Microbiological Eradication Research Articles

Assessing the therapeutic efficacy of Cefoperazone Sodium and Sulbactam Sodium in managing surgical site infections: a retrospective analysis

Surgical site infections (SSIs) pose significant challenges in surgical care, impacting patient recovery and healthcare costs. The increasing prevalence of antibiotic-resistant bacteria necessitates effective antimicrobial strategies. This study assesses the therapeutic efficacy and safety of Cefoperazone Sodium and Sulbactam Sodium in managing SSIs and compares its effectiveness against a standard treatment. A retrospective analysis was conducted on 110 patients with clinically and microbiologically confirmed SSIs from December 2020 to December 2023. Patients were divided into two groups: 55 received Cefoperazone Sodium and Sulbactam Sodium, while 55 were treated with Cefuroxime. The efficacy was evaluated based on microbiological eradication and clinical improvement, assessed after 3 days of treatment. Statistical analyses were performed using SPSS version 27.0, with significance set at p < 0.05. Demographic and clinical characteristics showed no significant differences between groups, ensuring comparability. The observation group demonstrated a cure rate of 58.18% and an overall efficacy rate of 94.55%. In contrast, the control group showed a cure rate of 32.73% and an overall efficacy rate of 70.91%. Statistical analysis revealed a significant difference in therapeutic success between the groups (Chi-square value of 9.16, p-value < 0.05). The combination of Cefoperazone Sodium and Sulbactam Sodium could provide a more effective option for managing SSIs, potentially improving cure rates and overall treatment outcomes compared to Cefuroxime.

Effectiveness and Nephrotoxicity of Polymyxin B among Intensive Care Unit Patients: A Clinical Evaluation

Polymyxin B is a reserve antibiotic, but there has been an upsurge in its use due to a rise in multidrug-resistant gram-negative bacteria. However, nephrotoxicity and resistance concerns persist, with global resistance rates reaching 29%. Effectiveness of Polymyxin B (clinical and microbiological response) and the frequency of nephrotoxicity is not well documented in resource limited settings. Research is essential to guide optimization of Polymyxin B therapy and inform the adoption of measures for early detection of kidney injury to prevent damage. This study aimed to assess the effectiveness of Polymyxin B by evaluating clinical and microbiological responses and determining nephrotoxicity incidence using KDIGO criteria in ICU patients at Moi Teaching and Referral Hospital (MTRH). A prospective observational cohort study was conducted at MTRH ICUs between December 2021 and November 2022, on patients treated with Polymyxin B. Data on demographics, comorbidities, Polymyxin B dosage regimens, clinical responses, and microbiological results were collected. Descriptive statistics summarized patient characteristics, while associations between dosage regimens and outcomes were evaluated using Fisher's exact test and multivariate regression, with a p&lt;0.05 considered statistically significant. Forty-four patients with a mean age of 48 years were included; 66% were male, and cerebrovascular disease was the most common comorbidity. All patients had multidrug-resistant gram-negative infections qualifying for Polymyxin B therapy. Most (89%) received monotherapy, with 86% achieving a good clinical response, 7% experiencing treatment failure, and 7% dying. Doses of 20,000–25,000 IU/Kg/day were associated with microbiological eradication and good clinical response (p&lt;0.001), while 15,000 IU/Kg/day was associated with treatment failure. Acute kidney injury occurred in 48% of patients, with 68% developing hypomagnesemia. Polymyxin B at doses of between 20,000-25,000IU/Kg/day should be considered as a starting dose due to the association with good clinical response, with alternate-day monitoring of serum creatinine levels for early detection of nephrotoxicity.

UROPOT: study protocol for a randomized, double-blind phase I/II trial for metabolism-based potentiation of antimicrobial prophylaxis in the urological tract

