Frequency of drug-resistant bacterial isolates among pregnant women with UTI in maternity and children's hospital, Bisha, Saudi Arabia.

Urinary tract infections (UTIs) are one of the most prevalent bacterial infections affecting humans, with a higher incidence among women. Pregnant women are at an increased risk of developing UTIs, which can have detrimental consequences for both the mother and fetus. UTIs can be caused by various bacteria, and the prevalence of drug-resistant UTIs in maternity and children's hospitals is a cause for concern due to the potential for severe complications if left untreated. The primary objective of the current study was to determine the distribution of UTI-causing bacteria and investigate the antibiotic sensitivity patterns of isolated cultures obtained from pregnant women with UTIs at the Maternity and Children's Hospital, Bisha, Saudi Arabia. This cross-sectional study was conducted from October 2021 to October 2023, involving the analysis of urine samples collected from 321 participants who acquired UTIs during pregnancy. Using biochemical tests and standard cultures, the urine samples were examined for pathogenic bacteria and their anti-microbial sensitivity patterns. The study analyzed susceptibility results according to the Clinical Laboratory Standards Institute guidelines (M100, 28th Edition, 2018). Bacterial strains demonstrating resistance to three or more antibiotics were classified as multidrug-resistant (MDR). This study revealed the distribution of UTI-causing bacteria to be as follows: Escherichia coli, 57.01%; Klebsiella pneumoniae, 24.61%; Pseudomonas aeruginosa, 4.36%; Proteus mirabilis and Enterobacter cloacae, 3.74%; Streptococcus agalactiae, 3.11%; Enterococcus faecalis, 2.18%; and Staphylococcus aureus, 1.24%. Antimicrobial susceptibility testing varied among gram-positive and gram-negative bacteria. Gentamicin demonstrated the highest sensitivity among both gram-positive and gram-negative bacteria; piperacillin-tazobactam was the second most effective drug against gram-negative bacteria. The bacterial isolates showed varying susceptibility to different antibiotics, with Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa being mainly sensitive to gentamicin, piperacillin-tazobactam, and ciprofloxacin, respectively. The strategies for reducing the risk of UTIs need to be improved to limit the spread of MDR bacteria. These strategies may include promoting hygienic practices and administering appropriate antibiotics to prevent the emergence and spread of drug-resistant bacteria. Further research is required to monitor the trends in antibiotic resistance among UTI-causing bacteria and develop effective strategies for managing this public health menace.

Removal of common antimicrobial agents by sustained low-efficiency dialysis.

Adequate dosing of antimicrobials is paramount for treating infections in critically ill patients undergoing kidney replacement therapy; however, little is known about antimicrobial removal by sustained low-efficiency dialysis (SLED). The objective was to quantify the removal of cefepime, daptomycin, meropenem, piperacillin-tazobactam, and vancomycin in patients undergoing SLED. Adult patients ≥18 years with acute kidney injury (AKI) or end-stage kidney disease receiving one of the select antimicrobials and requiring SLED were included. Blood and dialysate flow rates were maintained at 250 and 100 mL/min, respectively. Simultaneous arterial and venous blood samples for the analysis of antibiotic concentrations were collected hourly for 8 hours during SLED (on-SLED). Arterial samples were collected every 2 hours for up to 6 hours while not receiving SLED (off-SLED) for the calculation of SLED clearance, half-life (t1/2) on-SLED and off-SLED, and the fraction of removal by SLED (fD). Twenty-one patients completed the study: 52% male, mean age (±SD) 53 ± 13 years, and mean weight of 98 ± 30 kg. Eighty-six percent had AKI, and 4 patients were receiving cefepime, 3 daptomycin, 10 meropenem, 6 piperacillin-tazobactam, and 13 vancomycin. The average SLED time was 7.3 ± 1.1 hours, and the mean ultrafiltration rate was 95 ± 52 mL/hour (range 10-211). The t1/2 on-SLED was substantially lower than the off-SLED t1/2 for all antimicrobials, and the SLED fD varied between 44% and 77%. An 8-hour SLED session led to significant elimination of most antimicrobials evaluated. If SLED is performed, modification of the dosing regimen is warranted to avoid subtherapeutic concentrations.

