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1.
Diagn Microbiol Infect Dis ; 109(3): 116307, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38733753

ABSTRACT

The nocardiae are a complex group of bacteria belonging to the aerobic saprophytes actinomycetes. Although nocardiosis typically occurs in immunocompromised patients, infection may occasionally develop in immunocompetent patients as well. Here we describe a rare case of primary cutaneous nocardiosis due to Nocardia vinacea in an immunocompetent 79-year-old patient. Since cutaneous nocardiosis presents variably and mimics other cutaneous infections, acid-fast and Gram stainings on clinical samples are significant to obtain a rapid and presumptive diagnosis.


Subject(s)
Nocardia Infections , Nocardia , Skin Diseases, Bacterial , Humans , Nocardia Infections/diagnosis , Nocardia Infections/microbiology , Nocardia Infections/drug therapy , Nocardia/isolation & purification , Nocardia/genetics , Nocardia/classification , Aged , Skin Diseases, Bacterial/microbiology , Skin Diseases, Bacterial/diagnosis , Skin Diseases, Bacterial/drug therapy , Male , Anti-Bacterial Agents/therapeutic use , Skin/microbiology , Skin/pathology , Immunocompetence
2.
Article in English | MEDLINE | ID: mdl-38376634

ABSTRACT

PURPOSE: Real-world experience with meropenem/vaborbactam (M/V) is limited. Our aim is to report a clinical experience of M/V in the treatment of resistant Gram-negative bacilli. METHODS: This is a prospective observational study including patients hospitalized in the University Hospital of Pisa (March 2021-Jan 2023) with infections by both extended-spectrum ß-lactamases (ESBL)-producing Enterobacterales and carbapenem-resistant Klebsiella pneumoniae (Kp) treated with M/V. The primary outcome measure was clinical success, defined as a composite of survival, resolution of signs and symptoms and absence of microbiological failure at day 30 from infection onset. A multivariable regression analysis was performed to identify factors associated with clinical failure. Odds ratio (OR) with 95% confidence intervals (CI) was calculated. RESULTS: A total of 104 patients who received M/V were included: 24/104 (23.1%) infections were caused by ESBL non-hypervirulent Enterobacterales, 17/104 (16.3%) by ESBL-producing hypervirulent Klebsiella pneumoniae (hvKp) and 63/104 (60.6%) by CRE. The most common infections were bloodstream infections, followed by urinary tract infections, hospital-acquired pneumonia, intra-abdominal infections and others. Septic shock occurred in 16/104 (15.4%) patients. Clinical success was achieved in 77% of patients, and 30-day mortality rate was 15.4%. In patients with KPC-producing Kp infections, clinical success and 30-day mortality rates were 82% and 11.5%, respectively. On multivariable analysis, SOFA score (OR 1.32, 95% CI 1.02-1.7, p=0.032) was independently associated with clinical failure, while source control (OR 0.16, 95% CI 0.03-0.89, p=0.036) was protective. CONCLUSIONS: M/V is a promising therapeutic option against infections caused by difficult-to-treat ESBL-producing Enterobacterales and CR-Kp.

