Recorded music, parent voices, and sung lullabies have been shown to increase oxygen saturation, nonnutritive sucking, and weight gain in premature infants.

Parent-preferred melodies and entrained live rhythm and breath sounds can enhance quiet alert and sleep states, suck response, and oxygen saturation in premature infants and significantly reduce fear and anxiety perception in parents. (Read the full article)

Perforation in the setting of retained esophageal foreign body is rare, but can be catastrophic. The role of imaging in screening for injury after removal has not previously been studied.

The rate of esophageal injury among children with retained esophageal foreign body is 1.3%. Intraoperative findings suggestive of injury are predictive of perforation. Routine chest radiography is not warranted in those who do not meet this criterion. (Read the full article)

Extremely preterm infants who receive antihypotensive therapy have worse outcomes than untreated infants. The reasons for this are not clear. High-quality randomized trials have not been performed to date because of logistical challenges, thereby necessitating alternative methods of investigation.

Antihypotensive therapy administration was not associated with improved in-hospital outcomes for any of the 15 definitions of low blood pressure investigated. Alternative methods of deciding who to treat are needed to maximize patient benefit and minimize harm. (Read the full article)

Cognitive behavioral therapy is an effective and safe treatment of chronic fatigue syndrome in children and adolescents. After 6 months, Internet-based cognitive behavioral therapy in the form of FITNET led to an 8 times higher chance of recovery compared with usual care.

The positive effects of FITNET were maintained at long-term follow-up (>2.5 years).Patients following usual-care treatment achieve similar recovery rates at long-term follow-up. (Read the full article)

Cognitive and behavioral problems after pediatric traumatic brain injury lead to poor functioning across multiple settings and can persist long-term after injury. Executive dysfunction is particularly common; however, there is a paucity of evidence-based interventions to guide treatment.

This study is among the largest randomized controlled trials performed in pediatric traumatic brain injury. It demonstrates the ability to use an online problem-solving-based intervention to improve caregiver ratings of executive dysfunction within 12 months after injury. (Read the full article)

Studies have highlighted a lack of patient awareness of potential increased cancer risks associated with computed tomography (CT) scans in adult patients and in nonurgent settings. However, little is known about parental awareness of these risks in an emergency setting.

Approximately half of parents were aware of the potential cancer risks from CT scans in an emergency setting. Although risk disclosure moderately reduced willingness to proceed with recommended testing, almost all parents preferred an informed discussion before CT imaging. (Read the full article)

Variation in the emergency department (ED) use of radiographs for asthma, bronchiolitis, and croup exists. Unnecessary radiographs contribute to higher costs of care, decreased ED efficiency, and increased radiation in children.

Despite no changes in guidelines to support routine use, there is a significant upward trend in the use of radiographs for children with emergency department visits for asthma. Pediatric-focused EDs use significantly fewer radiographs for asthma, bronchiolitis, and croup. (Read the full article)

Etiology and timing of onset of neonatal hypoxic-ischemic encephalopathy continue to be controversial. Previous studies suggest antepartum events are the main contributing factors, but have used a broad definition of encephalopathy and included infants with genetic, congenital, and developmental abnormalities.

Our study suggests that when strict criteria defining hypoxic-ischemic encephalopathy are applied with supporting neuroimaging evidence of an acute hypoxic-ischemic insult, intrapartum events are the final and necessary pathway leading to this condition. (Read the full article)

Pediatric functional abdominal pain is common and costly. Cognitive behavior therapy (CBT) is a promising treatment for these complaints, but solid evidence for its effectiveness is lacking.

This randomized controlled trial shows that CBT reduces abdominal pain in 60% of children 1 year after treatment. Six sessions of CBT delivered by trained master’s students in psychology were equally effective as 6 visits to an experienced pediatrician. (Read the full article)

Recent guidelines for the management of childhood pneumonia recommend narrow-spectrum antimicrobial agents (eg, ampicillin) for most children; however, few studies have directly compared the effectiveness of narrow-spectrum agents to the broader spectrum third-generation cephalosporins commonly used among children hospitalized with pneumonia.

By using data from 43 children’s hospitals in the United States, we demonstrate equivalent outcomes and costs for children hospitalized with pneumonia and treated empirically with either narrow- (ampicillin/penicillin) or broad-spectrum (ceftriaxone/cefotaxime) antimicrobial therapy. (Read the full article)

Previous studies have confirmed feasibility of MRI for diagnosis of appendicitis in adults and children. No study has assessed clinical end points when using ultrasound and MRI compared with computed tomography for diagnosis of appendicitis in children.