Antibiotic Treatment in Complicated Appendicitis: Can It Be Optimized?

BACKGROUND: The management of complicated appendicitis is inconclusive. Guidelines have not been established for the use of personalized antibiotic treatment. OBJECTIVES: To investigate specific risk factors to consider during the initial first-choice antibiotic therapy in children with complicated appendicitis. METHODS: This study included all pediatric patients younger than 18 years of age who underwent a laparoscopic appendectomy during 2012-2022 at a single tertiary medical center. RESULTS: In total, 300 pediatric patients underwent laparoscopic appendectomy due to complicated appendicitis. The patients were treated with ceftriaxone + metronidazole (CM). For 57 (19%) patients, the empirical treatment was changed to tazobactam/piperacillin (TP) due to resistant bacteria or clinical deterioration. The presence of generalized peritonitis during surgery and C-reactive protein (CRP) levels above 20 mg/L at admission were identified as risk factors for changing the antibiotic regimen from CM to TP. CONCLUSIONS: Generalized peritonitis and CRP > 20 gr/L were highly correlated with changing the antibiotic regimen to TP. For such patients, initial treatment with TP may result in clinical improvement and shorter hospitalization.

Antibiotic definitive treatment in ventilator associated pneumonia caused by AmpC-producing Enterobacterales in critically ill patients: a prospective multicenter observational study.

BACKGROUND: Ventilator associated pneumonia (VAP) due to wild-type AmpC-producing Enterobacterales (wtAE) is frequent in intensive care unit (ICU) patients. Despite a low level of evidence, definitive antimicrobial therapy (AMT) with third generation cephalosporins (3GCs) or piperacillin is discouraged. METHODS: Observational prospective study including consecutive wtAE VAP patients in 20 French ICUs. The primary objective was to assess the association of the choice of definitive AMT, i.e. piperacillin ± tazobactam (PTZ), 3GCs or other molecule (4GCs, carbapenems, quinolones, cotrimoxazole; control group), with treatment success at day-7. Recurrence of infection was collected as a secondary outcome, and analyzed accounting for the competing risk of death. RESULTS: From February 2021 to June 2022, 274 patients were included. Enterobacter cloacae was the most prevalent specie (31%). Seventy-eight patients (28%) had PTZ as definitive AMT while 44 (16%) had 3GCs and 152 (56%) were classified in the control group. Day-7 success rate was similar between the 3 groups (74% vs. 73% vs. 68% respectively, p = 0.814). Recurrence probability at day-28 was 31% (95% CI 21-42), 40% (95% CI 26-55) and 21% (95% CI 15-28) for PTZ, 3GCs and control groups (p = 0.020). In multivariable analysis, choice of definitive AMT was not associated with clinical success, but definitive AMT with 3GCs was associated with recurrence at day-28 [csHR(95%CI) 10.9 (1.92-61.91)]. CONCLUSION: Choice of definitive antimicrobial therapy was not associated with treatment success at day 7. However, recurrence of pneumonia at day-28 was higher in patients treated with third generation cephalosporins with no differences in mortality or mechanical ventilation duration.

Optimizing antibiotic management for patients with acute appendicitis: A quality improvement study.

