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BMJ Paediatrics Open Dec 2023Antibacterial therapy plays a crucial role in neonatal infections. The efficacy of antibacterial agents is closely related to the actual dose given to neonates. So we...
BACKGROUND
Antibacterial therapy plays a crucial role in neonatal infections. The efficacy of antibacterial agents is closely related to the actual dose given to neonates. So we evaluated factors potentially affecting the actual dose of intravenous antibiotics during dispensing process in neonates.
METHODS
Meropenem, cefoperazone/sulbactam and piperacillin/tazobactam with two strengths were used to evaluate three methods. Method A (M) was diluted once and the volumes of 5% glucose for M were meropenem 4.00 mL, cefoperazone/sulbactam 3.00 mL, piperacillin/tazobactam 9.00 mL. Method B (M) differed by doubling the volume of 5% glucose. The difference in method C (M) involved diluting with 5% glucose twice. The concentrations were measured by high-performance liquid chromatography. Relative error (RE) was used to evaluate the preparation accuracy.
RESULTS
The RE values using M/M/M were: (1) meropenem 0.5 g: 15.1%, 8.0%, 10.4%; 0.25 g: 7.8%, 3.1%, 6.0%; (2) cefoperazone/sulbactam 1.5 g: 13.6%, 4.2%, 3.4%; 0.75 g: 8.8%, 3.5%, 4.0%; (3) piperacillin/tazobactam 4.5 g: 18.2%, 8.7%, 6.3%; 562.5 mg: 8.1%, 2.8%, 6.1%. M was better than M in all three drugs. No difference in RE values was found between single and double dilution, except meropenem with 0.25 g. Using M, meropenem and piperacillin/tazobactam with small drug strength had higher accuracy in preparation.
CONCLUSIONS
M was suitable for neonatal drug dispensing because of its high accuracy and simple operation. Drugs with small strength were promoted due to the high accuracy.
Topics: Infant, Newborn; Humans; Anti-Bacterial Agents; Meropenem; Cefoperazone; Sulbactam; Piperacillin; Piperacillin, Tazobactam Drug Combination; Glucose
PubMed: 38114241
DOI: 10.1136/bmjpo-2023-002299 -
Scientific Reports Aug 2023We analyzed 5 years (2016-2020) of nested Canadian data from the Study for Monitoring Antimicrobial Resistance Trends (SMART) to identify pathogen predominance and...
We analyzed 5 years (2016-2020) of nested Canadian data from the Study for Monitoring Antimicrobial Resistance Trends (SMART) to identify pathogen predominance and antimicrobial resistance (AMR) patterns of adult Gram-negative infections in Canadian health care and to complement other public surveillance programs and studies in Canada. A total of 6853 isolates were analyzed from medical (44%), surgical (18%), intensive care (22%) and emergency units (15%) and from respiratory tract (36%), intra-abdominal (25%), urinary tract (24%) and bloodstream (15%) infections. Overall, E. coli (36%), P. aeruginosa (18%) and K. pneumoniae (12%) were the most frequent isolates and P. aeruginosa was the most common respiratory pathogen. 18% of Enterobacterales species were ESBL positive. Collective susceptibility profiles showed that P. aeruginosa isolates were highly susceptible (> 95%) to ceftolozane/tazobactam and colistin, though markedly less susceptible (58-74%) to other antimicrobials tested. Multi-drug resistance (MDR) was present in 10% of P. aeruginosa isolates and was more frequent in those from respiratory infections and from ICU than non-ICU locations. Of P. aeruginosa isolates that were resistant to combinations of ceftazidime, piperacillin/tazobactam and meropenem, 73-96% were susceptible to ceftolozane/tazobactam over the period of the study. These national data can now be combined with clinical prediction rules and genomic data to enable expert antimicrobial stewardship applications and guide treatment policies to optimize adult patient care.
Topics: Adult; Humans; Anti-Bacterial Agents; Escherichia coli; Canada; Drug Resistance, Bacterial; Anti-Infective Agents; Tazobactam
PubMed: 37644048
DOI: 10.1038/s41598-023-40012-z -
Medicina (Kaunas, Lithuania) Jul 2023: () is an important nosocomial pathogen that not only possesses intrinsic resistance to many classes of antibiotics, but is also capable of rapidly developing...