BackgroundUrinary tract catheters, including Double-J or ureteral stents, are prone to bacterial colonization forming biofilms and leading to asymptomatic bacteriuria. In the context of asymptomatic bacteriuria, endourological procedures causing mucosa-inducing lesions can lead to severe infections. Antibiotic prophylaxis is warranted, yet its efficacy is limited by biofilm formation on stents. Biofilms promote antibiotic tolerance, the capacity of genetically susceptible bacteria to survive a normally lethal dose of antimicrobial therapy. The UROPOT study evaluates the effectiveness of a first-in-type metabolism-based aminoglycoside potentiation for (i) preventing infectious complications of asymptomatic bacteriuria during mucosa lesion-inducing endourological procedures and (ii) assessing its anti-tolerance efficacy.MethodsThe UROPOT trial is a phase I/II single-center (Lausanne University Hospital (CHUV), Switzerland) randomized double-blinded trial. Over 2 years, patients with asymptomatic Escherichia coli and/or Klebsiella pneumoniae bacteriuria, undergoing endourological procedures, will be randomly allocated to one of three treatment arms (1:1:1 randomization ratio, 30 patients per group) to evaluate the efficacy of mannitol-potentiated low-dose amikacin compared to established standard treatments (ceftriaxone or amikacin standard dose). Patients will be recruited at the CHUV Urology Outpatient Clinic. The primary outcome is the comparative incidence of postoperative urinary tract infections (assessed at 48 h) between the investigational amikacin/mannitol therapy and standard (ceftriaxone or amikacin) antibiotic prophylaxis, defined by specific systemic symptoms and/or positive blood and/or urine culture. Secondary outcomes include assessing microbiological eradication through anti-biofilm activity, sustained microbiological eradication, and mannitol and antibiotics pharmacokinetics in blood and urine. Safety outcomes will evaluate the incidence of adverse events following amikacin/mannitol therapy and postoperative surgical complications at postoperative day 14.DiscussionUROPOT tests a novel antimicrobial strategy based on “metabolic potentiation” for prophylaxis enabling aminoglycoside dose reduction and targeting biofilm activity. The anti-biofilm effect may prove beneficial, particularly in patients who have a permanent stent in situ needing recurrent endourological manipulations strategies in preventing infections and achieving sustained microbiological eradication in pre-stented patients.Trial registrationThe protocol is approved by the local ethics committee (CER-VD, 2023–01369, protocole 2.0) and the Swiss Agency for Therapeutic Products (Swissmedic, 701,676) and is registered on the NIH’s ClinicalTrials.gov (trial registration number: NCT05761405). Registered on March 07, 2023.

Efficacy of fosfomycin-containing regimens in treating severe infections caused by KPC-producing Klebsiella pneumoniae and carbapenem-resistant Acinetobacter baumannii in critically ill patients

IntroductionFosfomycin (FOS) is gaining increasing importance as part of combination therapy for the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) and KPC-producing Klebsiella pneumoniae (KPC-Kp) thanks to its in-vitro synergism with several antibiotics, high tissue distribution and good tolerability.We analyzed the effect on 30-day survival of FOS-containing regimens compared to NO-FOS in critically ill patients admitted to intensive care unit with CRAB or KPC-Kp infections. Secondary objectives were to evaluate clinical cure and microbiologic eradication of FOS versus NO-FOS group. Materials/methodsMonocentric retrospective observational study including SARS-Cov2-negative critically ill patients with KPC-Kp or CRAB infection treated with combination antibiotic therapy with or without FOS for ≥48h (FOS vs NO-FOS groups). Primary outcome was 30-d mortality, secondary outcomes clinical cure and microbiological eradication. ResultsOf the 78 patients analyzed, 26 (33.3%) were men, median (IQR) age and Charlson Comorbidity Index (CCI) were 67 years (53-74) and 4 (2-5), respectively. Septic shock was present in 18 patients (23.1%), 37 (47.4%) were CRAB, 41 (52.6%) KPC-Kp. Compared to NO-FOS, patients receiving FOS had higher clinical cure (89.2%vs65.9%, p=0.017), early (<72h) improvement (78.4%vs52.2%, p=0.018), microbiological eradication (87.5%vs62.2%, p=0.027) and lower 7-, 14- and 30-d mortality (0%vs4.6%, p=0.027, 2.7%vs22%, p=0.016, 13.5%vs34.2%, p=0.039, respectively). This effect was particularly evident for infections sustained by KPC-Kp. At multivariate analysis, receiving FOS was independently associated with survival (HR 0.29, IC95% 0.09-0.93, p=0.038), confirmed after IPTW (HR 0.501 IC95% 0.25-0.98 p=0.042). ConclusionsFOS-containing regimens exhibit higher clinical cure, higher microbiological eradication and reduced mortality than NO FOS-containing regimens in critically ill patients with CRAB and KPC-Kp infections.

Efficacy and safety of vancomycin compared with those of alternative treatments for methicillin-resistant Staphylococcus aureus infections: An umbrella review.

To summarize the evidence on the efficacy and safety of vancomycin compared with those of alternative treatments in adult patients with methicillin-resistant Staphylococcus aureus (MRSA) infection. PubMed, Embase, and Web of Science were searched up to December 15, 2023, for systematic reviews and meta-analyses comparing vancomycin with alternative MRSA treatments. Primary outcomes included clinical cure and microbiological eradication rates. Organ-specific safety outcomes were assessed. Summary estimates were recalculated using a random-effects model. Evidence was graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool. This study was registered in PROSPERO (CRD42022340359). This umbrella review included 19 studies and 71 meta-analyses (46 efficacy and 25 safety) comparing vancomycin with 10 alternative treatments across different MRSA infection types and populations. GRADE assessment showed that 29.58% of the meta-analyses were of high quality. Linezolid and daptomycin showed higher efficacy in MRSA-induced skin and soft tissue infections and pneumonia (moderate evidence quality) and bacteremia (very low evidence quality), respectively, compared with that of vancomycin. Cephalosporins had a higher risk of nausea, whereas linezolid had a higher risk of nausea, diarrhea, and thrombocytopenia than that of vancomycin. Vancomycin posed a higher risk of rash, pruritus, red man syndrome, and nephrotoxicity than that of alternatives. The quality of evidence supporting the higher efficacy of alternative treatment over vancomycin for MRSA infection was not high. Given varying safety profiles and advancements in therapeutic monitoring, careful consideration of patient-specific factors and pharmacokinetics is crucial when selecting treatment alternatives to vancomycin.