BACKGROUND: To decrease surgical site infections after appendectomy for acute appendicitis, preoperative broad-spectrum antibiotics are often used in clinical practice. However, this treatment strategy has come under scrutiny because of increasing rates of antibiotic-resistant infections. METHODS: The aim of this multisite quality improvement project was to decrease the treatment of uncomplicated acute appendicitis with piperacillin-tazobactam without increasing the rate of surgical site infections. Our quality improvement intervention had 2 distinct components: (1) updating electronic health record orders to encourage preoperative administration of narrow-spectrum antibiotics and (2) educating surgeons and emergency department clinicians about selecting appropriate antibiotic therapy for acute appendicitis. Patient demographics, clinical characteristics, and outcomes were compared 6 months before and after implementation of the quality improvement intervention. RESULTS: A total of 352 laparoscopic appendectomies were performed during the 6-month preintervention period, and 369 were performed during the 6-month postintervention period. The preintervention period and postintervention period groups had similar baseline demographics, vital signs, and laboratory test values. The rate of preoperative piperacillin-tazobactam administration significantly decreased after the intervention (51.4% preintervention period vs 20.1% postintervention period, P < .001). The rate of surgical site infections was similar in both groups (superficial surgical site infections = 1.4% preintervention period vs 0.8% postintervention period, P = .50; deep surgical site infections = 1.1% preintervention period vs 0.0% postintervention period, P = .06; and organ space surgical site infections = 3.1% preintervention period vs 3.0% postintervention period, P > .99). Rates of 30-day readmission, reoperation, and Clostridioides difficile infection also did not differ between groups. CONCLUSION: Our quality improvement intervention successfully decreased piperacillin-tazobactam administration without increasing the rate of surgical site infections in patients with acute appendicitis.

Clinical recommendations for the inpatient management of lower respiratory tract infections in children and adolescents with severe neurological impairment in Germany.

Children and adolescents with severe neurological impairment (SNI) require specialized care due to their complex medical needs. In particular, these patients are often affected by severe and recurrent lower respiratory tract infections (LRTIs). These infections, including viral and bacterial etiology, pose a significant risk to these patients, often resulting in respiratory insufficiency and long-term impairments. Using expert consensus, we developed clinical recommendations on the management of LRTIs in children and adolescents with SNI. These recommendations emphasize comprehensive multidisciplinary care and antibiotic stewardship. Initial treatment should involve symptomatic care, including hydration, antipyretics, oxygen therapy, and respiratory support. In bacterial LRTIs, antibiotic therapy is initiated based on the severity of the infection, with aminopenicillin plus a beta-lactamase inhibitor recommended for community-acquired LRTIs and piperacillin-tazobactam for patients with chronic lung disease or tracheostomy. Ongoing management includes regular evaluations, adjustments to antibiotic therapy based on pathogen identification, and optimization of supportive care. Implementation of these recommendations aims to improve the diagnosis and treatment of LRTIs in children and adolescents with SNI. What is Known: • Children and adolescents with severe neurological impairment are particularly affected by severe and recurrent lower respiratory tract infections (LRTIs). • The indication and choice of antibiotic therapy for bacterial LRTI is often difficult because there are no evidence-based treatment recommendations for this heterogeneous but vulnerable patient population; the frequent overuse of broad-spectrum or reserve antibiotics in this patient population increases selection pressure for multidrug-resistant pathogens. What is New: • The proposed recommendations provide a crucial framework for focused diagnostics and treatment of LRTIs in children and adolescents with severe neurological impairment. • Along with recommendations for comprehensive and multidisciplinary therapy and antibiotic stewardship, ethical and palliative care aspects are taken into account.

Exposure levels and target attainment of piperacillin/tazobactam in adult patients admitted to the intensive care unit: a prospective observational study.