: () is an important nosocomial pathogen that not only possesses intrinsic resistance to many classes of antibiotics, but is also capable of rapidly developing antimicrobial resistance during treatment. The aim of this study was to determine the characteristics of resistance of strains to -lactams and other tested antibiotics, to evaluate the associations between the phenotypes of resistance to -lactams and other tested antibiotics, and to evaluate the changes in antibiotic resistance of strains over 5 years by comparing the periods of 2016-2017 and 2020-2021. A total of 233 strains were isolated from different clinical specimens of patients treated at the Hospital of Lithuanian University of Health Sciences in 2016-2017 ( = 130) and 2021-2022 ( = 103). All clinical cultures positive for were analyzed. The type of -lactamase was detected by phenotypic methods using ESBL plus AmpC screen disk tests and the combination meropenem disk test. In both periods, all strains were resistant to ciprofloxacin; resistance to carbapenems, piperacillin/tazobactam, gentamicin, and tobramycin was noted in more than 80% of strains. A comparison of two periods showed that the percentages of strains producing two or three types of -lactamases were significantly greater in 2021-2022 than in 2016-2017 (94.2% and 5.8% vs. 17.7% and 2.3%, respectively, < 0.001). Isolates producing two or three types of -lactamases were more often resistant to tigecycline, tetracycline, and doxycycline than strains producing one type of -lactamase ( < 0.001). The frequency of isolation of strains producing two different types of -lactamases (AmpC plus KPC, AmpC plus ESBL, or ESBL plus KPC) or three types of -lactamases (AmpC, KPC, and ESBL) and the resistance rates to ampicillin/sulbactam, tigecycline, tetracycline, and doxycycline were significantly greater in 2020-2021 as compared with 2016-2017. The production of two or three types of -lactamases by strains was associated with higher resistance rates to tetracyclines.
Topics: Anti-Bacterial Agents; Doxycycline; Tetracycline; Tigecycline; Acinetobacter baumannii; Drug Resistance, Bacterial; Carbapenems
PubMed: 37629675
DOI: 10.3390/medicina59081386 -
Antibiotics (Basel, Switzerland) Nov 2023(1) Objectives: To describe the attainment of optimal pharmacokinetic/pharmacodynamic (PK/PD) targets in orthotopic liver transplant (OLT) recipients treated with...
Role of a Real-Time TDM-Based Expert Clinical Pharmacological Advice Program in Optimizing the Early Pharmacokinetic/Pharmacodynamic Target Attainment of Continuous Infusion Beta-Lactams among Orthotopic Liver Transplant Recipients with Documented or Suspected Gram-Negative Infections.
(1) Objectives: To describe the attainment of optimal pharmacokinetic/pharmacodynamic (PK/PD) targets in orthotopic liver transplant (OLT) recipients treated with continuous infusion (CI) beta-lactams optimized using a real-time therapeutic drug monitoring (TDM)-guided expert clinical pharmacological advice (ECPA) program during the early post-surgical period. (2) Methods: OLT recipients admitted to the post-transplant intensive care unit over the period of July 2021-September 2023, receiving empirical or targeted therapy with CI meropenem, piperacillin-tazobactam, meropenem-vaborbactam, or ceftazidime-avibactam optimized using a real-time TDM-guided ECPA program, were retrospectively retrieved. Steady-state beta-lactam (BL) and/or beta-lactamase inhibitor (BLI) plasma concentrations (C) were measured, and the C/MIC ratio was selected as the best PK/PD target for beta-lactam efficacy. The PK/PD target of meropenem was defined as being optimal when attaining a C/MIC ratio > 4. The joint PK/PD target of the BL/BLI combinations (namely piperacillin-tazobactam, ceftazidime-avibactam, and meropenem-vaborbactam) was defined as being optimal when the C/MIC ratio > 4 of the BL and the C/target concentration (C) ratio > 1 of tazobactam or avibactam, or the AUC/C ratio > 24 of vaborbactam were simultaneously attained. Multivariate logistic regression analysis was performed for testing potential variables that were associated with a failure in attaining early (i.e., at first TDM assessment) optimal PK/PD targets. (3) Results: Overall, 77 critically ill OLT recipients (median age, 57 years; male, 63.6%; median MELD score at transplantation, 17 points) receiving a total of 100 beta-lactam treatment courses, were included. Beta-lactam therapy was targeted in 43% of cases. Beta-lactam dosing adjustments were provided in 76 out of 100 first TDM assessments (76.0%; 69.0% decreases and 7.0% increases), and overall, in 134 out of 245 total ECPAs (54.7%). Optimal PK/PD target was attained early in 88% of treatment courses, and throughout beta-lactam therapy in 89% of cases. Augmented renal clearance (ARC; OR 7.64; 95%CI 1.32-44.13) and MIC values above the EUCAST clinical breakpoint (OR 91.55; 95%CI 7.12-1177.12) emerged as independent predictors of failure in attaining early optimal beta-lactam PK/PD targets. (4) Conclusion: A real-time TDM-guided ECPA program allowed for the attainment of optimal beta-lactam PK/PD targets in approximately 90% of critically ill OLT recipients treated with CI beta-lactams during the early post-transplant period. OLT recipients having ARC or being affected by pathogens with MIC values above the EUCAST clinical breakpoint were at high risk for failure in attaining early optimal beta-lactam PK/PD targets. Larger prospective studies are warranted for confirming our findings.