Efficacy of Ciprofloxacin in Treating Gram-Negative Infections: Does Obesity Matter?

Obesity is considered a health issue associated with increased morbidity and a risk factor for multiple conditions, such as type 2 diabetes, cardiovascular diseases and infections. It may affect the pharmacokinetics and pharmacodynamics of many drugs, including antimicrobials like ciprofloxacin. Regrettably, data on ciprofloxacin's efficacy in obese patients remain scarce. This study aims to evaluate the impact of obesity on the efficacy of ciprofloxacin in treating Gram-negative bacterial infections. A retrospective multicenter cohort study was conducted in two tertiary hospitals in Saudi Arabia. Adult patients (≥18 years) treated with ciprofloxacin for confirmed Gram-negative infection between January 2017 and April 2023 were included. Patients were excluded if they received ciprofloxacin empirically, had inadequate source control within 72 h, or had missing weight and height information at ciprofloxacin initiation. The primary outcome was clinical cure, defined as the resolution of the clinical infection manifestations without additional therapeutic management by the end of treatment. Other secondary and safety outcomes were also assessed. A total of 99 patients were included, divided into obese (n = 42) and non-obese (n = 57) groups. The obese group had a significantly lower median age (50 years) compared to the non-obese group (64 years) (p = 0.002). The obese group had fewer male patients (38.10% vs. 68.42%; p = 0.004), higher body weight (90 (81-97) vs. 63 (55-70) days; p < 0.001), and lower height (158 (155-165) vs. 165 (158-172) days; p = 0.008) compared to non-obese. Urinary tract infection was the most common type, with Escherichia coli being the most common isolate. The median hospital length of stay was shorter in the obese group than in the non-obese group (1 vs. 3 days, p = 0.007). There were no significant differences in clinical cure rates between obese (85.71%) and non-obese (85.96%) patients (p = 1). No significant differences were observed in terms of in-hospital mortality, 30-day mortality, or 60-day infection recurrence rates between the two groups. Microbiological eradication was not achieved in the obese group, whereas a 10.53% eradication rate was observed in the non-obese group (p = 0.037). However, the majority of the patients had indeterminate eradication. The incidence of adverse drug reactions (ADRs) was lower in the obese group (4.76%) compared to the non-obese group (17.54%, p = 0.066). Treatment with ciprofloxacin in obese patients has similar efficacy and safety outcomes compared to non-obese patients with infections due to Gram-negative pathogens.

Retrospective analysis of molecular characteristics, risk factors, and outcomes in carbapenem-resistant Klebsiella pneumoniae bloodstream infections

BackgroundKlebsiella pneumoniae (KP) is the second most prevalent Gram-negative bacterium causing bloodstream infections (BSIs). In recent years, the management of BSIs caused by KP has become increasingly complex due to the emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP). Although numerous studies have explored the risk factors for the development of CRKP-BSIs, the mortality of patients with KP-BSIs, and the molecular epidemiological characteristics of CRKP, the variability in data across different populations, countries, and hospitals has led to inconsistent conclusions. In this single-center retrospective observational study, we utilized logistic regression analyses to identify independent risk factors for CRKP-BSIs and factors associated with mortality in KP-BSI patients. Furthermore, a risk factor-based prediction model was developed. CRKP isolates underwent whole-genome sequencing (WGS), followed by an evaluation of microbiological characteristics, including antimicrobial resistance and virulence genes, as well as epidemiological characteristics and phylogenetic analysis.ResultsOur study included a total of 134 patients with KP-BSIs, comprising 50 individuals infected with CRKP and 84 with carbapenem-susceptible Klebsiella pneumoniae (CSKP). The independent risk factors for CRKP-BSIs were identified as gastric catheterization (OR = 9.143; CI = 1.357–61.618; P = 0.023), prior ICU hospitalization (OR = 4.642; CI = 1.312–16.422; P = 0.017), and detection of CRKP in non-blood sites (OR = 8.112; CI = 2.130-30.894; P = 0.002). Multivariate analysis revealed that microbiologic eradication after 6 days (OR = 3.569; CI = 1.119–11.387; P = 0.032), high Pitt bacteremia score (OR = 1.609; CI = 1.226–2.111; P = 0.001), and inappropriate empirical treatment after BSIs (OR = 6.756; CI = 1.922–23.753; P = 0.003) were independent risk factors for the 28-day mortality in KP-BSIs. The prediction model confirmed that microbiologic eradication after 6.5 days and a Pitt bacteremia score of 4.5 or higher were significant predictors of the 28-day mortality. Bioinformatics analysis identified ST11 as the predominant CRKP sequence type, with blaKPC−2 as the most prevalent gene variant. CRKP stains carried multiple plasmid-mediated resistance genes along with some virulence genes. Phylogenetic analysis indicated the presence of nosocomial transmission of ST11 CRKP within the ICU.ConclusionsThe analysis of risk factors for developing CRKP-BSIs and the association between KP-BSIs and 28-day mortality, along with the development of a risk factor-based prediction model and the characterization of CRKP strains, enhances clinicians’ understanding of the pathogens responsible for BSIs. This understanding may help in the timely administration of antibiotic therapy for patients with suspected KP-BSIs, potentially improving outcomes.