Radiation-free imaging with ultrasound selectively followed by MRI does not change clinical endpoints compared with CT for diagnosing appendicitis in children, with no difference in time to antibiotic administration, time to appendectomy, negative appendectomy rate, perforation rate, or length of stay. (Read the full article)

Little is known about the epidemiology and pathogenicity of Clostridium difficile infection among children, particularly those aged ≤3 years in whom colonization is common and pathogenicity uncertain.

Young children, 1 to 3 years of age, had the highest Clostridium difficile infection incidence. Considering that clinical presentation, outcomes, and disease severity were similar across age groups, C difficile infection in the youngest age group likely represents true disease and not asymptomatic colonization. (Read the full article)

Left heart defects, such as bicuspid aortic valve, are heritable. Echocardiography screening has been recommended for first-degree relatives of patients with left heart defects. Such screening may allow timely recognition of complications such as progressive aortic dilation.

This study examines the utility and cost of echocardiography screening of siblings of patients with bicuspid aortic valve in clinical practice. Screening has high yield, and the cost compares favorably with those of other screening methods used in pediatrics. (Read the full article)

Existing data do not demonstrate a need for combination therapy after antimicrobial susceptibility data indicate adequate in vitro activity with β-lactam monotherapy. However, the role of empirical combination therapy for the treatment of Gram-negative bacteremia in children remains unsettled.

We conducted a retrospective, propensity-score matched study demonstrating no improvement in 10-day mortality of children who have Gram-negative bacteremia receiving empirical β-lactam and aminoglycoside combination therapy compared with β-lactam monotherapy, unless the bacteremic episode was attributable to a multidrug-resistant organism. (Read the full article)

In parts of sub-Saharan Africa, sexual assault incidence among adolescents is as high as 24%, resulting in serious physical and mental health problems. In the United States, empowerment and self-defense training have been shown to decrease incidence of sexual assault.

This study evaluated an empowerment and self-defense training intervention for adolescent girls in the African context. This intervention proved highly effective at preventing sexual assault and should be replicable in other countries in sub-Saharan Africa and around the world. (Read the full article)

Home oxygen has been safely incorporated into emergency department management of bronchiolitis in certain populations. After discharge, a small proportion of patients (2.7%–6%) require subsequent admission. For patients managed successfully as outpatients, pediatricians report variable practice styles and comfort levels.

Our results define the clinical course and outpatient burden associated with discharge on home oxygen. By using an integrated health care system, we captured slightly higher rates (9.4%) of subsequent admission and found fever to be associated with this outcome. (Read the full article)

Hypothermia treatment of neonatal encephalopathy reduces death and disability from 66% to 50%; additional neuroprotective therapies are needed. We previously found in animal models that adding 50% xenon to the breathing gas during cooling doubled neuroprotection.

This clinical feasibility study used 50% xenon for 3 to 18 hours in 14 cooled infants with cardiovascular, respiratory, and amplitude-integrated EEG monitoring. This depressed seizures, with no blood pressure reduction. Xenon is ready for randomized clinical trials in newborns. (Read the full article)

Chorioamnionitis (CAM) is a major risk factor for early-onset neonatal sepsis. The Committee on the Fetus and Newborn recommends extending the duration of antimicrobial therapy in neonates exposed to CAM and intrapartum antibiotics if laboratory data are abnormal, even if culture results are sterile.

When managed by using a strategy similar to recent Committee on the Fetus and Newborn guidelines, a large number of term and late-preterm infants exposed to CAM who had sterile blood culture findings were treated with prolonged antibiotic therapy, subjected to additional invasive procedures, and had prolonged hospitalization. (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)

Animal studies document dose-dependent and duration-of-therapy-dependent fluoroquinolone cartilage toxicity in weight-bearing joints. Preliminary pediatric data collected after fluoroquinolone treatment and up to 1 year posttreatment in blinded and unblinded studies suggest the possibility of cartilage toxicity in children.

These are the first prospectively collected data on fluoroquinolone musculoskeletal safety collected posttherapy from randomized, comparative studies of respiratory tract infections and analyzed at 5 years. Long-term musculoskeletal adverse events occurred with equal frequency in both levofloxacin and comparator groups. (Read the full article)

Prescribing patterns in the US pediatric population are changing but not uniformly. A detailed examination of prescription variation is needed to better understand pharmacotherapy of children and to inform future exploration of the causes and consequences of diverse practices.