PURPOSE: The objective of this study was to evaluate the exposure and the pharmacodynamic target attainment of piperacillin/tazobactam (PTZ) in adult critically ill patients. METHODS: We conducted a prospective observational study in the intensive care unit (ICU) of the Hôpital du Sacré-Cœur de Montréal (a Level I trauma centre in Montreal, QC, Canada) between January 2021 and June 2022. We included patients aged 18 yr or older admitted to the ICU who received PTZ by intravenous administration. Demographic and clinical characteristics were collected, and clinical scores were calculated. On study day 1 of antimicrobial therapy, three blood samples were collected at the following timepoints: one hour after PTZ dose administration and at the middle and at the end of the dosing interval. The sampling schedule was repeated on days 4 and 7 of therapy if possible. Samples were analyzed by ultra-high performance liquid chromatography with diode array detector to determine the total piperacillin concentration. Middle- and end-of-interval concentrations were used for target attainment analyses, and were defined as a concentration above the minimal inhibitory concentration of 16 mg·L-1, corresponding to the breakpoint of Enterobacteriaceae and Pseudomonas aeruginosa. RESULTS: Forty-three patients were recruited and 202 blood samples were analyzed. The most prevalent dose was 3/0.375 g every six hours (n = 50/73 doses administered, 68%) with a 30-min infusion. We observed marked variability over the three sampling timepoints, and the median [interquartile range] piperacillin concentrations at peak, middle of interval, and end of interval were 109.4 [74.0-152.3], 59.3 [21.1-74.4], and 25.3 [6.8-44.6] mg·L-1, respectively. When assessing target attainment, 37% of patients did not reach the efficacy target of a trough concentration of 16 mg·L-1. The majority of patients who were underexposed were patients with normal to augmented renal clearance. CONCLUSION: In this prospective observational study of adult ICU patients receiving intravenous PTZ, a large proportion had subtherapeutic concentrations of piperacillin. This was most notable in patients with normal to augmented renal clearance. More aggressive dosage regimens may be required for this subpopulation to ensure attainment of efficacy targets.

RéSUMé: OBJECTIF: L'objectif de cette étude était d'évaluer l'exposition et l'atteinte des cibles pharmacodynamiques de la pipéracilline/tazobactam (PTZ) chez la patientèle adulte aux soins intensifs. MéTHODES: Nous avons réalisé une étude observationnelle prospective dans l'unité de soins intensifs (USI) de l'Hôpital du Sacré-Cœur de Montréal (un centre de traumatologie de niveau 1 à Montréal, QC, Canada) entre janvier 2021 et juin 2022. Nous avons inclus les patient·es adultes âgé·es de 18 ans ou plus admis·es à l'USI ayant reçu de la PTZ par administration intraveineuse. Les caractéristiques démographiques et cliniques ont été recueillies, et les scores cliniques ont été calculés. Au jour 1 de la thérapie antimicrobienne, trois échantillons sanguins ont été prélevés aux moments suivants : 1 h après l'administration de la dose de PTZ, au milieu et à la fin de l'intervalle d'administration. Le calendrier d'échantillonnage a été répété aux jours 4 et 7 de la thérapie si possible. Les échantillons ont été analysés par chromatographie liquide à ultra-haute performance avec détecteur à diodes pour déterminer la concentration totale de pipéracilline. Les concentrations du milieu et de fin d'intervalle ont été utilisées pour les analyses d'atteinte de cible, définie comme une concentration supérieure à la concentration minimale inhibitrice de 16 mg·L-1, associée aux Enterobacteriaceae et au Pseudomonas aeruginosa. RéSULTATS: Quarante-trois patient·es ont été recruté·es et 202 échantillons sanguins ont été analysés. La dose la plus prévalente était une dose de 3/0,375 g aux 6 h (n = 50/73 doses administrées, 68 %) avec une perfusion sur 30 min. Nous avons observé une variabilité marquée aux trois temps de prélèvement, et les concentrations médianes [intervalle interquartile] de pipéracilline au pic, au milieu et à la fin de l'intervalle étaient respectivement de 109,4 [74,0-152,3], 59,3 [21,1-74,4] et 25,3 [6,8-44,6] mg·L−1. Lors de l'évaluation de l'atteinte de la cible, 37 % des patient·es n'ont pas atteint la cible d'efficacité d'une concentration de 16 mg·L−1 à la fin de l'intervalle posologique. La majorité des patient·es sous-exposé·es étaient des personnes dont la clairance rénale était normale ou augmentée. CONCLUSION: Dans cette étude observationnelle prospective de patient·es adultes aux soins intensifs recevant de la PTZ par voie intraveineuse, une grande proportion de patient·es présentait des concentrations sous-thérapeutiques de pipéracilline. Ceci était plus marqué chez les patient·es ayant une clairance rénale normale ou augmentée. Des schémas posologiques plus agressifs pourraient être nécessaires pour cette sous-population afin de favoriser l'atteinte des cibles d'efficacité.

