At least half of the achievement gap for low-income, minority children is present at kindergarten entry; however, there are no population-level early childhood interventions that effectively engage and support families and teachers to ameliorate the impact of adversity on achievement.

This study evaluated ParentCorps, a family-centered, school-based intervention to promote self-regulation and learning for all children entering school in disadvantaged, urban neighborhoods. ParentCorps results in higher kindergarten achievement among low-income, minority children. (Read the full article)

The United States switched from whole-cell to acellular pertussis vaccines during the 1990s. Whether pertussis risk during a California outbreak differed between teenagers who previously received whole-cell or acellular pertussis vaccines early in life has not been reported.

We evaluated pertussis risk in 10 to 17 year olds at Kaiser Permanente Northern California during a recent pertussis outbreak. Those given whole-cell pertussis vaccines in childhood were more protected than those given acellular pertussis vaccines. (Read the full article)

Feeding difficulties often emerge during the neonatal period and affect neonatal growth. Growth throughout the first years of life is associated with children’s IQ scores and risk of behavioral problems.

Among infants born full term (≥37 weeks’ gestation) with birth weight ≥2500 g, gain in weight and head circumference during the neonatal period is associated with higher IQ, but not with behavior at 6.5 years of age. (Read the full article)

Child maltreatment is a serious and prevalent public health problem in the United States. Responsible for substantial morbidity and mortality, maltreatment affects children's physical and mental health.

Although many health impacts of child maltreatment have been documented, no claims-based study has quantified the impact of maltreatment on health service utilization and costs. This study presents systematic claims-based estimates of maltreatment impacts on utilization and costs for the Medicaid population. (Read the full article)

Although studies have examined family socioeconomic status as income and educational and employment status, emerging research suggests indicators of material hardship, such as diaper need, are increasingly important to child health. Diaper need has not been examined in the scientific literature.

This study quantifies diaper need, proposes a method to measure diaper need, and explores psychosocial and demographic variables associated with diaper need in a large sample of low-income families. (Read the full article)

Previous research on potential deleterious effects of typically developing children growing up in households with children with disability has produced mixed results. Research methods have been cited as a problem in many studies.

This is the largest known empirical study comparing functional impairment in siblings living with a child with disability and siblings residing with children who are typically developing. This study also follows the trajectory of functional impairment across 2 measurement periods. (Read the full article)

Tympanometry provides a measure of middle ear function. There has been no description of the relationship between measurements of middle ear function in the absence of gross anatomic defects and clinical outcome among children with acute nontraumatic coma.

This study reveals an unexpected association between abnormal middle ear function and death in childhood acute coma. These findings call for more investigations on the relationship between middle and inner ear anatomy and function and intracranial dynamics and clinical outcomes. (Read the full article)

The 1-dose childhood varicella vaccination program in the United States resulted in dramatic declines in varicella incidence, hospitalizations, and deaths. There is little information on the impact of the 2006 recommendation for 2-dose varicella vaccination of children on varicella epidemiology.

In the first 5 years of the 2-dose varicella vaccination program, declines in varicella incidence were seen in all age groups, including infants who are not eligible for varicella vaccination, providing evidence of the benefit of high population immunity. (Read the full article)

Several studies have been published evaluating the impact of 2011 Accreditation Council for Graduate Medical Education duty hour regulations. Although resident quality of life may be improved, it appears that resident education and patient care may be worse.

This is the first study to evaluate pediatric program director approval of 2011 Accreditation Council for Graduate Medical Education Common Program Requirements and the perceived impact of the regulations on patient care, resident education, and quality of life. (Read the full article)

Broad-spectrum antibiotics are frequently used to empirically treat children hospitalized with community-acquired pneumonia despite recent national recommendations to use narrow-spectrum antibiotics.

Narrow-spectrum antibiotics are similar to broad-spectrum antibiotics for the treatment of children hospitalized with community-acquired pneumonia in terms of clinical outcomes and resource utilization. This study provides scientific evidence to support national consensus guidelines. (Read the full article)

Payment arrangements that blend global budgets with pay-for-performance are proliferating. However, little is known about how these contracts affect pediatric health care quality and spending for children with and without special health care needs receiving care from large provider organizations.

A prototypical global budget contract significantly improved preventive care quality measures tied to pay-for-performance, especially for children with special health care needs. It did not alter trends for spending or for quality measures that were not tied to pay-for-performance. (Read the full article)

Congenital cytomegalovirus (CMV) infection is a leading cause of sensorineural hearing loss and neurodevelopmental impairment in full-term infants. The incidence of congenital CMV infection in preterm infants and the possible associations with developmental outcomes are unknown.