3.
Clin Infect Dis ; 2023 Nov 30.
Article in English | MEDLINE | ID: mdl-38036465

ABSTRACT

BACKGROUND: Metallo-ß-lactamases (MBL)-producing Enterobacterales are increasing worldwide. Our aim was to describe clinical features, treatments and outcomes of infections by MBL-Enterobacterales. METHODS: Prospective observational study conducted in the Pisa University Hospital (Jan 2019-Oct 2022) including patients with MBL-producing Enterobacterales infections. The primary outcome measure was 30-day mortality. A multivariable Cox regression analysis was performed to identify factors associated with 30-day mortality. Adjusted hazard ratio (aHR) (95% confidence intervals, CI) were calculated. RESULTS: 343 patients were included: 15 VIM- and 328 NDM-producing Enterobacterales infections. Overall, 199 (58%) were bloodstream infections, 60 (17.5%) hospital-acquired/ventilator-associated pneumonias, 60 (17.5%) complicated urinary tract infections, 13 (3.8%) intra-abdominal infections, 11 (3.2%) skin and soft tissue infections. Thirty-day mortality was 29.7%. Thirty-two patients did not receive in vitro active antibiotic therapy, 215/343 (62.7%) received ceftazidime-avibactam (CZA) plus aztreonam (ATM), 33/343 (9.6%) cefiderocol-containing regimens, 26/343 (7.6%) colistin-containing regimens and 37 (10.8%) other active antibiotics. On multivariable analysis, septic shock (aHR 3.57, 95% CI 2.05-6.23, p<0.001) and age (aHR 1.05, 95% CI 1.03-1.08, p<0.001) were independently associated with 30-day mortality, while in vitro active antibiotic therapy within 48 hours from infection (aHR 0.48, 95% CI 0.26-0.8, p=0.007) and source control (aHR 0.43, 95% CI 0.26-0.72, p=0.001) were protective factors. Sensitivity analysis showed that CZA plus ATM compared to colistin was independently associated with reduced 30-day mortality (aHR 0.39, 95% CI 0.18-0.86, p=0.019). Propensity score analyses confirmed these findings. CONCLUSIONS: MBL-CRE infections are associated with high 30-day mortality rates. Patients with MBL-producing Enterobacterales infections should received early active antibiotic therapy.

5.
JAC Antimicrob Resist ; 5(3): dlad078, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37325251

ABSTRACT

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) infections are associated with high mortality rates. The optimal treatment regimen for CRAB has not been defined. Cefiderocol has been recently introduced in the armamentarium against CRAB but there is concern about treatment-emergent resistance. Since mortality rates in CRAB infections remain high, further antibiotic options are needed. Methods: We report a case of severe infection by CRAB resistant to both colistin and cefiderocol treated with sulbactam/durlobactam and describe the molecular features of the strain. Susceptibility to cefiderocol was detected by disc diffusion according to EUCAST breakpoints. Susceptibility to sulbactam/durlobactam was determined by Etest according to preliminary breakpoints provided by Entasis Therapeutics. Whole Genome Sequencing (WGS) of the CRAB isolate was performed. Results: A burn patient with ventilator-associated pneumonia by CRAB resistant to colistin and cefiderocol received sulbactam/durlobactam as compassionate use. She was alive after 30 days from the end of therapy. Complete microbiological eradication of CRAB was achieved. The isolate harboured blaADC-30, blaOXA-23 and blaOXA-66. A missense mutation in PBP3 was detected. The isolate harboured a mutation in the TonB-dependent siderophore receptor gene piuA that showed a frameshift mutation causing a premature stop codon (K384fs). Moreover, the fepA gene, which is orthologous to pirA, was interrupted by a transposon insertion P635-ISAba125 (IS30 family). Conclusions: Further treatment options for severe infections by CRAB resistant to all available antibiotics are urgently needed. Sulbactam/durlobactam may be a future option against MDR A. baumannii.