Potential benefits of therapeutic drug monitoring for beta-lactam antibiotics in augmented renal clearance patients: a case report.

Augmented renal clearance (ARC) is commonly described in critically ill patients, making drug pharmacokinetics even harder to predict in this population. This case report displays the value of therapeutic drug monitoring (TDM) of piperacillin/tazobactam (PTZ) in this population. We identified two patients with ARC and intermittent administration of PTZ who took part in a prospective, descriptive study conducted at Hôpital du Sacré-Cœur de Montréal. Both had plasma samples drawn at peak, middle, and end of their dosing intervals of PTZ. Minimal inhibitory concentrations (MICs) of 4 and 8 mg/L were chosen to evaluate therapeutic target attainment at middle and end of dosing interval. The first patient was a 52-year-old male with a renal clearance rate estimated at 147 mL/min who received 3.375 g PTZ every 6 h. The second patient, a 49-year-old male, had an estimated renal clearance rate of 163 mL/min and received the same regimen. Both patients had piperacillin concentrations above the target MICs at middle of the dosing interval, but they failed to reach a trough concentration above 8 mg/L. The present case report showcases two patients with subtherapeutic PTZ concentrations despite strict following of local administration protocols. This suboptimal administration could not only lead to treatment failure, but also to the selection and growth of resistant pathogens. Implementing TDM would offer the possibility to adjust drug regimens in real-time and prevent situations like these from occurring.

Efficacy of cefmetazole in immunocompetent patients with uncomplicated colonic diverticulitis: A propensity score matching analysis.

INTRODUCTION: The incidence of colonic diverticulitis is increasing in Japan. Although antimicrobial chemotherapy is a treatment option, Japanese guidelines for diverticulosis do not recommend any antibiotic in particular and antibiotic selection is left to the discretion of the prescribing physician, who often selects antibiotics with anti-pseudomonal activity. Therefore, this study compared the efficacy of cefmetazole (CMZ) with that of tazobactam/piperacillin (TAZ/PIPC) in hospitalized Japanese immunocompetent patients with uncomplicated colonic diverticulitis. PATIENTS AND METHODS: This retrospective study included Japanese immunocompetent patients hospitalized for colonic diverticulitis between April 2019 and March 2022. Participants were divided into the CMZ and TAZ/PIPC groups. After propensity score matching, the intergroup differences in clinical outcomes, including adverse events, mortality, and re-admission rate, were ascertained. RESULTS: During the study period, 142 Japanese patients were hospitalized with community-onset colonic diverticulitis; 124 of these patients were immunocompetent. Of the 124 patients, 42 were excluded, and the CMZ and TAZ/PIPC groups comprised 62 and 20 patients, respectively. After propensity score matching, there were 16 patients in each group. There was no significant intergroup difference in the mortality and re-admission rates; however, the incidence of liver dysfunction was significantly higher (p = 0.018) in the TAZ/PIPC group. CONCLUSION: In patients with colonic diverticulitis, CMZ therapy should be selected because of the adequate clinical outcomes and lower incidence of adverse events, as this would reduce broad-spectrum antibiotic use and minimize antibiotic-resistant bacteria.

Impact of antimicrobial stewardship implementation on the antibiotic use and susceptibility in a Japanese long-term care hospital.