PubMed: 37998801
DOI: 10.3390/antibiotics12111599 -
BMC Infectious Diseases Jul 2023Leptospirosis is a zoonosis caused by spirochete "genus" leptospira. The clinical presentations of leptospirosis range from an influenza-like presentation of fever and... (Review)
Review
BACKGROUND
Leptospirosis is a zoonosis caused by spirochete "genus" leptospira. The clinical presentations of leptospirosis range from an influenza-like presentation of fever and myalgia, to severe forms. Leptospirosis can potentially lead to a misdiagnosis or delay in diagnosis when clinical similarities exist.
CASE PRESENTATION
A 63-year-old man presented with fever, shock and thrombocytopenia followed by diffuse pulmonary hemorrhage. Peripheral blood Metagenomic Next-generation Sequencing (mNGS) reported Leptospira interrogans. The patient was treated with piperacillin-tazobactam (TZP) plus doxycycline and improved dramatically after 7 days.
CONCLUSION
We conclude that leptospirosis can potentially lead to a misdiagnosis or delay in diagnosis. Correctly evaluation of thrombocytopenia in acute febrile illnesses facilitates the differential diagnosis of leptospirosis. mNGS can accurately detect Leptospira DNA during the early stage of the infection.
Topics: Male; Animals; Humans; Middle Aged; Shock, Septic; Leptospirosis; Zoonoses; Leptospira; Hemorrhage; Thrombocytopenia
PubMed: 37525113
DOI: 10.1186/s12879-023-08367-w -
Antibiotics (Basel, Switzerland) Dec 2023(1) Background: The widespread use of MALDI-TOF coupled to mass spectrometry has improved diagnostic accuracy by identifying uncommon bacteria. Among Enterobacterales,...
(1) Background: The widespread use of MALDI-TOF coupled to mass spectrometry has improved diagnostic accuracy by identifying uncommon bacteria. Among Enterobacterales, species have been seen to be implicated in several human infections, but their clinical and microbiological framework is currently based on a few anecdotal reports. (2) Methods: We conducted this five-year (2018-2023) single-center study aimed at investigating the prevalence and clinical and microbiological findings of species bloodstream infections. (3) Results: Among the 4996 bloodstream infection Gram-negative isolates collected during the study period, species accounted for 0.4% (n = 19) of isolates from 19 different patients, 5 of them being pediatric cases. Among species isolates, was the most frequently detected (45%; n = 9) followed by (30%; n = 6) and (15%; n = 3). Malignancy (35.7%) in adults and malignancy (40%) and cerebrovascular disease following meconium aspiration (40%) in pediatric patients as comorbidities and shivering and/or fever following parenteral infusion (36.8%) as a symptom/sign of species bloodstream infection onset were the most frequently observed clinical features. Among adults, primary bloodstream infection was the most frequent (50%), whereas among pediatric patients, the most commonly identified sources of infection were catheter-related (40%) and the respiratory tract (40%). Overall, species bloodstream infection isolates displayed high susceptibility to all the antibiotics except for ampicillin (63.2%), fosfomycin (73.7%), and piperacillin/tazobactam (84.2%). Targeted antibiotic treatment was prescribed as monotherapy for adults (71.4%) and combination therapy for pediatric patients (60%). The most prescribed antibiotic regimens were piperacillin/tazobactam (21.4%) in adults and meropenem- (40%) and aminoglycoside-containing (40%) antibiotics in pediatric patients. The overall 28-day all-cause mortality rate was 5.3% (n = 1). (4) Conclusions: The prevalence and 28-day mortality rate of species bloodstream infections were low. The prescription of targeted therapy including broad-spectrum antibiotics could indicate an underestimation of the specific involvement of the species in the onset of the disease, warranting further studies defining their pathogenic potential.