8.
BMC Microbiol ; 22(1): 143, 2022 05 21.
Article in English | MEDLINE | ID: mdl-35597925

ABSTRACT

BACKGROUND: The current diagnostic gold standard for Pneumocystis jirovecii is represented by microscopic visualization of the fungus from clinical respiratory samples, as bronchoalveolar-lavage fluid, defining "proven" P. jirovecii pneumonia, whereas qPCR allows defining "probable" diagnosis, as it is unable to discriminate infection from colonization. However, molecular methods, such as end-point PCR and qPCR, are faster, easier to perform and interpret, thus allowing the laboratory to give back the clinician useful microbiological data in a shorter time. The present study aims at comparing microscopy with molecular assays and beta-D-glucan diagnostic performance on bronchoalveolar-lavage fluids from patients with suspected Pneumocystis jirovecii pneumonia. Bronchoalveolar-lavage fluid from eighteen high-risk and four negative control subjects underwent Grocott-Gomori's methenamine silver-staining, end-point PCR, RT-PCR, and beta-D-glucan assay. RESULTS: All the microscopically positive bronchoalveolar-lavage samples (50%) also resulted positive by end-point and real time PCR and all, but two, resulted positive also by beta-D-glucan quantification. End-point PCR and RT-PCR detected 10 (55%) and 11 (61%) out of the 18 samples, respectively, thus showing an enhanced sensitivity in comparison to microscopy. All RT-PCR with a Ct < 27 were confirmed microscopically, whereas samples with a Ct ≥ 27 were not. CONCLUSIONS: Our work highlights the need of reshaping and redefining the role of molecular diagnostics in a peculiar clinical setting, like P. jirovecii infection, which is a rare but also severe and rapidly progressive clinical condition affecting immunocompromised hosts that would largely benefit from a faster diagnosis. Strictly selected patients, according to the inclusion criteria, resulting negative by molecular methods could be ruled out for P. jirovecii pneumonia.


Subject(s)
Pneumonia, Pneumocystis , Bronchoalveolar Lavage Fluid/microbiology , Glucans , Humans , Immunocompromised Host , Pneumonia, Pneumocystis/diagnosis , Pneumonia, Pneumocystis/microbiology , Real-Time Polymerase Chain Reaction/methods , Sensitivity and Specificity , Therapeutic Irrigation
9.
Antimicrob Agents Chemother ; 66(5): e0214221, 2022 05 17.
Article in English | MEDLINE | ID: mdl-35311522

ABSTRACT

Cefiderocol may represent a therapeutic option for carbapenem-resistant Acinetobacter baumannii (CRAB) infections, but clinical data are limited. This is an observational retrospective study conducted in the University Hospital of Pisa including consecutive patients with CRAB infections (January 2020 to August 2021). Patients were divided in two study groups according to the antibiotic treatment received: cefiderocol- and colistin-containing regimens. The primary outcome was the 30-day mortality. A Cox regression analysis was performed to identify factors independently associated with 30-day mortality. A propensity score analysis using inverse probability of treatment weighting (IPTW) was also performed. A total of 124 patients were included: 47 (37.9%) received cefiderocol, while 77 (62.1%) colistin-containing regimens. Overall, 79 (63.7%) patients had a bloodstream infection (BSI), 35 (28.5%) a ventilator-associated pneumonia (VAP) and 10 (8.1%) other infections. Thirty-day mortality was higher in patients receiving colistin- compared to those who received cefiderocol-containing regimens (55.8% versus 34%, P = 0.018). This difference was confirmed in patients with BSI, but not in those with VAP. On multivariable analysis, septic shock, SOFA score, and age were independently associated with 30-day mortality, while cefiderocol therapy was protective in an IPTW analysis (Hazard ratio 0.44, 95% confidence interval 0.22-0.66, P < 0.001). Nephrotoxicity was more common in the colistin group. Microbiological failure occurred in 17.4% of patients receiving cefiderocol versus 6.8% of those receiving colistin (P = 0.079). Among 8 cases in the cefiderocol group who experienced microbiological failure, 4 (50%) developed resistance to cefiderocol. Cefiderocol represents a promising therapeutic option in patients with severe CRAB infections. Randomized clinical trial in this specific patient population should confirm our findings.