Association between Extended Meropenem Regimen and Achievement of Aggressive PK/PD in Patients Receiving Continuous Renal Replacement Therapy for Septic AKI.

Aggressive pharmacokinetic (PK)/pharmacodynamic (PD) targets have shown better microbiological eradication rates and a lower propensity to develop resistant strains than conservative targets. We investigated whether meropenem blood levels, including aggressive PK/PD, were acceptable in terms of efficacy and safety using a meropenem regimen of 1 g infusion every 8 h over 3 h in patients undergoing continuous renal replacement therapy (CRRT) for septic acute kidney injury (AKI). Aggressive PK/PD targets were defined as the percentage of time that the free concentration (%fT) > 4 × minimal inhibitory concentration (MIC), the toxicity threshold was defined as a trough concentration >45 mg/L, and the percentage of achievement at each MIC was evaluated. The 100% fT > 4 × MIC for a pathogen with an MIC of 0.5 mg/L was 89%, and that for a pathogen with an MIC of 2 mg/L was 56%. The mean steady-state trough concentration of meropenem was 11.9 ± 9.0 mg/L and the maximum steady-state trough concentration was 29.2 mg/L. Simulations using Bayesian estimation showed the probability of achieving 100% fT > 4 × MIC for up to an MIC of 2 mg/L for the administered administration via continuous infusion at 3 g/24 h. We found that an aggressive PK/PD could be achieved up to an MIC of 0.5 mg/L with a meropenem regimen of 1 g infused every 8 h over 3 h for patients receiving CRRT for septic AKI. In addition, the risk of reaching the toxicity range with this regimen is low. In addition, if the MIC was 1-2 mg/L, the simulation results indicated that aggressive PK/PD can be achieved by continuous infusion at 3 g/24 h without increasing the daily dose.

A randomized non-inferiority study comparing imipenem/cilastatin/relebactam with standard-of-care Gram-negative coverage in cancer patients with febrile neutropenia.

Antibiotic overuse leads to the emergence of antibiotic resistance that threatens immunocompromised cancer patients. Infections caused by MDR Gram-negative pathogens are difficult to treat and associated with high mortality. Hence, empirical therapy with standard-of-care (SOC) antibiotics could be suboptimal in these vulnerable patients. New antibiotics covering potential resistant pathogens may be considered. We conducted a randomized non-inferiority study comparing safety and efficacy of imipenem/cilastatin/relebactam (IPM/REL), a β-lactam/β-lactamase inhibitor combination, with SOC antibiotics (cefepime, piperacillin/tazobactam or meropenem) in cancer patients with febrile neutropenia. Patients received at least 48 h of IV antibiotics and were assessed at end-of-IV (EOIV) therapy, test of cure (TOC; Days 21-28), and late follow-up (LFU; Days 35-42). A total of 100 patients were enrolled (49 IPM/REL and 50 SOC). Demographics and rates of documented microbiological infections were similar in both groups. In the SOC arm, 86% of antibiotics consisted of cefepime. Patients on IPM/REL had a higher favourable clinical response at EOIV than those on SOC (90% versus 74%; P = 0.042); however, responses were similar at TOC and LFU. Microbiological eradication was comparable at all three timepoints. Study drug-related adverse events and adverse events leading to drug discontinuation were similar in both groups, with no study drug-related mortality. Our results suggest that compared with SOC antibiotics, predominantly cefepime, IPM/REL for empirical coverage of febrile neutropenia in cancer patients is generally safe and could be associated with a better clinical outcome at EOIV. The current SOC consisting mainly of agents that do not cover for ESBL-producing and carbapenem-resistant Enterobacterales bacteria should be reconsidered.

Predictive Value of Vancomycin AUC24/MIC Ratio for 30-day Mortality in Patients with Severe or Complicated Methicillin-Resistant Staphylococcus aureus Infections: A Multicenter Retrospective Study.