PubMed: 38136757
DOI: 10.3390/antibiotics12121723 -
The Journal of Antimicrobial... Mar 2024Treatment options for urinary tract infections (UTIs) caused by ESBL-producing Enterobacterales are limited. Moreover, evidence to support therapeutic decisions is...
OBJECTIVES
Treatment options for urinary tract infections (UTIs) caused by ESBL-producing Enterobacterales are limited. Moreover, evidence to support therapeutic decisions is lacking. This study assessed current treatment strategies and patient and pathogen characteristics in relation to clinical and microbiological outcomes.
METHODS
Patients with UTI caused by ESBL-producing Enterobacterales were prospectively recruited by investigators at 15 infectious disease hospital departments. Data were collected on patient characteristics, treatments, clinical and microbiological cure 10-14 days after the end of treatment, and relapse within 3 months. Bacterial isolates were subjected to MIC determination and WGS.
RESULTS
In total, 235 patients (107 febrile UTI, 128 lower UTI) caused by Escherichia coli (n = 223) and Klebsiella spp. (n = 12) were included. Clinical and microbiological cure rates were 83% and 64% in febrile UTI, and 79% and 65% in lower UTI. Great variability in treatments was observed, especially in oral therapy for febrile UTI. No difference was seen in clinical outcomes with piperacillin/tazobactam (n = 28) compared with carbapenems (n = 41). Pivmecillinam was frequently used in lower UTI (n = 62), and was also associated with high clinical cure rates when used as initial therapy (10/10) or follow-up (7/8) for febrile UTI. Recurrent infection, diabetes mellitus and urogenital disease were associated (P < 0.05) with clinical failure and relapse. In E. coli, ST131 was significantly associated with relapse, and haemolysin with microbiological failure or relapse.
CONCLUSIONS
Antibiotic treatments were highly variable. Patient and pathogen factors were identified as potential determinants of disease presentation and outcomes and may prove useful to guide individualized treatment and follow-up.
Topics: Humans; Amdinocillin Pivoxil; Escherichia coli; Fever; Gammaproteobacteria; Prospective Studies; Recurrence; Urinary Tract Infections
PubMed: 38197416
DOI: 10.1093/jac/dkad402 -
Antibiotics (Basel, Switzerland) Sep 2023Neonatal sepsis is an important cause of morbidity and mortality in neonatal intensive care units (NICUs). Continuous evaluation of antimicrobial resistance (AMR)...
Neonatal sepsis is an important cause of morbidity and mortality in neonatal intensive care units (NICUs). Continuous evaluation of antimicrobial resistance (AMR) profiles is advised to implement antimicrobial stewardship (AMS) programs and establish effective empiric antibiotic protocols. AMS may reduce AMR in NICUs and improve sepsis outcomes. In this retrospective observational study, we report data on culture-positive neonatal sepsis, assessing differences after the implementation of an AMS program (2011-2016 vs. 2017-2022). A total of 215 positive bacterial cultures from 169 infants were retrieved, with 79 early-onset (36.7%) and 136 late-onset (63.3%) sepsis episodes. Frequent causative agents for early-onset sepsis were and , all susceptible to empiric treatment. Late-onset sepsis was mainly caused by and . Aminoglycosides, cefotaxime, and piperacillin-tazobactam resistance among was substantially low; was mostly susceptible to oxacillin and vancomycin. There were no differences in mortality and multidrug-resistant pathogens rates between the two study periods. There were five episodes of fungal late-onset sepsis, mostly due to , of which one was fatal. The microbial distribution pattern and AMR profiles overlapped with other European studies. Because susceptibility patterns are rapidly changing worldwide, with the emerging threat of Methicillin-resistant and extended-spectrum beta-lactamases producers, infection prevention and control practices and AMS strategies require continuous optimization to limit selection pressure and AMR escalation.