Subject(s)
Acinetobacter baumannii , Pneumonia, Ventilator-Associated , Sepsis , Anti-Bacterial Agents/therapeutic use , Carbapenems/therapeutic use , Cephalosporins , Colistin/therapeutic use , Humans , Pneumonia, Ventilator-Associated/drug therapy , Retrospective Studies , Sepsis/drug therapy , Cefiderocol
10.
J Antimicrob Chemother ; 77(4): 1140-1145, 2022 03 31.
Article in English | MEDLINE | ID: mdl-35040981

ABSTRACT

OBJECTIVES: To report an outbreak of hypervirulent Klebsiella pneumoniae (hvKp) in COVID-19 patients. METHODS: Prospective, observational study including consecutive COVID-19 patients with hvKp infections admitted to the University Hospital of Pisa (Italy). Clinical data and outcome of patients were collected. All patients were followed-up to 30 days from the diagnosis of infection. Mortality within 30 days of the diagnosis of hvKp infection was reported. The hypermucoviscous phenotype was determined by the 'string test'. Molecular typing was performed on three strains collected during different periods of the outbreak. The strains underwent whole genome sequencing using the Illumina MiSeq instrument. The complete circular assemblies were also obtained for the chromosome and a large plasmid using the Unicycler tool. RESULTS: From November 2020 to March 2021, hvKp has been isolated from 36 COVID-19 patients: 29/36 (80.6%) had infections (15 bloodstream infections, 8 ventilator-associated pneumonias and 6 complicated urinary tract infections), while 7/36 (19.4%) had colonization (3 urine, 2 rectal and 2 skin). The isolates belonged to ST147 and their plasmid carried three replicons of the IncFIB (Mar), IncR and IncHI1B types and several resistance genes, including the rmpADC genes encoding enhancers of capsular synthesis. The hvKp isolates displayed an ESBL phenotype, with resistance to piperacillin/tazobactam and ceftolozane/tazobactam and susceptibility only to meropenem and ceftazidime/avibactam. The majority of patients were treated with meropenem alone or in combination with fosfomycin. Thirty-day mortality was 48.3% (14/29). CONCLUSIONS: ST147 ESBL-producing hvKp is associated with high mortality in COVID-19 patients. Strict microbiological surveillance and infection control measures are needed in this population.


Subject(s)
COVID-19 , Klebsiella Infections , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacterial Proteins/genetics , Humans , Klebsiella Infections/epidemiology , Klebsiella Infections/microbiology , Klebsiella pneumoniae , Prospective Studies
11.
Clin Microbiol Infect ; 28(2): 298.e1-298.e7, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34197935

ABSTRACT

OBJECTIVE: To investigate the hypothesis that intestinal colonization by different types of carbapenemase-resistant Klebsiella pneumoniae (CR-Kp) leads to different risks for bloodstream infections (BSI) caused by the same colonizing organism. METHODS: Prospective observational study including consecutive CR-Kp rectal carriers admitted to the Pisa University Hospital (December 2018 to December 2019). Patients underwent rectal swabbing with molecular testing for the different carbapenemases at hospital admission and during hospitalization. Rectal carriers were classified as: NDM, KPC, VIM and OXA-48. The primary end point was the rate of BSI by the same colonizing organism in each study group. A multivariate logistic regression analysis was performed to identify factors independently associated with the risk for BSI by the colonizing organism. RESULTS: Of 677 rectal carriers, 382/677 (56.4%) were colonized by NDM, 247/677 (36.5%) by KPC, 39/677 (5.8%) by VIM and 9/677 (1.3%) by OXA-48. Dissemination of NDM-Kp was mostly sustained by ST147, while KPC-Kp belonged to ST512. A higher rate of BSI was documented in NDM rectal carriers compared with KPC rectal carriers (59/382, 15.4% versus 20/247, 8.1%, p 0.004). Incidence rates of BSI per 100 patients/month were significantly higher in the NDM group (22.33, 95% CI 17.26-28.88) than in the KPC group (9.56, 95% CI 6.17-14.82). On multivariate analysis, multi-site extraintestinal colonization, solid organ transplantation, invasive procedures, intravascular device, admission to intensive care unit, cephalosporin, fluoroquinolones and NDM rectal colonization (OR 3.27, 95% CI 1.73-6.18, p < 0.001) were independently associated with BSI. CONCLUSIONS: NDM-Kp was associated with increased risk of BSI compared with KPC-Kp. This finding seems to be strongly related to the high-risk clone ST147.