This study defines the incidence of congenital CMV infection in very low birth weight infants and identifies strong associations of congenital CMV infection with hearing loss and adverse neurodevelopmental outcomes in this population. (Read the full article)

Motor vehicle crashes, heavy drinking, and drug use are serious, interactive health concerns for the teenage population. Teenage alcohol-impaired driving behaviors are associated with heavy drinking, parenting practices, and exposure to drinking and driving.

Earliness of exposure to alcohol/drug impaired driving (DWI) and early licensure were independent risk factors for teenage DWI. A strong, positive dose-response existed between DWI and amount of prior exposure to DWI in the form of riding with an impaired driver. (Read the full article)

Physical activity interventions aimed at improving body composition in childhood have had limited success and often targeted overweight children. Therefore, the efficacy of physical activity randomized controlled trials in improving body composition among children with varying adiposity levels remains unknown.

This randomized controlled trial demonstrated that a physical activity program designed to meet daily physical activity recommendations can improve cardiorespiratory fitness, decrease total fat mass, and prevent accumulation of central adiposity in a group of children with varying adiposity levels. (Read the full article)

Approximately 20% of US child passenger deaths involve an alcohol-impaired driver, typically in the child’s own vehicle. The higher the blood alcohol concentration of a driver, the more likely his or her child passenger was unrestrained in the fatal crash.

The risk of a child passenger dying while being transported with an alcohol-impaired driver varies meaningfully across states. These state-specific rates may help to inform renewed prevention efforts. (Read the full article)

Rapid cranial MRI is a radiation-free method to assess children with possible ventricular shunt malfunction. However, the test performance of rapid cranial MRI has never been compared with that of cranial CT, the current reference standard.

The accuracy of rapid cranial MRI was not inferior to that of CT for diagnosing ventricular shunt malfunction. Rapid cranial MRI is an important radiation-sparing diagnostic alternative for children presenting emergently with possible ventricular shunt malfunction. (Read the full article)

Varicella vaccine is effective, but there is concern that widespread use in young children may lead to a shift in the age of infection, with potentially more severe disease later in childhood and adolescence.

This study documents that varicella vaccine resulted in a decline of varicella incidence and hospitalization in all age groups, with no shift to older age groups. (Read the full article)

Most therapeutic products used in children have not been studied in that population. There is a need for special incentives and market protection (pediatric exclusivity) to compensate drug sponsors for studying these products in children.

Of 189 products studied under pediatric exclusivity, 173 (92%) received new labeling information. Pediatric efficacy was not established for 78 (42%), including 81% of oncology drugs. Probability of demonstrating efficacy was related to therapeutic area and year exclusivity was granted. (Read the full article)

Recent concussion research has examined the role of impact location (ie, the area on the head to which impact occurred); however, no studies exist regarding impact location’s association with concussion outcomes (eg, symptomatology, symptom resolution time, return to play).

This study is the first to examine the association of impact location and concussion outcomes in young athletes. Our findings suggest that impact location, as assessed by sideline observers/player report, is likely of little use in predicting clinical outcomes. (Read the full article)

It is thought that vaccination coverage increases during and immediately after an infectious disease epidemic; however, little evidence exists to support this phenomenon.

The 2011 to 2012 pertussis epidemic did not significantly change the proportion of infants in Washington State who were up to date for pertussis-containing vaccines. This finding may challenge conventional wisdom that vaccine acceptance uniformly increases when risk of disease is high. (Read the full article)

Quality improvement (QI) studies generally do not account for concurrent trends of improvement and it is difficult to distinguish the impact of a multihospital collaborative QI project without a contemporary control group.

A multihospital collaborative QI model led to greater declines in hypothermia and invasive ventilation rates in the delivery room compared with an individual NICU QI model and NICUs that did not participate in formal QI activities. (Read the full article)

IP-10 is a novel immunologic marker for tuberculosis (TB) infection. It has been suggested that IP-10 may perform better in children compared with the QuantiFERON test, but only a few studies have investigated IP-10 for diagnosing active TB in children.