Although vancomycin is typically employed against methicillin-resistant Staphylococcus aureus (MRSA) infections, the optimal ratio of 24-h area under the concentration-time curve to minimum inhibitory concentration (AUC24/MIC) for severe or complicated infections lacks clear guideline recommendations. This study aimed to determine the target AUC24/MIC ratio associated with treatment outcomes of infections treated with vancomycin. This retrospective multicenter cohort study included adult patients receiving ≥ 5days of vancomycin for severe/complicated MRSA infections (e.g., osteoarticular, pulmonary, endocarditis, etc.) between January 2018 and December 2023. The primary outcome was 30-day mortality, with secondary outcomes including clinical success, microbiological eradication, and nephrotoxicity. Receiver operating characteristic (ROC) curve analysis was used to identify the AUC24/MIC cutoff for 30-day mortality. Multivariate regression analysis was used to determine association between AUC24/MIC and outcomes. This study included 82 patients. ROC identified a target AUC24/MIC of ≥ 505 for 30-day mortality. The overall 30-day mortality rate (22.0%) was significantly higher for below average AUC24/MIC cutoff (34.1%) than for above AUC24/MIC cutoff group (9.8%). Multivariate analysis confirmed AUC24/MIC of < 505 as an independent predictor (adjusted odds ratio, 5.001; 95% confidence interval, 1.335-18.75). The clinical success rate differed significantly between below- and above-cutoff groups, whereas microbiological eradication tended to favor the above-cutoff group. The nephrotoxicity rates were comparable between groups. In treating severe/complicated MRSA infections, vancomycin AUC24/MIC ratio ≥ 505 was independently associated with favorable 30-day mortality. Given the retrospective nature of this study, further prospective studies are essential to confirm the reliability of the target AUC24/MIC ratios.

Patterns of Antibiotic Resistance in Urinary Tract Infections: A Retrospective Observational Study.

Urinary tract infections (UTIs) are among the most common bacterial infections, and antibiotic resistance complicates empiric treatment. This study aimed to describe recent resistance patterns among uropathogens in a tertiary-care teaching hospital to optimize empiric UTI management. This retrospective observational study included 280 patients diagnosed with UTIs at the Dr. Patnam Mahender Reddy Institute of Medical Sciences, Hyderabad, over a six-month period from June 2023 to November 2023. Urine culture and antibiotic susceptibility data were collected from electronic medical records. Patient demographics, including age, sex, and comorbid diabetes, were recorded. Causative uropathogens and their resistance rates to commonly prescribed UTI antibiotics were analyzed. Empiric antibiotic treatment patterns and outcomes were talked about. These included clinical cure, recurrence, susceptibility match, and microbiologic eradication. The mean age of patients was 43.5 years, with 196 (70%) being female and 70 (25%) having diabetes. Escherichia coli caused 210 (75%) of UTIs, Klebsiella pneumoniae 42 (15%), Proteus mirabilis 14 (5%), Enterococcus faecalis 8 (3%), and Staphylococcus saprophyticus 6 (2%). E. coli resistance rates were 48% for ampicillin, 25% for ciprofloxacin, 18% for trimethoprim/sulfamethoxazole (TMP/SMX), and 5% for nitrofurantoin. K. pneumoniae resistance rates were 89% for ampicillin, 67% for ciprofloxacin, 44% for TMP/SMX, and 22% for nitrofurantoin. The most frequently prescribed antibiotic was nitrofurantoin (45%), then ciprofloxacin (35%). Clinical cure was achieved in 75% of cases. Recurrent UTIs within four weeks occurred in 25% of cases. Treatment matched urine culture susceptibility in 82% of patients. The rising fluoroquinolone resistance highlights the need for current local data to guide empiric UTI treatment. Nitrofurantoin had low resistance rates and was an effective first-line therapy. Ongoing monitoring of resistance patterns in UTIs is essential to optimize antibiotic selection.

Phage Therapy for Cardiac Implantable Electronic Devices and Vascular Grafts: A Targeted Literature Review.

Infections of cardiac implantable electronic devices (CIEDs) and vascular grafts are some of the most dreaded complications of these otherwise life-saving devices. Many of these infections are not responsive to conventional treatment, such as systemic antibiotics and surgical irrigation and debridement. Therefore, innovative strategies to prevent and manage these conditions are warranted. Among these, there is an increasing interest in phages as a therapeutical option. In this review, we aim to collect the available evidence for the clinical application of phage therapy for CIED and vascular graft infections through literature research. We found 17 studies for a total of 34 patients. Most of the indications were left ventricular assist device (LVAD) (n = 20) and vascular graft infections (n = 7). The bacteria most often encountered were Staphylococcus aureus (n = 18) and Pseudomonas aeruginosa (n = 16). Clinical improvements were observed in 21/34 (61.8%) patients, with microbiological eradication in 18/21 (85.7%) of them. In eight cases, an adverse event related to phage therapy was reported. Phage therapy is a promising option for difficult-to-treat CIED and vascular graft infections by means of an individualized approach. Clinical trials and expanded access programs for compassionate use are needed to further unveil the role of phage therapy in clinical application.

