical time by between 2- and 3-fold. Moreover, the reliability of BTA as early alert of CRBSI was evaluated. The sensitivity, specificity, positive, and negative predictive values for BTA as an early alert of CRBSI were 100, 40.0, 88.8 and 100%, respectively. In conclusion, BTA and the related laboratory procedure should be incorporated into routine microbiological methods since it can be considered a reliable tool to evaluate CVC colonization in a very short time and a rapid alert for CRBSIs

Ceftazidime-avibactam resistance in Klebsiella pneumoniae sequence type 37: a decade of persistence and concealed evolution

The first reports of carbapenem-resistant Enterobacterales in our hospital date back to 2006. In that period, few ertapenem-resistant but meropenem-susceptible Klebsiella pneumoniae isolates belonging to sequence type (ST) 37 were retrieved from clinical samples. These strains produced the CTX-M-15 extended spectrum β-lactamase, OmpK35 was depleted due to a nonsense mutation, and a novel OmpK36 variant was identified. Yet, starting from 2010, Klebsiella pneumoniae carbapenemase (KPC)-producing ST512 isolates started prevailing and ST37 vanished from sight. Since 2018 the clinical use of the combination of ceftazidime-avibactam (CZA) has been introduced in clinical practice for the treatment of bacteria producing serine-β-lactamases, but KPC-producing, CZA-resistant K. pneumoniae are emerging. In 2021, four CZA-resistant ST37 isolates producing KPC variants were isolated from the same number of patients. blaKPC gene cloning in Escherichia coli was used to define the role of those KPC variants on CZA resistance, and whole genome sequencing was performed on these isolates and on three ST37 historical isolates from 2011. CZA resistance was due to mutations in the blaKPC genes carried on related pKpQIL-type plasmids, and three variants of the KPC enzyme have been identified in the four ST37 strains. The four ST37 isolates were closely related to each other and to the historical isolates, suggesting that ST37 survived without notice in our hospital for 10 years, waiting to re-emerge as a CZA-resistant K. pneumoniae clone. The ancestor of these contemporary isolates derives from ST37 wild-type porin strains, with no other mutations in chromosomal genes involved in conferring antibiotic resistance (parC, gyrA, ramR, mgrB, pmrB)

Genome-based retrospective analysis of a Providencia stuartii outbreak in Rome, Italy. Broad spectrum IncC plasmids spread the NDM carbapenemase within the hospital

Providencia stuartii is a member of the Morganellaceae family, notorious for its intrinsic resistance to several antibiotics, including last-resort drugs such as colistin and tigecycline. Between February and March 2022, a four-patient outbreak sustained by P. stuartii occurred in a hospital in Rome. Phenotypic analyses defined these strains as eXtensively Drug-Resistant (XDR). Wholegenome sequencing was performed on the representative P. stuartii strains and resulted in fully closed genomes and plasmids. The genomes were highly related phylogenetically and encoded various virulence factors, including fimbrial clusters. The XDR phenotype was primarily driven by the presence of the (NDM)-N-bla- 1 metallo- beta-lactamase alongside the rmtC 16S rRNA methyltransferase, conferring resistance to most beta-lactams and every aminoglycoside, respectively. These genes were found on an IncC plasmid that was highly related to an NDM-IncC plasmid retrieved from a ST15 Klebsiella pneumoniae strain circulating in the same hospital two years earlier. Given its ability to acquire resistance plasmids and its intrinsic resistance mechanisms, P. stuartii is a formidable pathogen. The emergence of XDR P. stuartii strains poses a significant public health threat. It is essential to monitor the spread of these strains and develop new strategies for their control and treatment

Multiplicity of blaKPC genes and pKpQIL plasmid plasticity in the development of ceftazidime-avibactam and Meropenem coresistance in Klebsiella pneumoniae sequence type 307