BACKGROUND: Antimicrobial use (AMU) is closely related to the emergence of antimicrobial-resistant (AMR) bacteria. Meanwhile, long-term care hospitals (LTCHs) have been pointed out to be important reservoirs for AMR. However, evidence illustrating the association between AMU and AMR in LTCHs is lacking compared to that of acute care hospitals. METHODS: We evaluated the impact of an antimicrobial stewardship (AS) program implementation, in a LTCH on AMU and antibiotic susceptibility between three periods: the pre-AS-period (pre-AS); the first period after AS implementation (post-AS 1), in which initiated recommendation the blood culture collection and definitive therapy by AS team; and the second period (post-AS 2), implementation of a balanced use of antibiotics was added. RESULTS: After the AS implementation, a significant increase in the number of blood cultures collected was observed. Conversely, the AMU of piperacillin-tazobactam (PIPC/TAZ), which has activity against Pseudomonas aeruginosa, was increased and occupied 43.0% of all injectable AMU in post-AS 1 compared with that in pre-AS (35.5%). In the post-AS 2 period, we analyzed the %AUD and recommended hospital-wide PIPC/TAZ sparing; this resulted in the significant reduction in %AUD of PIPC/TAZ, which was associated with improved susceptibility of P. aeruginosa to PIPC/TAZ. CONCLUSIONS: These results suggest that AS programs aimed at implementing antibiotic sparing may lead to improve AMR, highlighting the necessity of correcting overuse of a single class of antibiotics and usefulness of AMU monitoring in the LTCH setting.

Comparative effectiveness of cefmetazole versus carbapenems and piperacillin/tazobactam as initial therapy for bacteremic acute cholangitis: A retrospective study.

INTRODUCTION: Carbapenems and piperacillin/tazobactam (PIPC/TAZ) are commonly used as the initial therapy to treat extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales in acute cholangitis. However, the overuse of these antibiotics contributes to the spread of antimicrobial resistance. Cefmetazole (CMZ) is stable to hydrolysis by ESBLs, so it may be an alternative to carbapenems and PIPC/TAZ. However, the effectiveness of CMZ compared with that of carbapenems and PIPC/TAZ as the initial therapy for acute cholangitis is unknown. METHODS: We conducted a retrospective cohort study at a university hospital between April 1, 2014, and December 31, 2022. Patients with bacteremic acute cholangitis who received CMZ, carbapenems, or PIPC/TAZ as the initial therapy were included. The patients were divided into a CMZ group and a carbapenems or PIPC/TAZ (CP) group to compare patient outcomes. RESULTS: A total of 99 patients (54 in the CMZ group and 45 in the CP group) were analyzed. The baseline characteristics of the patients were similar and 30-day mortality did not differ between groups (4% vs. 7%, P = 0.66). However, the CMZ group had a shorter length of stay (LOS) (8 days vs. 15 days, P < 0.001) and lower mean antibiotic cost (98.92 USD vs. 269.49 USD, P < 0.001) than the CP group. CONCLUSIONS: In bacteremic acute cholangitis, initial therapy with CMZ may contribute to a shorter LOS and lower antibiotic costs than treatment with carbapenems and PIPC/TAZ, without worsening patient outcomes.

Impact of a hospital sepsis management protocol on the selection of empirical antibiotics in infectious disease consultations.