PubMed: 37887188
DOI: 10.3390/antibiotics12101488 -
Frontiers in Microbiology 2023Carbapenem-resistant (CRPA) is a growing threat. It is urgent to investigate the multidrug resistance and high virulence of CRPA to provide a basis for infection...
Evaluation and analysis of multidrug resistance- and hypervirulence-associated genes in carbapenem-resistant strains among children in an area of China for five consecutive years.
INTRODUCTION
Carbapenem-resistant (CRPA) is a growing threat. It is urgent to investigate the multidrug resistance and high virulence of CRPA to provide a basis for infection control and rational use of antibiotics.
METHODS
A retrospective study of 56 nonduplicated CRPA isolates was conducted.
RESULTS
CRPA mainly came from the intensive care unit (ICU) and was mostly isolated from sputum samples. The carbapenem resistance rates of were 21.37% (2016), 10.62, 5.88, 10 and 13.87% from 2016 to 2020, respectively. Carbapenem-resistant enzymes and aminoglycoside-modifying enzyme-encoding genes were detected in all isolates, and extended-spectrum β-lactamase and cephalosporin enzyme-encoding genes were present in 96.43 and 80.38% of isolates, respectively. The detection rate of showed a statistically significant difference ( < 0.05) between the ICU and other wards. Genes related to biofilms, membrane channel proteins, I integrons and efflux systems were detected in all isolates, with detection rates greater than 90%. CRPA was strongly virulent, and over 80% of isolates carried hypervirulence-associated genes (, , , and ). The drug resistance rates of cefepime and piperacillin/tazobactam showed a statistically significant difference ( < 0.05) between strains with (+) and (-) ( < 0.05). Notably, out of the 7 individuals who died, 4 had extensively drug-resistant (57.14%).
DISCUSSION
The detection rates of various resistance and virulence genes were high, and the coexistence phenomenon was serious. In clinical practice, antibiotics should be used reasonably based on different drug resistance genes to ensure the rationality and safety of patient medication.
PubMed: 37901827
DOI: 10.3389/fmicb.2023.1280012 -
Frontiers in Pediatrics 2023This study aimed to analyze the clinical course of a newborn with congenital scrub typhus caused by vertical transmission and explore early diagnosis and treatment...
BACKGROUND
This study aimed to analyze the clinical course of a newborn with congenital scrub typhus caused by vertical transmission and explore early diagnosis and treatment strategies. The clinical data of the neonate were retrospectively analyzed and the related literature was reviewed.
CASE PRESENTATION
The newborn was a full-term one, with a good Apgar score at birth. The neonate had apnea at 3 h of life, requiring NICU care and IV antibiotics (piperacillin) for suspected sepsis. An examination revealed hepatosplenomegaly. Blood tests revealed anemia and thrombocytopenia and a chest x-ray showed patchy inflammation. On the second day of life, he developed a fever. On the third day of life, he required mechanical ventilation because his condition worsened after he presented with dyspnea, hypotension, depressed sensorium, and other signs of sepsis. Importantly, the neonate's mother had a history of scrub typhus at 31 weeks of gestation. While the blood culture result was still pending, high-throughput sequencing of blood and cerebrospinal fluid was performed. To address the suspected scrub typhus infection, oral azithromycin dry suspension was added to the treatment regimen. High-throughput sequencing results on the 5th day of life confirmed a significant presence of 16SrRNA sequences in the blood, suggesting an infection. The neonate steadily recovered and was discharged 16 days after hospitalization. The neonate was followed up for 9 months, and the outcome was favorable with normal growth and development.
CONCLUSIONS
This article reports a case of congenital infection, a rare condition caused by vertical transmission. Our review of the literature, combined with the presented case, brings the total number of documented congenital scrub typhus cases caused by vertical transmission to eight. Regrettably, one patient from this group unexpectedly died on the 10th day of hospitalization, resulting in a mortality rate of 12.5% (1/8). The special transmission mode and clinical manifestations of this disease will serve as an alert to doctors for timely diagnosis and treatment. Because of the non-specific clinical manifestations of congenital scrub typhus, limited understanding, low index of suspicion among clinicians, and a lack of diagnostic facilities, scrub typhus is seriously underdiagnosed in pregnant women, fetuses, and neonates.
PubMed: 38054188
DOI: 10.3389/fped.2023.1251746