This study is the first to investigate IP-10 and QuantiFERON for diagnosing TB in children by using consensus classifications. Both IP-10 and QuantiFERON exhibited poor performance in children from a high-burden setting, and performance was especially compromised in young children. (Read the full article)

Migraine headaches are a common presenting complaint in emergency departments. Abortive treatment in this setting is not well studied, leading to considerable variation in treatment. The relationship between acute medications and emergency department revisits has not been studied.

Eighty-five percent of children with migraine are successfully discharged from the emergency department; only 1 in 18 children require a return visit. Prochlorperazine is associated with less revisits than metoclopramide, and diphenhydramine use is associated with increased risk of return visits. (Read the full article)

Medical home transformation is led by practice-level assessment, but much of the evidence supporting the medical home derives from individual-level assessment based on parental perception. The association between these 2 levels of assessment is unknown.

Among Boston-area community health centers, there was no association between the individual- and practice-level assessments of the medical home. This highlights the need for studies supporting the child health benefits of medical home practice transformation. (Read the full article)

Early-life lower respiratory illnesses, including pneumonia, are associated with increased prevalence of asthma and diminished lung function in children. Whether early-life pneumonia is associated with subsequent impaired lung function and asthma in adults is not yet clear.

This is the first article providing strong data for an association between early-life pneumonia in an outpatient setting and airflow limitation and asthma into adulthood, supporting the hypothesis of the early-life origins of chronic obstructive pulmonary disease. (Read the full article)

Collaborative care is known to be an effective system to manage child behavioral health conditions in the primary care setting.

Among urban children with attention-deficit/hyperactivity disorder, using lay care managers to address barriers to engagement with care and challenging child behaviors has the potential to improve the effectiveness of conventional collaborative care. (Read the full article)

Trainee success rates with infant lumbar puncture are poor. The model of just-in-time learning via simulation has produced clinical improvement for other medical skills such as cardiac compressions and central line dressing changes.

This is the first study to evaluate the impact of just-in-time-and-place simulation-based learning on success with infant lumbar puncture. The intervention improved clinical behaviors associated with success without making a significant impact on success with the procedure. (Read the full article)

Otorrhea is common in children with tympanostomy tubes: annually, 2 of 3 children develop 1 or more episodes. Antibiotic-glucocorticoid eardrops are the most effective treatment in both the short- and long-term.

Treatment with antibiotic-glucocorticoid eardrops costs less than oral antibiotics and initial observation in children with tympanostomy tubes who develop otorrhea. Non–health care costs constitute a substantial proportion of the total costs of this condition. (Read the full article)

Dyslexia has a lifelong impact on learning. The consensus in the literature from clinical studies is that dyslexia is not caused by vision abnormalities. However, interventions and therapies directed at eye-related functions are still available.

In this cohort the majority of dyslexic children had normal results for all ophthalmic tests. These population-based data support the consensus that dyslexia is not primarily a vision problem and that vision-based therapies are not justified or likely to help. (Read the full article)

Pediatric patients suffer higher mortality due to the shortage of transplantable organs. Factors influencing families’ donation decisions are similar for pediatric and adult patients. However, the general perception that families of pediatric patients are less willing to donate persists.

Communication emerged as a critical factor of family authorization, reinforcing its importance in the organ donation process. Patient age (ie, adult versus pediatric) was not predictive of family authorization. (Read the full article)

Gastrostomy tube placement is a difficult decision for families of children with neurologic impairment. Better understanding the impact of these tubes on the lives of children and families will help improve decision-making and support from health care providers.

Gastrostomy tube placement has broad-reaching implications for children and their families. There are physical, emotional, and relational challenges and benefits for the child, the parents, and the family unit. Exploring potential outcomes with families may improve decision-making conversations and support. (Read the full article)

Selective eating is a common, burdensome eating pattern in young children. A significant subset remain selective eaters at least until adolescence and, for some, adulthood. The question is whether selective eating is a serious enough developmental pattern to warrant intervention.

This study examines whether selective eating, at 2 levels of severity, is associated with current and future psychological problems. Because moderate levels of selective eating were associated with impairment, selective eating falls within the diagnosis of avoidant/restrictive food intake disorder. (Read the full article)

Rudeness is routinely experienced by hospital-based medical teams. Individuals exposed to mildly rude behavior perform poorly on cognitive tasks, exhibit reduced creativity and flexibility, and are less helpful and prosocial.

Rudeness had adverse consequences on diagnostic and procedural performance of members of the NICU medical teams. Information-sharing mediated the adverse effect of rudeness on diagnostic performance, and help-seeking mediated the effect of rudeness on procedural performance. (Read the full article)

Minister of Finance Tito Mboweni has announced a number of "exceptional tax measures as part of the fiscal package outlined by President Cyril Ramaphosa to fight the coronavirus pandemic.