Subject(s)
Klebsiella Infections , Sepsis , Anti-Bacterial Agents/therapeutic use , Bacterial Proteins/genetics , Cohort Studies , Humans , Klebsiella Infections/drug therapy , Klebsiella Infections/epidemiology , Klebsiella pneumoniae/genetics , Prospective Studies , Sepsis/drug therapy , beta-Lactamases/genetics
12.
Open Forum Infect Dis ; 8(6): ofab141, 2021 Jun.
Article in English | MEDLINE | ID: mdl-34189161

ABSTRACT

A 68-year-old man had recurrent bacteremia by Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae resistant to ceftazidime-avibactam and cefiderocol. The sequencing of a target region showed that it harbored a KPC-3 variant enzyme (D179Y; KPC-31), which confers resistance to ceftazidime-avibactam and restores meropenem susceptibility. The patient was successfully treated with meropenem-vaborbactam.

13.
J Antimicrob Chemother ; 76(4): 1078-1084, 2021 03 12.
Article in English | MEDLINE | ID: mdl-33374002

ABSTRACT

BACKGROUND: Bacterial and fungal superinfections may complicate the course of hospitalized patients with COVID-19. OBJECTIVES: To identify predictors of superinfections in COVID-19. METHODS: Prospective, observational study including patients with COVID-19 consecutively admitted to the University Hospital of Pisa, Italy, between 4 March and 30 April 2020. Clinical data and outcomes were registered. Superinfection was defined as a bacterial or fungal infection that occurred ≥48 h after hospital admission. A multivariate analysis was performed to identify factors independently associated with superinfections. RESULTS: Overall, 315 patients with COVID-19 were hospitalized and 109 episodes of superinfections were documented in 69 (21.9%) patients. The median time from admission to superinfection was 19 days (range 11-29.75). Superinfections were caused by Enterobacterales (44.9%), non-fermenting Gram-negative bacilli (15.6%), Gram-positive bacteria (15.6%) and fungi (5.5%). Polymicrobial infections accounted for 18.3%. Predictors of superinfections were: intestinal colonization by carbapenem-resistant Enterobacterales (OR 16.03, 95% CI 6.5-39.5, P < 0.001); invasive mechanical ventilation (OR 5.6, 95% CI 2.4-13.1, P < 0.001); immunomodulatory agents (tocilizumab/baricitinib) (OR 5.09, 95% CI 2.2-11.8, P < 0.001); C-reactive protein on admission >7 mg/dl (OR 3.59, 95% CI 1.7-7.7, P = 0.001); and previous treatment with piperacillin/tazobactam (OR 2.85, 95% CI 1.1-7.2, P = 0.028). Length of hospital stay was longer in patients who developed superinfections ompared with those who did not (30 versus 11 days, P < 0.001), while mortality rates were similar (18.8% versus 23.2%, P = 0.445). CONCLUSIONS: The risk of bacterial and fungal superinfections in COVID-19 is consistent. Patients who need empiric broad-spectrum antibiotics and immunomodulant drugs should be carefully selected. Infection control rules must be reinforced.


Subject(s)
COVID-19/complications , Cross Infection/microbiology , Superinfection/microbiology , Superinfection/virology , Aged , Aged, 80 and over , Bacterial Infections , Coinfection , Female , Hospitalization , Humans , Italy , Male , Middle Aged , Mycoses , Prospective Studies , Risk Factors
14.
J Antimicrob Chemother ; 76(4): 1025-1031, 2021 03 12.
Article in English | MEDLINE | ID: mdl-33378458