We examine pediatric pharmacotherapy and quantify payer type differences and small geographic area variation. Substantial payer-type differences and regional variations were found, likely reflecting local practice cultures. Variation was greatest for medications used in situations of diagnostic and therapeutic uncertainty. (Read the full article)

In HIV-infected children, decisions to start antiretroviral therapy must weigh immunologic benefits against potential risks. Current guidelines recommend using CD4 percentage and age when deciding to start treatment. Population-level effects of these factors on immunologic recovery are unknown.

Starting antiretroviral therapy at higher CD4 percentages and younger ages maximizes potential for immunologic recovery. However, not all benefits are sustained, and viral failure may occur. Our results help clinicians better weigh immunologic benefits against viral failure risks. (Read the full article)

Despite breastfeeding recommendations by the World Health Organization and the American Academy of Pediatrics, there is less agreement on appropriate use of infant solid foods. There are currently no well-established dietary guidelines for US infants that are similar to the Dietary Guidelines for Americans (aged >2 years).

Distinct dietary patterns exist among US infants and have differential influences on growth. Use of "Infant guideline solids" (vegetables, fruits, baby cereal, and meat) with prolonged breastfeeding is a promising healthy dietary pattern for infants after age 6 months. (Read the full article)

Phototherapy decreases bilirubin concentration in skin more rapidly than in blood. During and after phototherapy, transcutaneous bilirubin measurements are considered unreliable and therefore discouraged.

Transcutaneous bilirubin underestimates total serum bilirubin by 2.4 mg/dL (SD, 2.1 mg/dL) during the first 8 hours after phototherapy. This gives a safety margin of ~7 mg/dL below the treatment threshold to omit confirmatory blood sampling. (Read the full article)

Infants with Prader-Willi syndrome suffer from hypotonia, muscle weakness, and motor developmental delay and have increased fat mass combined with decreased muscle mass. Growth hormone improves body composition and motor development.

Ultrasound scans confirmed decreased muscle thickness in infants with Prader-Willi syndrome, which improved as result of growth hormone treatment. Muscle thickness was correlated to muscle strength and motor performance. Catch-up growth in muscle thickness was related to muscle use independent of growth hormone. (Read the full article)

Necrotizing enterocolitis is associated with high mortality and morbidity in premature infants. Anaerobic antimicrobial therapy has been associated with increased risk of intestinal strictures in a small randomized trial. Optimal antimicrobial therapy for necrotizing enterocolitis is unknown.

Anaerobic antimicrobial therapy was associated with increased risk of stricture formation. Infants with surgical necrotizing enterocolitis treated with anaerobic antimicrobial therapy had lower mortality. For infants with medical necrotizing enterocolitis, there was no added benefit associated with anaerobic antimicrobial therapy. (Read the full article)

Pediatric traumatic brain injury (TBI) contributes to impairments in functioning across multiple settings. Online family problem-solving therapy may be effective in reducing adolescent behavioral morbidity after TBI. However, less is known regarding maintenance of effects over time.

This large randomized clinical trial in adolescents with TBI is the only study to examine maintenance of treatment effects. Findings reveal that brief, online treatment may result in long-term improvements in child functioning, particularly among families of lower socioeconomic status. (Read the full article)

Parent refusal and delay of childhood vaccines has increased in recent years and is believed to cluster in communities. Such clustering could pose public health risks and barriers to achieving quality benchmarks for immunization coverage.

We found that underimmunization and vaccine refusal cluster geographically. Spatial scan analysis may be a useful tool to identify locations where clinicians may face challenges to achieving benchmarks for immunization coverage and that deserve special focus for interventions. (Read the full article)

Handheld echocardiography is a more portable and lower-cost alternative to standard echocardiography for rheumatic heart disease screening. Direct comparison of handheld echocardiography and auscultation for the detection of rheumatic heart disease has not been done previously.

Handheld echocardiography significantly improves detection of rheumatic heart disease compared with auscultation alone and may be a cost-effective screening strategy in developing countries. (Read the full article)

Functional capabilities in patients with spina bifida depend on the spinal level of the lesion and its type. Sociodemographic characteristics have been shown in other conditions to be an important additional influence on outcomes, making them important for risk adjustment.