This year at the sports and English camp in Bulgaria, the team noticed the fruit of building on relationships over time.

The unexpected transition to online classes due to the COVID-19 pandemic has prompted many changes for undergraduate students and their instructors. To understand the magnitude of these impacts and potentially improve digital learning, researchers in the Penn State School of Engineering Design and Professional Programs have received a $196,136 grant from the National Science Foundation.

The Newseum in Washington has just launched Decision 2012: Exploring Elections and the Media, an online resource for teaching about the presidential campaign and election.

A recent study found that one organization's instructional-leadership professional development had no impact. Could it be because the topic of instructional leadership needs to be expanded?

Sony reinvented the premium point-and-shoot camera in 2012 with the RX100. It's continued to build out the series, but has also kept older models on sale. We're here to help you find the right one to suit your needs.

The McGregor BFA table showed surprising ‘all-rounder’ listings in the top 30 rankings.

While the prospect of Guinea's return to constitutional rule after its recent election is cause for hope, the recent resurgence of military takeovers in Africa may not yet have run its full course.

For more than a year and a half, UN peacekeepers have continuously supported military operations conducted by the Congolese armed forces (FARDC) against the Rwandan rebels of the Democratic Forces for the Liberation of Rwanda (FDLR) in North and South Kivu.

Burundi risks reversing the decade of progress it has enjoyed since its civil war ended unless the government resumes political dialogue with the opposition.

Since 2012, single low dose of primaquine (SLDPQ, 0.25mg/kg) has been recommended with artemisinin-based combination therapies, as first-line treatment of acute uncomplicated Plasmodium falciparum malaria, to interrupt its transmission, especially in low transmission settings of multidrug, including artemisinin, resistance. Policy makers in Cambodia have been reluctant to implement this recommendation due to primaquine safety concerns and lack of data on its efficacy.

In this randomized controlled trial, 109 Cambodians with acute uncomplicated P. falciparum malaria received dihydroartemisinin-piperaquine (DP) alone or combined with SLDPQ on the first treatment day. Transmission-blocking efficacy of SLDPQ was evaluated on Days 0, 1, 2, 3, 7, 14, 21, 28 and recrudescence by reverse transcriptase polymerase chain reaction (RT-PCR) (gametocyte prevalence) and membrane-feeding assays with Anopheles minimus mosquitoes (gametocyte infectivity). Without the influence of recrudescent infections, DP+SLDPQ reduced gametocyte carriage 3 fold compared to DP. Of 48 patients tested on Day 0, only three patients were infectious to mosquitoes (~6%). Post-treatment, three patients were infectious: on D14 (3.5%, 1/29), and on the first and seventh day of recrudescence (8.3%, 1/12 for each); this overall low infectivity precluded our ability to assess its transmission blocking efficacy.

Our study confirms effective gametocyte clearance of SLDPQ when combined with DP in multidrug resistant P. falciparum and the negative impact of recrudescent infections due to poor DP efficacy. Artesunate-mefloquine (ASMQ) has replaced DP and ASMQ-SLDPQ has been deployed to treat all P. falciparum symptomatic patients to further support the elimination of multidrug resistant P. falciparum in Cambodia.

Carbapenems are currently the preferred agents for the treatment of serious Acinetobacter infections. However, whether cefepime/cefpirome can be used to treat Acinetobacter bloodstream infection (BSI) if it is active against the causative pathogens is not clear. This study aimed to compare the efficacy of cefepime/cefpirome and carbapenem monotherapy in patients with Acinetobacter BSI. The population included 360 patients with monomicrobial Acinetobacter BSI receiving appropriate antimicrobial therapy admitted to four medical centres in Taiwan in 2012–2017. The predictors of 30-day mortality were determined by Cox regression analysis. The overall 30-day mortality rate in the appropriate antibiotic treatment group was 25.0% (90/360 patients), respectively. The crude 30-day mortality rates for cefepime/cefpirome and carbapenem therapy were 11.5% (7/61 patients) and 26.3% (21/80 patients), respectively. The patients receiving cefepime/cefpirome/carbapenem therapy were infected by Acinetobacter nosocomialis (51.8%), A. baumannii (18.4%) and A. pittii (12.1%). After adjusting for age, Sequential Organ Failure Assessment (SOFA) score, invasive procedures, and underlying diseases, cefepime/cefpirome therapy was not independently associated with a higher or lower 30-day mortality compared to the carbapenem therapy. SOFA score (hazard ratio [HR], 1.324; 95% confidence interval [CI], 1.137–1.543; P < 0.001) and neutropenia (HR, 7.060; 95% CI, 1.607–31.019; P = 0.010) were independent risk factors for 30-day mortality of patients receiving cefepime/cefpirome or carbapenem monotherapy. The incidence density of 30-day mortality for cefepime/cefpirome versus carbapenem therapy was 0.40% versus 1.04%. The therapeutic response of cefepime/cefpirome therapy was comparable to that of carbapenems among patients with Acinetobacter BSI receiving appropriate antimicrobial therapy.