ABSTRACT

BACKGROUND: Avibactam is a ß-lactamase inhibitor that is combined with aztreonam against Enterobacterales co-expressing serine- and metallo-ß-lactamases (MBL). Optimal dosing of aztreonam with avibactam is not well-defined in critically ill patients and contingent on ceftazidime/avibactam product labelling. OBJECTIVES: To identify a pragmatic dosing strategy for aztreonam with avibactam to maximize the probability of target attainment (PTA). METHODS: We conducted a prospective observational pharmacokinetic study. Five blood samples were collected around the fourth dose of aztreonam or ceftazidime/avibactam and assayed for all three drugs. Population pharmacokinetic (PK) analysis coupled with Monte Carlo simulations were used to create a dosing nomogram for aztreonam and ceftazidime/avibactam based on drug-specific pharmacodynamic (PD) targets. RESULTS: A total of 41 participants (59% male) median age of 75 years (IQR 63-79 years) were enrolled. They were critically ill (46%) with multiple comorbidities and complications including burns (20%). Population PK analysis identified higher volume of distribution and lower clearance (CL) compared with typical value expectations for aztreonam and ceftazidime/avibactam. Estimated glomerular filtration (eGFR) rate using the CKD-EPI equation predicted CL for all three drugs. The need for high doses of aztreonam and ceftazidime/avibactam above those in the existing product labels are not predicted by this analysis with the exception of ceftazidime/avibactam for patients with eGFR of 6-15 mL/min, in whom suboptimal PTA of ≤71% is predicted. CONCLUSIONS: Pragmatic and lower daily-dose options are predicted for aztreonam and ceftazidime/avibactam when the eGFR is <90 mL/min. These options should be tested prospectively.


Subject(s)
Aztreonam , Ceftazidime , Aged , Anti-Bacterial Agents/therapeutic use , Azabicyclo Compounds , Drug Combinations , Female , Humans , Male , Microbial Sensitivity Tests , Middle Aged , beta-Lactamases
15.
Clin Infect Dis ; 72(11): 1871-1878, 2021 06 01.
Article in English | MEDLINE | ID: mdl-32427286

ABSTRACT

BACKGROUND: In vitro data support the use of combination of aztreonam (ATM) with ceftazidime-avibactam (CAZ-AVI), but clinical studies are lacking. The aim of our study was to compare the outcome of patients with bloodstream infections (BSIs) due to metallo-ß-lactamase (MBL)-producing Enterobacterales treated either with CAZ-AVI plus ATM or other active antibiotics (OAAs). METHODS: This was a prospective observational study including patients admitted to 3 hospitals in Italy and Greece. The primary outcome measure was 30-day all-cause mortality. Secondary outcomes were clinical failure at day 14 and length of stay after BSI diagnosis. Cox regression analysis including a propensity score (PS) for receiving CAZ-AVI + ATM was performed to evaluate primary and secondary outcomes. A PS-based matched analysis was also performed. RESULTS: We enrolled 102 patients with BSI; 82 had infections caused by NDM-producing (79 Klebsiella pneumoniae and 3 Escherichia coli) and 20 by VIM-producing (14 K. pneumoniae, 5 Enterobacter species, 1 Morganella morganii) strains. The 30-day mortality rate was 19.2% in the CAZ-AVI + ATM group vs 44% in the OAA group (P = .007). The PS-adjusted analysis showed that the use of CAZ-AVI + ATM was associated with lower 30-day mortality (hazard ratio [HR], 0.37 [95% confidence interval {CI}, .13-.74]; P = .01), lower clinical failure at day 14 (HR, 0.30 [95% CI, .14-.65]; P = .002), and shorter length of stay (subdistributional HR, 0.49 [95% CI, .30-.82]; P = .007). The PS-matched analysis confirmed these findings. CONCLUSIONS: The CAZ-AVI + ATM combination offers a therapeutic advantage compared to OAAs for patients with BSI due to MBL-producing Enterobacterales. Further studies are warranted.