Males, non-Hispanic blacks, and patients without private insurance have less favorable functional outcomes in spina bifida, and age also has an impact. These attributes need to be considered by clinicians and researchers and used in comparing care outcomes across clinic settings. (Read the full article)

Smoking has been found to increase the risk of some specific congenital anomalies; however, results remain inconsistent. Nicotine replacement therapy (NRT) is increasingly being used as for smoking cessation in pregnancy although little is known about its association with congenital anomalies.

Being prescribed NRT while pregnant was not associated with major congenital anomalies (MCA), except a small increase in respiratory anomalies (3/1000 births). This must be considered in context of the rarity of MCAs and higher morbidities in the NRT group. (Read the full article)

Concern of the risk of malignancy from ionizing radiation has prompted many to advocate for judicious use of computed tomography (CT) and as low as necessary radiation doses administered per scan. Recent analysis has shown a decline in CT utilization.

We identified decreases in CT utilization between 2004 and 2012 for the 10 most common diagnostic groups receiving CT. Decreases were typically associated with increases in alternate imaging modalities. We provide a possible reason for the decrease in CT utilization. (Read the full article)

Two prospective studies of children with septic arthritis have shown that the addition of dexamethasone to antibiotic therapy contributes to clinical and laboratory improvement. Nevertheless, the mainstay of treatment remains antibiotics alone.

This study, which was conducted outside a randomized controlled trial, demonstrates that children with septic arthritis treated early with a short course of adjuvant dexamethasone show earlier improvement in clinical and laboratory parameters than children treated with antibiotics alone. (Read the full article)

Children with cystic fibrosis demonstrate gas exchange abnormalities and increased respiratory loads during sleep independent of lung function, age, and BMI. Assessment of breathing patterns during sleep provides an opportunity for detection of early lung disease progression.

Children with cystic fibrosis demonstrated increased respiratory loads and gas exchange abnormalities during sleep compared with controls. Based on these findings, sleep assessment in this patient population can identify markers for the early detection of lung disease progression. (Read the full article)

Given the efforts to decrease the use of ionizing radiation in pediatric patients, there is significant variability in head computed tomography (CT) scan use in pediatric emergency departments for minor head trauma.

This study characterized variability in CT scan rates for all body regions in emergency department, observation, and inpatient encounters across 30 tertiary pediatric hospitals. Two-fold variation remained after case-mix adjustment, with higher volume hospitals having lower rates of CT scanning. (Read the full article)

"We can do better," Germany coach Silvia Neid concluded after her side joined France and Sweden in making it to the quarter-finals of the Olympic tournament in unspectacular fashion.

Sixteen design projects created by graphic design students at Pennsylvania College of Technology have been honored in the national Flux Student Design Competition.

The HUB-Robeson Galleries are proud to present "moments," an online thesis exhibition of photography by Zsuzsanna Nagy, a second-year master of fine arts student in photography.

Unable to host their senior capstone showcase as an on-campus celebration of their work with family and friends in attendance, graduating students in the Graphic Design undergraduate program in the Stuckeman School at Penn State are turning to Instagram to highlight their design work in a creative way to an even larger potential audience during the week of May 4-8.

The attempt by Congo and Rwanda to end the deadly conflict in eastern Congo by a secret presidential deal and military force is failing and must be changed fundamentally by the Kinshasa government and the international community.

Los conflictos en los países pequeños suelen agravarse debido a la indiferencia internacional. Sin embargo, en el caso de la República Centroafricana (RCA), el problema es ligeramente distinto. Hay una importante presencia internacional en este Estado, pero los actores principales han decidido mantenerse al margen y esperar en vez de intervenir activamente en la crisis.

Objectives. The aim of this study was to assess the safety of early oral switch (EOS) prior to 14 days for low-risk Staphylococcus aureus bacteremia (LR-SAB), which is the primary treatment strategy employed at our institution. Usually recommended therapy is 14 days of intravenous (IV) antibiotics.

Methods. All patients with SAB at our hospital were identified between 1 January 2014 and 31 December 2018. Those meeting low-risk criteria (healthcare-associated, no evidence of deep infection or demonstrated involvement of prosthetic material, and no further positive blood cultures after 72-hours) were included in the study. The primary outcome was occurrence of a SAB-related complication within 90 days.