Background: Intensive care unit (ICU) patients may experience ceftriaxone underexposure but clinical outcomes data are lacking. The objective of this study was to determine the impact of ceftriaxone dosing on clinical outcomes amongst ICU patients without central nervous system (CNS) infection.

Methods: A retrospective study of ICU patients receiving intravenous, empiric ceftriaxone for non-CNS infections was conducted. Patients ≥18 years of age who received ≤2 grams of ceftriaxone daily for ≥72 hours were included and categorized as receiving ceftriaxone 1 gram or 2 grams daily. The primary, composite outcome was treatment failure: inpatient mortality and/or antibiotic escalation due to clinical worsening. Propensity score matching was performed based on the probability of receiving ceftriaxone 2 grams daily. Multivariable logistic regression determined the association between ceftriaxone dose and treatment failure in a propensity-matched cohort.

Results: A total of 212 patients were included in the propensity-matched cohort. The most common diagnoses (83.0%) were pneumonia and urinary tract infection. Treatment failure occurred in 17.0% and 5.7% of patients receiving 1 gram and 2 grams daily, respectively (p=0.0156). Overall inpatient mortality was 8.5%. Ceftriaxone 2 gram dosing was associated with a reduced likelihood of treatment failure (adjusted odds ratio=0.190; 95% confidence interval: 0.059 – 0.607). Other independent predictors of treatment failure included sequential organ failure assessment score (aOR 1.440, 95% CI 1.254 – 1.653) and creatinine clearance at 72 hours from ceftriaxone initiation (aOR 0.980, 95% CI (0.971 – 0.999).

Conclusions: Ceftriaxone 2 grams daily when used as appropriate antimicrobial coverage may be appropriate for ICU patients with lower mortality risk.

Objectives: Carbapenemase-producing Enterobacterales and specifically KPC-producing Klebsiella pneumoniae (KPC-Kp) are rapidly spreading worldwide. The prognosis of ventilator-associated pneumonia (VAP) caused by KPC-producing Klebsiella pneumoniae (KPC-Kp) is not well known. Our study tries to assess whether ventilator-associated pneumonia caused by a KPC-Kp strain is associated with higher all-cause mortality than if caused by carbapenem-susceptible isolates.

Study design and methods: This is a retrospective cohort study of patients with VAP due to K. pneumoniae from a 35-bed polyvalent Intensive Care Unit in a university hospital (> 40,000 annual admissions) between January 2012 and December 2016. Adjusted multivariate analysis was used to study the association of KPC-Kp with 30-day all-cause mortality (Cox regression).

Results. We analyze 69 cases of K. pneumoniae VAP of which 39 were produced by a KPC-Kp strain with high-level resistance to meropenem (MIC > 16 mg/mL). All-cause mortality at 30 days was 41% in the KPC-Kp group (16/39) and 33.3% in the carbapenem-susceptible cases (10/30). KPC-Kp etiology was not associated with higher mortality when controlled for confounders (adjusted hazard ratio [lsqb]HR[rsqb] 1.25; 95% CI: 0.46–3.41). Adequate targeted therapy (HR 0.03; 95% CI: <0.01–0.23) was associated with all-cause mortality.

Conclussion. Assuming the limitations due to the available sample size, the prognosis of VAP caused by KPC-Kp is similar to VAPs caused by carbapenem-susceptible K. pneumoniae when appropriate treatment is used.