Ceftazidime-avibactam combination therapy versus monotherapy for treating carbapenem-resistant gram-negative infection: a systemic review and meta-analysis.

This meta-analysis was conducted to compare the efficacy of ceftazidime-avibactam combination therapy with that of monotherapy in the treatment of carbapenem-resistant Gram-negative bacterial (CR-GNB). A literature search of PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov was conducted until September 1, 2023. Only studies that compared CZA combination therapy with monotherapy for CR-GNB infections were included. A total of 25 studies (23 retrospective observational studies and 2 prospective studies) involving 2676 patients were included. There was no significant difference in 30-day mortality between the study group receiving combination therapy and the control group receiving monotherapy (risk ratio [RR] 0.91; 95% confidence interval [CI] 0.71-1.18). In addition, no significant differences were observed between the study and the control group in terms of in-hospital mortality (RR 1.00; 95% CI 0.79-1.27), 14-day mortality (RR 1.54; 95% CI 0.24-9.91), 90-day mortality (RR 1.18; 95% CI 0.62-2.22), and clinical cure rate (RR 0.95; 95% CI 0.84-1.08). However, the combination group had a borderline higher microbiological eradication rate than the control group (RR 1.15; 95% CI 1.00-1.32). Compared to monotherapy, CZA combination therapy did not yield additional clinical benefits. However, combination therapy may be associated with favorable microbiological outcomes.

Efficacy of adjunctive inhaled colistin and tobramycin for ventilator-associated pneumonia: systematic review and meta-analysis

IntroductionVentilator-associated pneumonia (VAP) presents a significant challenge in intensive care units (ICUs). Nebulized antibiotics, particularly colistin and tobramycin, are commonly prescribed for VAP patients. However, the appropriateness of using inhaled antibiotics for VAP remains a subject of debate among experts. This study aims to provide updated insights on the efficacy of adjunctive inhaled colistin and tobramycin through a comprehensive systematic review and meta-analysis.MethodsA thorough search was conducted in MEDLINE, EMBASE, LILACS, COCHRANE Central, and clinical trials databases (www.clinicaltrials.gov) from inception to June 2023. Randomized controlled trials (RCTs) meeting specific inclusion criteria were selected for analysis. These criteria included mechanically ventilated patients diagnosed with VAP, intervention with inhaled Colistin and Tobramycin compared to intravenous antibiotics, and reported outcomes such as clinical cure, microbiological eradication, mortality, or adverse events.ResultsThe initial search yielded 106 records, from which only seven RCTs fulfilled the predefined inclusion criteria. The meta-analysis revealed a higher likelihood of achieving both clinical and microbiological cure in the groups receiving tobramycin or colistin compared to the control group. The relative risk (RR) for clinical cure was 1.23 (95% CI: 1.04, 1.45), and for microbiological cure, it was 1.64 (95% CI: 1.31, 2.06). However, there were no significant differences in mortality or the probability of adverse events between the groups.ConclusionAdjunctive inhaled tobramycin or colistin may have a positive impact on the clinical and microbiological cure rates of VAP. However, the overall quality of evidence is low, indicating a high level of uncertainty. These findings underscore the need for further rigorous and well-designed studies to enhance the quality of evidence and provide more robust guidance for clinical decision-making in the management of VAP.

Efficacy and safety of generic cefoperazone/sulbactam versus branded cefoperazone/sulbactam in the treatment of bacterial infections: a systematic review and meta-analysis

This study aim to assess the clinical efficacy and safety of generic cefoperazone/sulbactam compared to the branded cefoperazone/sulbactam (Sulperazon) in treating bacterial infections through a meta-analysis. Searches were conducted across PubMed, Embase, Cochrane Library, CNKI, WanFang, VIP databases, and Clinical Trials database, resulting in the inclusion of 11 studies comprising 7 randomized controlled trials (RCTs) and 4 retrospective cohort studies (RCSs). Meta-analysis of the RCTs indicated no statistical differences in clinical success rates, clinical cure rates, microbiological eradication rates, and incidence of adverse reactions between the generic cefoperazone/sulbactam and the branded version. Findings from the RCSs aligned with those from the RCTs, demonstrating that generic versions of cefoperazone/sulbactam are equivalent in efficacy and safety to their branded counterparts in treating bacterial infections.

Comparative Impact of an Optimized PK/PD Target Attainment of Piperacillin-Tazobactam vs. Meropenem on the Trend over Time of SOFA Score and Inflammatory Biomarkers in Critically Ill Patients Receiving Continuous Infusion Monotherapy for Treating Documented Gram-Negative BSIs and/or VAP.