In 2021, Klebsiella pneumoniae sequence type 307 (ST307) strains causing pulmonary and bloodstream infections identified in a hospital in Rome, Italy, reached high levels of resistance to ceftazidime-avibactam (CZA). One of these strains reached high levels of resistance to both CZA and carbapenems and carried two copies of bla(KPC-3) and one copy of bla(KPC-31) located on plasmid pKpQIL. The genomes and plasmids of CZA-resistant ST307 strains were analyzed to identify the molecular mechanisms leading to the evolution of resistance and compared with ST307 genomes at local and global levels. A complex pattern of multiple plasmids in rearranged configurations, coresident within the CZA-carbapenem-resistant K. pneumoniae strain, was observed. Characterization of these plasmids revealed recombination and segregation events explaining why K. pneumoniae isolates from the same patient had different antibiotic resistance profiles. This study illustrates the intense genetic plasticity occurring in ST307, one of the most worldwide-diffused K. pneumoniae high-risk clones.In 2021, Klebsiella pneumoniae sequence type 307 (ST307) strains causing pulmonary and bloodstream infections identified in a hospital in Rome, Italy, reached high levels of resistance to ceftazidime-avibactam (CZA). One of these strains reached high levels of resistance to both CZA and carbapenems and carried two copies of bla(KPC-3) and one copy of bla(KPC-31) located on plasmid pKpQIL

Clinical characteristics and outcome of ceftazidime/avibactam-resistant Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae infections. A retrospective, observational, 2-center clinical study

Background Recently, Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPC-Kp) with resistance to ceftazidime/avibactam (CZA-R) has been described, including KPC variants that restore carbapenem susceptibility. The aim of the study was to analyze the clinical characteristics and outcomes of infections caused by CZA-R KPC-Kp. Methods From 2019 to 2021, a retrospective 2-center study including patients with infections due to CZA-R KPC-Kp hospitalized at 2 academic hospitals in Rome was conducted. Demographic and clinical characteristics were collected. Principal outcome was 30-day all-cause mortality. Statistical analyses were performed with Stata-IC17 software. Results Overall, 59 patients were included (mean age, 64.4 & PLUSMN; 14.6 years; mean Charlson comorbidity index score, 4.5 & PLUSMN; 2.7). Thirty-four patients (57.6%) had infections caused by CZA-R and meropenem (MEM)-susceptible strains. A previous CZA therapy was observed in 40 patients (67.8%), mostly in patients with MEM-susceptible KPC variant (79.4% vs 52%, P = .026). Primary bacteremia was observed in 28.8%, followed by urinary tract infections and pneumonia. At infection onset, septic shock was present in 15 subjects (25.4%). After adjustment for confounders, only the presence of septic shock was independently associated with mortality (P = .006). Conclusions Infections due to CZA-R KPC-Kp often occur in patients who had previously received CZA, especially in the presence of strains susceptible to MEM. Nevertheless, one-third of patients had never received CZA before KPC-Kp CZA-R. Since the major driver for mortality was infection severity, understanding the optimal therapy in patients with KPC-Kp CZA-R infections is of crucial importance.Clinical characteristics and outcomes of infections caused by ceftazidime/avibactam-resistant (CZA-R) Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae were analyzed. Ceftazidime/avibactam-resistant and meropenem-susceptible KPC variants accounted for more than half of patients. Infections due to CZA-R KPC-Kp often occur in patients who had previously received CZA, especially in the presence of strains susceptible to meropenem. Nevertheless, one-third of patients had never received CZA before isolation of CZA strains. Infection severity was the only independent predictor of 30-day mortality

Klebsiella pneumoniae infections in COVID-19 patients: a two-month retrospective analysis in an Italian hospital