QPX7728 is an ultra-broad-spectrum boronic acid beta-lactamase inhibitor that demonstrates inhibition of key serine and metallo beta-lactamases at a nano molar range in biochemical assays with purified enzymes. The broad-spectrum inhibitory activity of QPX7728 observed in biochemical experiments translates into enhancement of the potency of many beta-lactams against strains of target pathogens producing beta-lactamases. The impact of bacterial efflux and permeability on inhibitory potency were determined using isogenic panels of KPC-3 producing isogenic strains of K. pneumoniae and P. aeruginosa and OXA-23-producing strains of A. baumannii with various combinations of efflux and porin mutations. QPX7728 was minimally affected by multi-drug resistance efflux pumps in either Enterobacteriaceae, or in non-fermenters such as P. aeruginosa or A. baumannii. In P. aeruginosa, the potency of QPX7728 was further enhanced when the outer membrane is permeabilized. The potency of QPX7728 in P. aeruginosa is not affected by inactivation of the carbapenem porin OprD. While changes in OmpK36 (but not OmpK35) reduced the potency of QPX7728 (8-16-fold), QPX7728 (4 μg/ml) nevertheless completely reversed KPC-mediated meropenem resistance in strains with porin mutations, consistent with a lesser effect of these mutations on the potency of QPX7728 compared to other agents. The ultra-broad-spectrum beta-lactamase inhibition profile combined with enhancement of the activity of multiple beta-lactam antibiotics with varying sensitivity to the intrinsic resistance mechanisms of efflux and permeability indicate QPX7728 is a useful inhibitor for use with multiple beta-lactam antibiotics.

Omadacycline is a novel aminomethylcycline with activity against Gram-positive and -negative organisms, including Haemophilus influenzae, which is one of the leading causes of community-acquired bacterial pneumonia (CABP). The evaluation of antimicrobial agents against H. influenzae using standard murine infection models is challenging due to the low pathogenicity of this species in mice. Therefore, 24-hour dose-ranging studies using a one-compartment in vitro infection model were undertaken with the goal of characterizing the magnitude of the ratio of the area under the concentration-time curve (AUC) to the MIC (AUC/MIC ratio) associated with efficacy for a panel of five clinical H. influenzae isolates. These five isolates, which had MIC values of 1 or 2 mg/L, were exposed to omadacycline total-drug epithelial lining fluid (ELF) concentration-time profiles based on those observed in healthy volunteers following intravenous omadacycline administration. Relationships between change in log₁₀ colony forming units (CFU) from baseline at 24 hours and total-drug ELF AUC/MIC ratio for each isolate and the isolates pooled together were evaluated using Hill-type models and non-linear least squares regression. As evidenced by the high coefficient of determination (r²) of 0.88 to 0.98, total-drug ELF AUC/MIC ratio described the data well for each isolate and the isolates pooled together. The median total-drug ELF AUC/MIC ratio associated with net bacterial stasis and 1- and 2-log₁₀ CFU/mL reductions from baseline at 24 hours was 6.91, 8.91, and 11.1, respectively. These data were useful to support the omadacycline dosing regimens selected for the treatment of patients with CABP, as well as susceptibility breakpoints for H. influenzae.

Pharmacokinetic changes are often seen in patients with severe infections. Administration by continuous infusion has been suggested to optimize antibiotic exposure and pharmacokinetic/pharmacodynamic (PK/PD) target attainment for β-lactams. In an observational study, unbound piperacillin concentrations (n=196) were assessed in 78 critically ill patients following continuous infusion of piperacillin/tazobactam (ratio 8:1). The initial dose of 8, 12 or 16 g (piperacillin component) was determined by individual creatinine clearance (CRCL). Piperacillin concentrations were compared to the EUCAST clinical breakpoint MIC for Pseudomonas aeruginosa (16 mg/L), and the following PK/PD targets were evaluated: 100% fT>1xMIC and 100% fT>4xMIC. A population pharmacokinetic model was developed using NONMEM 7.4.3 consisting of a one-compartment disposition model with linear elimination separated into non-renal and renal (linearly increasing with patient CRCL) clearances. Target attainment was predicted and visualized for all individuals based on the utilized CRCL dosing algorithm. The target of 100% fT>1xMIC was achieved for all patients based on the administered dose, but few patients achieved the target of 100% fT>4xMIC. Probability of target attainment for a simulated cohort of patients showed, that increasing the daily dose by 4 g increments (piperacillin component) did not result in substantially improved target attainment for the 100% fT>4xMIC target. To conclude, in patients with high CRCL combined with high-MIC bacterial infections, even a CI regimen with a daily dose of 24 g may be insufficient to achieve therapeutic concentrations.