It is well-established that Infectious Diseases consultation (IDC) enhances the prognosis of bloodstream infections. However, it is unclear if adoption of an institutional sepsis protocol would lead to any further improvement in a setting where IDC and infectious diseases approval (IDA) - available throughout 7 days/24 hours -are mandatory for administering broad spectrum antibiotics. We aimed to evaluate the influence of the institutional sepsis protocol developed by Department of Infectious Diseases and Clinical Microbiology on the selection of appropriate empirical antibiotics by IDC through focusing on patients who had bloodstream infections caused by Extended-spectrum ß-lactamase (ESBL) producing Escherichia coli and Klebsiella pneumoniae, which poses a therapeutic challenge. One hundred and fifty-three adult patients (58 patients in the pre-protocol period and 95 patients in the post-protocol period), who received empirical antibiotic treatment for ESBL-producing E. coli and K. pneumoniae, in whom at least one systemic antibiotic was started either on the day blood cultures were drawn or not later than 24 hours were included in the study, retrospectively. The primary outcome was whether the empirical treatment regimen included a carbapenem that was accepted as the appropriate treatment based on the results of the MERINO trial. Secondary outcomes included empirical treatment based on pre-defined risk factors suggesting multidrug resistance (MDR), 30-day inpatient mortality, and appropriate antibacterial treatment according to antimicrobial susceptibility test (AST) results. The median age (Interquartile range) was 61 (48-70.5) years and 76 (49.7%) out of 153 patients were male. The patients in the post-protocol period were older compared to the pre-protocol period (54 years vs 64 years, p = 0.045). The Charlson Comorbidity Index was higher during the post-protocol period compared to the pre-protocol period (4 vs 5, p=0.038). At least one risk factor for MDR bacteria infection was present in 147 (96.1%) of the 153 patients. While the rate of risk factors for MDR bacteria infections did not differ significantly between the pre-protocol and post-protocol periods, the post-protocol period showed a significantly higher level of appropriate antibiotic treatment according to the presence of MDR risk factors compared to the pre-protocol period (44.8% vs 64.2%, p=0.019). There was a significant increase in the use of carbapenems in the post-protocol period compared to the pre-protocol period (34.5% vs. 56.8%, p=0.007). When the subgroup of patients who were likely to have infection caused by ESBL-producing bacteria is taken into consideration, the carbapenem use was more frequent in the post-protocol period (37.8% vs 68.9%, p=0.002). The rate of appropriate empirical treatment according to AST was not statistically different between pre-protocol and post-protocol period. The 30-day mortality rates were similar in both periods (24.1% vs 31.5, p=0.33). However, the rate of susceptibility to piperacillin-tazobactam was statistically higher in the pre-protocol period (82.6% vs 46.2%, p=0.016) when 39.7% of the patients received piperacillin-tazobactam as the empirical treatment. This study highlights the significance of using a structured protocol to attain appropriate empirical treatment for patients suspected of sepsis, even in a setting where IDC is readily available.

The Dosage Recommendation of Cyclosporin in Children with Hemophagocytic Lymphohistiocytosis based on Population Pharmacokinetic Model.

OBJECTIVES: Cyclosporin is one of the therapeutic regimens for hemophagocytic lymphohistiocytosis (HLH); however, the optimal dosage of cyclosporine in children with HLH is unknown. It has been found that piperacillin-tazobactam affects the cyclosporine pharmacokinetic process in pediatric HLH patients. Thus, the purpose of the present study was to recommend cyclosporin dosage for pediatric HLH with and without piperacillin- tazobactam. METHODS: A previously established cyclosporine population pharmacokinetic model for pediatric HLH patients has been used in this study to recommend optimal dosage based on Monte Carlo simulation. The pediatric HLH patients have been included in eight weight groups (5, 10, 20, 30, 40, 50, 60, 70 kg) for sixteen dosages (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 mg/kg), split into one dose or two doses. RESULTS: The optimal cyclosporin dosages for children having HLH without piperacillin-tazobactam have been found to be 15, 13, 12, 11, 10, and 9 mg/kg, split into two doses for weights of 5-7, 7-10, 10-20, 20-28, 28-45, and 45-70 kg, respectively. For children with HLH, optimal cyclosporin dosages with piperacillin-tazobactam have been found to be 8 and 7 mg/kg, split into two doses for weights of 5-20 and 20-70 kg, respectively. CONCLUSION: It is the first time that the cyclosporin dosage regimens for HLH in children have been developed based on Monte Carlo simulation, and the initial dosage optimizations of cyclosporine in pediatric HLH patients have been recommended.

Accuracy of antibiotic concentrations in drug dispensing in neonates: a laboratory-based study.

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 (MA) was diluted once and the volumes of 5% glucose for MA were meropenem 4.00 mL, cefoperazone/sulbactam 3.00 mL, piperacillin/tazobactam 9.00 mL. Method B (MB) differed by doubling the volume of 5% glucose. The difference in method C (MC) 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 MA/MB/MC 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%. MB was better than MA in all three drugs. No difference in RE values was found between single and double dilution, except meropenem with 0.25 g. Using MB, meropenem and piperacillin/tazobactam with small drug strength had higher accuracy in preparation. CONCLUSIONS: MB 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.