Italy has experienced one of the harshest and earliest COVID-19 epidemics, with the number of patients infected that followed, from the end of February up to the end of March, an exponential trend [1]. Between the 6 March and the 2 May, 394 patients were confirmed positive for SARS-CoV-2 at the University Hospital of Rome Policlinico Umberto I (PUI) [2]. At the PUI, 5 COVID-19 devoted wards were organized, including two brand new ICUs, counting 32 dedicated to COVID-19 patients: the first was the old general ICU converted into a dedicated COVID-19 ICU, while the second was created in the spaces of four operating rooms (new ICU). In the period of this study, a total of 80 COVID-19-affected patients were hospitalized in the two ICUs at PUI. Among them, 65 patients were screened for carbapenemase producing Enterobacterales (CPE) colonization (Brilliance™ CRE medium plates, Oxoid LTD, Basingstoke, UK): 41 out of 47 SARS-CoV-2 patients hospitalised in the old ICU and 24 out of 33 in the new one. Carbapenemase-producing K. pneumoniae were detected in 14/41 patients (34%) only in the old ICU. No CPE were detected from rectal swabs tested in patients hospitalized in the new ICU. In the same period, 11 CPEs were identified from the 39 rectal swabs out of 48 SARS-CoV-2-negative patients (28%) hospitalized in the non-COVID-ICU of the same hospital. Seven COVID-19 patients developed CPE co-infection (5 bronchoalveolar lavages and 2 blood cultures tested positives for carbapenemase-producing K. pneumoniae), while in the non-COVID-19 ICU 7 bloodstream infections (BSIs) also occurred (Table 1). Symptomatic patients were successfully treated with ceftazidime-avibactam

Impact of Initial Antifungal Therapy on the Outcome of Patients With Candidemia and Septic Shock Admitted to Medical Wards: A Propensity Score-Adjusted Analysis

Echinocandins are recommended as firstline therapy in patients with candidemia. However, there is debate on their efficacy in survival outcomes. The aim of this study is to evaluate whether the choice of initial antifungal therapy improves mortality in patients with candidemia in relation to the presence of septic shock

Impact of Initial Antifungal Therapy on the Outcome of Patients With Candidemia and Septic Shock Admitted to Medical Wards: A Propensity Score-Adjusted Analysis

13noBACKGROUND: Echinocandins are recommended as firstline therapy in patients with candidemia. However, there is debate on their efficacy in survival outcomes. The aim of this study is to evaluate whether the choice of initial antifungal therapy improves mortality in patients with candidemia in relation to the presence of septic shock. METHODS: Patients with candidemia hospitalized in internal medicine wards of 5 tertiary care centers were included in the study (December 2012-December 2014). Patient characteristics, therapeutic interventions, and outcome were reviewed. Propensity score (PS) was used as a covariate of the multivariate analysis to perform a stratified analysis according to PS quartiles and to match patients receiving "echinocandins" or "azoles." RESULTS: Overall, 439 patients with candidemia were included in the study. A total of 172 (39.2%) patients had septic shock. Thirty-day mortality was significantly higher in patients with septic shock (45.3%) compared with those without septic shock (31.5%; P = .003). Among patients with septic shock, the use of echinocandins in the first 48 hours, compared with azoles, did not affect 30-day mortality in the PS-adjusted Cox regression analysis (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.37-1.59; P = .48), the PS-stratified analysis, or the logistic regression model in matched cohorts (adjusted HR, 0.92; 95% CI, 0.51-1.63; P = .77). CONCLUSIONS: Echinocandin therapy seems not to improve the outcome of non-intensive care unit patients with septic shock due to candidemia. These findings support the urgent need of further studies in this patient population.openopenFalcone, Marco; Giusy, Tiseo; Gutiérrez-Gutiérrez, Belen; Giammarco, Raponi; Paolo, Carfagna; Chiara, Rosin; Roberto, Luzzati; Diego, Delle Rose; Massimo, Andreoni; Alessio, Farcomeni; Mario, Venditti; Rodríguez-Baño, Jesus; Menichetti, FrancescoMarco, Falcone; Tiseo, Giusy; Belen, Gutiérrez-Gutiérrez; Raponi, Giammarco; Carfagna, Paolo; Rosin, Chiara; Luzzati, Roberto; Delle Rose, Diego; Andreoni, Massimo; Farcomeni, Alessio; Venditti, Mario; Jesus, Rodríguez-Baño; Francesco, Menichett

The role of teicoplanin in the treatment of SARS-CoV-2 infection: a retrospective study in critically ill COVID-19 patients (Tei-COVID Study)

Teicoplanin has a potential antiviral activity expressed against SARS-CoV-2 and was suggested as a complementary option to treat COVID-19 patients. In this multicentric, retrospective, observational research the aim was to evaluate the impact of teicoplanin on the course of COVID-19 in critically ill patients