Subject(s)
Aztreonam , Sepsis , Anti-Bacterial Agents/therapeutic use , Azabicyclo Compounds/therapeutic use , Aztreonam/therapeutic use , Ceftazidime/therapeutic use , Drug Combinations , Greece , Humans , Italy/epidemiology , Microbial Sensitivity Tests , Sepsis/drug therapy , beta-Lactamases
16.
Clin Infect Dis ; 72(11): 2021-2024, 2021 06 01.
Article in English | MEDLINE | ID: mdl-32941593

ABSTRACT

Ten critically ill patients with either bacteremia or ventilator-associated pneumonia caused by carbapenem-resistant Acinetobacter baumannii, Stenotrophomonas maltophilia, or New Delhi metallo-ß-lactamase-producing Klebsiella pneumoniae received cefiderocol. All strains had minimum inhibitory concentration ≤2 µg/mL. Thirty-day clinical success and survival rates were 70% and 90%, respectively. Two patients had a microbiological failure. Future prospective studies are warranted.


Subject(s)
Acinetobacter baumannii , Anti-Bacterial Agents/therapeutic use , Carbapenems , Cephalosporins , Humans , Intensive Care Units , Microbial Sensitivity Tests , Prospective Studies , beta-Lactamases , Cefiderocol
17.
Euro Surveill ; 25(48)2020 12.
Article in English | MEDLINE | ID: mdl-33272354

ABSTRACT

A large outbreak of New Delhi metallo-beta-lactamase (NDM)-1-producing Klebsiella pneumoniae sequence type (ST) 147 occurred in Tuscany, Italy in 2018-2019. In 2020, ST147 NDM-9-producing K. pneumoniae were detected at the University Hospital of Pisa, Tuscany, in two critically ill patients; one developed bacteraemia. Genomic and phylogenetic analyses suggest relatedness of 2018-2019 and 2020 strains, with a change from NDM-1 to NDM-9 in the latter and evolution by colistin, tigecycline and fosfomycin resistance acquisition.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bacteremia/drug therapy , Drug Resistance, Multiple, Bacterial/genetics , Klebsiella Infections/drug therapy , Klebsiella pneumoniae/genetics , Bacteremia/diagnosis , Humans , Italy , Klebsiella Infections/diagnosis , Klebsiella Infections/microbiology , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/isolation & purification , Male , Microbial Sensitivity Tests , Multilocus Sequence Typing , Phylogeny , Plasmids/genetics , beta-Lactamases/genetics
18.
Open Forum Infect Dis ; 7(2): ofaa011, 2020 Feb.
Article in English | MEDLINE | ID: mdl-32042848

ABSTRACT

Limited data about New Delhi metallo-ß-lactamase (NDM) bacteremia are available. Blood isolates from 40 patients with NDM bacteremia were studied for antibiotic susceptibility and whole-genomic sequencing. NDM bacteremia has high 30-day mortality. In most cases, aztreonam-avibactam is active in vitro. Ceftazidime-avibactam plus aztreonam may represent a feasible therapeutic option.