Antibiotic resistance profiles and associated factors of Pseudomonas Infections among patients admitted to large tertiary care hospital from a developing country.

BACKGROUND: Pseudomonas infections are among the most common infections encountered in hospitalized patients, especially those with chronic illnesses or an immunocompromised state. Management of these infections has become challenging due to increased antibiotic resistance. Therefore, this study examines the antibiotic resistance profiles of Pseudomonas spp. and the associated factors among patients admitted to a large tertiary hospital in a developing country. METHODS: This retrospective observational chart review study assessed patients admitted to a large tertiary hospital in a developing country with a positive culture growth of Pseudomonas from anybody site. Antibiotic susceptibility of the isolated Pseudomonas and patient characteristics were studied from the start of 2021 to the end of 2022. The study ground consisted of 185 patients. RESULTS: The study included 185 patients with positive Pseudomonas isolates. Males constituted 54.6% of the sample, while 45.4% were females. The median age of the patients was 53 years. Patient comorbidities and risk factors for Pseudomonas infection and multidrug resistance were assessed. Antibiotic resistance to the Pseudomonas regimens showed the highest resistance to meropenem and ciprofloxacin (23.4%, similarly) among isolates of Pseudomonas aeruginosa. Multidrug resistance (MDR) was found in 108 (58.4%) isolates. The most commonly used antibiotic for treatment was piperacillin-tazobactam, accounting for 33.3% of cases, followed by aminoglycosides at 26.6%. CONCLUSIONS: Pseudomonas aeruginosa isolates were resistant to meropenem and ciprofloxacin. Over half of the isolates were multidrug-resistant, which was worrying. Piperacillin-tazobactam and aminoglycosides were the most often utilized antibiotics, highlighting the significance of susceptibility testing. Implementing antimicrobial stewardship programs and infection control measures can help reduce drug resistance and improve outcomes in Pseudomonas infections.

Epidemiology and impact of methicillin-sensitive Staphylococcus aureus with ß-lactam antibiotic inoculum effects in adults with cystic fibrosis.

Staphylococcus aureus is the most prevalent cystic fibrosis (CF) pathogen. Several phenotypes are associated with worsened CF clinical outcomes including methicillin-resistance and small-colony-variants. The inoculum effect (IE) is characterized by reduced ß-lactam susceptibility when assessed at high inoculum. The IE associates with worse outcomes in bacteremia and other high-density infections, and may therefore be relevant to CF. The prevalence of IE amongst a CF cohort (age ≥18 years), followed from 2013 to 2016, was investigated. Yearly methicillin-sensitive S. aureus (MSSA) isolates were screened at standard (5 × 105 CFU/mL) and high (5 × 107 CFU/mL) inoculum against narrow-spectrum anti-Staphylococcal ß-lactams and those with anti-pseudomonal activity common to CF. A ≥ 4-fold increase in minimum inhibitory concentration between standard and high inoculum defined IE. Isolates underwent blaZ sequencing and genotyping and were compared against published genomes. Fifty-six percent (99/177) of individuals had MSSA infection. MSSA was observed at ≥105 CFU/mL in 44.8% of entry sputum samples. The prevalence of the IE was 25.0%-cefazolin; 13.5%-cloxacillin; 0%-meropenem; 1.0%-cefepime; 5.2%-ceftazidime; and 34.4%-piperacillin-tazobactam amongst baseline MSSA isolates assessed. blaZ A associated with cefazolin IE (P = 0.0011), whereas blaZ C associated with piperacillin-tazobactam IE (P < 0.0001). Baseline demographics did not reveal specific risk factors for IE-associated infections, nor were long-term outcomes different. Herein, we observed the IE in CF-derived MSSA disproportionally for cefazolin and piperacillin-tazobactam and this phenotype strongly associated with underlying blaZ genotype. The confirmation of CF being a high density infection, and the identification of high prevalence of MSSA with IE in CF supports the need for prospective pulmonary exacerbation treatment studies to understand the impact of this phenotype.