(1) Background: The advantage of using carbapenems over beta-lactam/beta-lactamase inhibitor combinations in critically ill septic patients still remains a debated issue. We aimed to assess the comparative impact of an optimized pharmacokinetic/pharmacodynamic (PK/PD) target attainment of piperacillin-tazobactam vs. meropenem on the trend over time of both Sequential Organ Failure Assessment (SOFA) score and inflammatory biomarkers in critically ill patients receiving continuous infusion (CI) monotherapy with piperacillin-tazobactam or meropenem for treating documented Gram-negative bloodstream infections (BSI) and/or ventilator-associated pneumonia (VAP). (2) Methods: We performed a retrospective observational study comparing critically ill patients receiving targeted treatment with CI meropenem monotherapy for documented Gram-negative BSIs or VAP with a historical cohort of critical patients receiving CI piperacillin-tazobactam monotherapy. Patients included in the two groups were admitted to the general and post-transplant intensive care unit in the period July 2021-September 2023 and fulfilled the same inclusion criteria. The delta values of the SOFA score between the baseline of meropenem or piperacillin-tazobactam treatment and those at 48-h (delta 48-h SOFA score) or at 7-days (delta 7-days SOFA) were selected as primary outcomes. Delta 48-h and 7-days C-reactive protein (CRP) and procalcitonin (PCT), microbiological eradication, resistance occurrence, clinical cure, multi-drug resistant colonization at 90-day, ICU, and 30-day mortality rate were selected as secondary outcomes. Univariate analysis comparing primary and secondary outcomes between critically ill patients receiving CI monotherapy with piperacillin-tazobactam vs. meropenem was carried out. (3) Results: Overall, 32 critically ill patients receiving CI meropenem monotherapy were compared with a historical cohort of 43 cases receiving CI piperacillin-tazobactam monotherapy. No significant differences in terms of demographics and clinical features emerged at baseline between the two groups. Optimal PK/PD target was attained in 83.7% and 100.0% of patients receiving piperacillin-tazobactam and meropenem, respectively. No significant differences were observed between groups in terms of median values of delta 48-h SOFA (0 points vs. 1 point; p = 0.89) and median delta 7-days SOFA (2 points vs. 1 point; p = 0.43). Similarly, no significant differences were found between patients receiving piperacillin-tazobactam vs. meropenem for any of the secondary outcomes. (4) Conclusion: Our findings may support the contention that in critically ill patients with documented Gram-negative BSIs and/or VAP, the decreases in the SOFA score and in the inflammatory biomarkers serum levels achievable with CI piperacillin-tazobactam monotherapy at 48-h and at 7-days may be of similar extent and as effective as to those achievable with CI meropenem monotherapy provided that optimization on real-time by means of a TDM-based expert clinical pharmacological advice program is granted.

Intraventricular or intrathecal polymyxin B for treatment of post-neurosurgical intracranial infection caused by carbapenem-resistant gram-negative bacteria: a 8-year retrospective study.

Post-neurosurgical intracranial infection caused by carbapenem-resistant gram-negative bacteria (CRGNB) is a life-threatening complication. This study aimed to assess the current practices and clinical outcomes of intravenous (IV) combined with intraventricular (IVT)/intrathecal (ITH) polymyxin B in treating CRGNB intracranial infection. A retrospective study was conducted on patients with post-neurosurgical intracranial infection due to CRGNB from January 2013 to December 2020. Clinical characteristics and treatment outcomes were collected and described. Kaplan-Meier survival and multivariate logistic regression analyses were performed. The study included 114 patients, of which 72 received systemic antimicrobial therapy combined with IVT/ITH polymyxin B, and 42 received IV administration alone. Most infections were caused by carbapenem-resistant Acinetobacter baumannii (CRAB, 63.2%), followed by carbapenem-resistant Klebsiella pneumoniae (CRKP, 31.6%). Compared with the IV group, the IVT/ITH group had a higher cerebrospinal fluid (CSF) sterilization rate in 7 days (p < 0.001) and lower 30-day mortality (p = 0.032). In the IVT/ITH group, patients with CRKP infection had a higher initial fever (p = 0.014), higher incidence of bloodstream infection (p = 0.040), lower CSF sterilization in 7 days (p < 0.001), and higher 30-day mortality (p = 0.005) than those with CRAB infection. Multivariate logistic regression analysis revealed that the duration of IVT/ITH polymyxin B (p = 0.021) was independently associated with 30-day mortality. Intravenous combined with IVT/ITH polymyxin B increased CSF microbiological eradication and improved clinical outcomes. CRKP intracranial infections may lead to more difficult treatment and thus warrant attention and further optimized treatment.

The pharmacokinetics/pharmacodynamics of ceftazidime/avibactam for central nervous system infections caused by carbapenem-resistant Gram-negatives: a prospective study.