19.
Crit Care ; 24(1): 29, 2020 01 30.
Article in English | MEDLINE | ID: mdl-32000834

ABSTRACT

BACKGROUND: Bloodstream infections (BSIs) by Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (Kp) are associated with high mortality. The aim of this study is to assess the relationship between time to administration of appropriate antibiotic therapy and the outcome of patients with BSI due to KPC-Kp hospitalized in intensive care unit (ICU). METHODS: An observational study was conducted in the ICUs of two academic centers in Italy. Patients with KPC-Kp bacteremia hospitalized between January 2015 to December 2018 were included. The primary outcome was the relationship between time from blood cultures (BC) collection to appropriate antibiotic therapy and 30-day mortality. The secondary outcome was to evaluate the association of different treatment regimens with 30-day mortality and a composite endpoint (30-day mortality or nephrotoxicity). A Cox regression analysis to identify factors independently associated with 30-day mortality was performed. Hazard ratio (HR) and 95% confidence interval (CI) were calculated. RESULTS: A total of 102 patients with KPC-Kp BSI were included. The most common sources of infection were intra-abdominal (23.5%), urinary tract (20.6%), and skin and skin structure (17.6%). The 30-day mortality was 45%. Median time to appropriate antibiotic therapy was shorter in patients who survived (8.5 h [IQR 1-36]) versus those who died (48 h [IQR 5-108], p = 0.014). A propensity score matching showed that receipt of an in vitro active therapy within 24 h from BC collection was associated with lower 30-day mortality (HR = 0.36, 95% CI: 0.188-0.690, p = 0.0021). At Cox regression analysis, factors associated with 30-day mortality were primary bacteremia (HR 2.662 [95% CI 1.118-6.336], p = 0.027), cardiovascular disease (HR 2.196 [95% CI 1.082-4.457], p = 0.029), time (24-h increments) from BC collection to appropriate therapy (HR 1.382 [95% CI 1.132-1.687], p = 0.001), SOFA score (HR 1.122 [95% CI 1.036-1.216], p = 0.005), and age (HR 1.030 [95% CI 1.006-1.054], p = 0.012). Ceftazidime-avibactam-containing regimens were associated with reduced risk of composite endpoint (30-day mortality OR nephrotoxicity) (HR 0.231 [95% CI 0.071-0.745], p = 0.014) compared to colistin-containing regimens. CONCLUSIONS: Time to appropriate antibiotic therapy is an independent predictor of 30-day mortality in patients with KPC-Kp BSI. Appropriate antibiotic therapy should begin within 24 h from the collection of BC.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Bacteremia/drug therapy , Time Factors , Academic Medical Centers/organization & administration , Academic Medical Centers/statistics & numerical data , Adult , Aged , Anti-Bacterial Agents/therapeutic use , Bacteremia/etiology , Bacteremia/physiopathology , Bacterial Proteins/adverse effects , Female , Humans , Italy/epidemiology , Klebsiella Infections/drug therapy , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/pathogenicity , Male , Middle Aged , Outcome Assessment, Health Care/standards , Outcome Assessment, Health Care/statistics & numerical data , Propensity Score , Proportional Hazards Models , Retrospective Studies , Statistics, Nonparametric , beta-Lactamases/adverse effects
20.
New Microbiol ; 40(3): 161-164, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28513809

ABSTRACT

The mortality for carbapenem-resistant Klebsiella pneumoniae (KPC-Kp) infection ranges from 18 to 48% depending on the type of therapy. Mortality rates in hematologic patients are even higher, up to 85%. Gut decontamination with oral gentamicin might be an option to avoid a subsequent KPC-Kp infection in colonized patients. We treated 14 hematologic patients with oral gentamicin, 80 mg four times daily, for 7 to 25 days in order to eradicate KPC-Kp from the gut, starting oral gentamicin therapy when possible after the discontinuation of systemic antibiotic therapy. The overall decontamination rate in the entire study population was 71% (10/14). Out of the 4 patients who did not respond to oral gentamicin therapy, 1 KPC-Kp strain was gentamicin resistant and 4 patients received concomitant systemic antibiotic therapy (CSAT). One of these patients died from KPC-Kp sepsis. The decontamination rate was 90% (9/10) in patients receiving oral gentamicin only, versus 25% (1/4) in those also treated with CSAT. No new gentamicin-resistant KPC-Kp strain was isolated during oral gentamicin therapy Oral gentamicin might be useful for gut decontamination and prevention of KPC-Kp infection. This option should be considered in patients colonized by a gentamicin-susceptible KPC-Kp strain and not receiving CSAT.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Carbapenem-Resistant Enterobacteriaceae/drug effects , Gentamicins/therapeutic use , Klebsiella Infections/drug therapy , Klebsiella pneumoniae/drug effects , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/pharmacology , Carbapenems/pharmacology , Drug Resistance, Bacterial , Female , Gentamicins/pharmacology , Hematologic Diseases/complications , Humans , Klebsiella Infections/microbiology , Male , Middle Aged , Rectum/microbiology
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