To describe the pharmacokinetics/pharmacodynamics (PK/PD) of ceftazidime/avibactam in critically ill patients with CNS infections. A prospective study of critically ill patients with CNS infections who were treated with ceftazidime/avibactam and the steady-state concentration (Css) of ceftazidime/avibactam in serum and/or CSF was conducted between August 2020 and May 2023. The relationship between PK/PD goal achievement, microbial eradication and the clinical efficacy of ceftazidime/avibactam was evaluated. Seven patients were finally included. The ceftazidime/avibactam target attainment in plasma was optimal for three, quasi-optimal for one and suboptimal for three. In three patients with CSF drug concentrations measured, ceftazidime/avibactam target attainment in CSF was 100% (3/3), which was optimal. The AUCCSF/serum values were 0.59, 0.44 and 0.35 for ceftazidime and 0.57, 0.53 and 0.51 for avibactam. Of the seven patients, 100% (7/7) were treated effectively, 71.4% (5/7) achieved microbiological eradication, 85.7% (6/7) survived and 14.3% (1/7) did not survive. The limited clinical data suggest that ceftazidime/avibactam is effective in the treatment of CNS infections caused by MDR Gram-negative bacilli (MDR-GNB), can achieve the ideal drug concentration of CSF, and has good blood-brain barrier penetration.

Extended Infusion of Beta-Lactams and Glycopeptides: A New Era in Pediatric Care? A Systematic Review and Meta-Analysis.

Optimizing antibiotic therapy is imperative with rising bacterial resistance and high infection mortality. Extended infusion defined as a continuous infusion (COI) or prolonged infusion (PI) of beta-lactams and glycopeptides might improve efficacy and safety compared to their intermittent administration (IA). This study aimed to evaluate the efficacy and safety of extended infusion in pediatric patients. Adhering to Cochrane standards, we conducted a systematic review with meta-analysis investigating the efficacy and safety of COI (24 h/d) and PI (>1 h/dose) compared to IA (≤1 h/dose) of beta-lactams and glycopeptides in pediatrics. Primary outcomes included mortality, clinical success, and microbiological eradication. Five studies could be included for the outcome mortality, investigating meropenem, piperacillin/tazobactam, cefepime, or combinations of these. The pooled relative risk estimate was 0.48 (95% CI 0.26-0.89, p = 0.02). No significant differences between the administration modes were found for the outcomes of clinical success, microbiological eradication (beta-lactams; glycopeptides), and mortality (glycopeptides). No study reported additional safety issues, e.g., adverse drug reactions when using COI/PI vs. IA. Our findings suggest that the administration of beta-lactams by extended infusion leads to a reduction in mortality for pediatric patients.

Pharmacokinetics Profile and Genetics of Double Antiviral Therapy with Remdesivir and Nirmatrelvir/Ritonavir for Prolonged COVID-19 in Patients Treated with Rituximab: A Real-Life Study and Literature Review

Introduction: Patients with hematologic malignancies are more likely to develop severe and prolonged SARS-CoV-2 infection, often showing viral persistence despite the use of authorized antivirals. Herein, we report the cases of four patients who received rituximab for different conditions and developed persistent COVID-19 treated with an extended course of dual antivirals, Nirmatrelvir/Ritonavir and Remdesivir. Moreover, we describe the pharmacokinetics and pharmacogenetics (PK/PG) characteristics of Nirmatrelvir/Ritonavir and Remdesivir treatment in two of these patients. Methods: Plasma specimens for evaluation of trough concentrations (Ctrough) were collected 10 min before the daily dose administration, in addition to 3 h (Cmax), 4 h (C4h), 6 h (C6h) and 1 h (Cmax) after the administration of Nirmatrelvir/Ritonavir and Remdesivir, respectively. The following gene single-nucleotide polymorphisms (SNPs) were investigated: ABCB1 3435 (rs1045642) C &gt; T, ABCB1 1236 (rs1128503) C &gt; T, PXR 63396 (rs2472667) T &gt; C, CYP2D6 (rs1135840) G &gt; C, and CYP3A4*1B (rs2740574) G &gt; A. Results: Double antiviral treatment was successful in terms of symptoms resolution, whereas three out of four patients achieved microbiological eradication. Based on our results, concentrations of Nirmatrelvir ranging from 50 to 5000 ng/mL were effective, whereas a higher concentration (range 1068–3377 ng/mL), compared to that previously reported in patients with similar weight and BMI, was evidenced for Ritonavir. Considering the genetic variant analysis, ABCB1 3435 CT and 1236 CT genotypes were found in patient 1; and ABCB1 3435 CC and 1236 CC in patient 2. In conclusion, this real-life study supports the usefulness of TDM and genetics in immunocompromised patients with persistent SARS-CoV-2 infection, a challenging setting for clinicians in which personalized medicine may improve outcome.