Results. There were 469 SAB episodes during the study period, 100 (21%) of whom met inclusion criteria. EOS was performed in 84 patients. In this group, line infection was the source in 79%, methicillin-susceptible S. aureus caused 95% of SABs and 74% of patients received IV flucloxacillin. The median duration of IV and oral antibiotics in the EOS group was 5 (IQR 4-6) and 10 days (IQR 9-14), respectively. Seventy-one percent of patients received flucloxacillin as their EOS agent. Overall, 86% of oral step-down therapy was with beta-lactams. One patient (1%) undergoing EOS had SAB relapse within 90 days. No deaths attributable to SAB occurred within 90 days.

Conclusions. In this low MRSA prevalence LR-SAB cohort, EOS was associated with a low incidence of SAB-related complications. This was achieved with oral beta-lactam therapy in most patients. Larger prospective studies are needed to confirm these findings.

Leishmania major is the causative agent of cutaneous leishmaniasis (CL). No human vaccine is available for CL and current drug regimens present several drawbacks such as emerging resistance, severe toxicity, medium effectiveness, and/or high cost. Thus, the need for better treatment options against CL is a priority. In the present study, we validate the enzyme methionine aminopeptidase-1 (MetAP1), a metalloprotease that catalyzes the removal of N-terminal methionine from peptides and proteins, as a chemotherapeutic target against CL infection. The in vitro antileishmanial activity of eight novel MetAP1 inhibitors (OJT001-OJT008) were investigated. Three compounds OJT006, OJT007, and OJT008 demonstrated potent anti-proliferative effect in macrophages infected with L. major amastigotes and promastigotes at submicromolar concentrations, with no cytotoxicity against host cells. Importantly, the leishmanicidal effect was diminished by almost 10-fold in transgenic L. major promastigotes overexpressing MetAP1_LM in comparison to wild-type promastigotes. Furthermore, the in vivo activity of OJT006, OJT007, and OJT008 were investigated in L. major-infected BALB/c mice. In comparison to the control group, OJT008 significantly decreased footpad parasite load by 86%, and exhibited no toxicity against in treated mice. We propose MetAP1 inhibitor OJT008 as a potential chemotherapeutic candidate against CL infection caused by L. major infection.

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.

Objectives: Antibiotic combination therapy is used for severe infections caused by multidrug-resistant (MDR) Gram-negative bacteria. Yet, data of which combinations are most effective is lacking. This study aimed to evaluate the in vitro efficacy of polymyxin B in combination with 13 other antibiotics against four clinical strains of MDR Pseudomonas aeruginosa.

Methods: We evaluated the interactions of polymyxin B in combination with amikacin, aztreonam, cefepime, chloramphenicol, ciprofloxacin, fosfomycin, meropenem, minocycline, rifampicin, temocillin, thiamphenicol or trimethoprim by automated time-lapse microscopy using predefined cut-off values indicating inhibition of growth (≤10⁶ CFU/mL) at 24 h. Promising combinations were subsequently evaluated in static time-kill experiments.

Results: All strains were intermediate or resistant to polymyxin B, anti-pseudomonal β-lactams, ciprofloxacin and amikacin. Genes encoding β-lactamases (e.g., bla_PAO and bla_OXA-50) and mutations associated with permeability and efflux were detected in all strains. In the time-lapse microscopy experiments, positive interactions were found with 39 of 52 antibiotic combination/bacterial strain setups. Enhanced activity was found against all four strains with polymyxin B used in combination with aztreonam, cefepime, fosfomycin, minocycline, thiamphenicol and trimethoprim. Time kill experiments showed additive or synergistic activity with 27 of the 39 tested polymyxin B combinations, most frequently with aztreonam, cefepime, and meropenem.

Conclusion: Positive interactions were frequently found with the tested combinations, also against strains that harboured several resistance mechanisms to the single drugs and with antibiotics that are normally not active against P. aeruginosa. Further study is needed to explore the clinical utility of these combinations.

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.

Carbapenem-resistant Gram-negative pathogens are a critical public health threat and there is an urgent need for new treatments. Carbapenemases (β-lactamases able to inactivate carbapenems) have been identified in both serine β-lactamase (SBL) and metallo β-lactamase (MBL) families. The recent introduction of SBL carbapenemase-inhibitors has provided alternative therapeutic options. Unfortunately, there are no approved inhibitors of MBL-mediated carbapenem-resistance and treatment options for infections caused by MBL-producing Gram-negatives are limited. Here, we present ZN148, a zinc-chelating MBL-inhibitor capable of restoring the bactericidal effect of meropenem and in vitro clinical susceptibility to carbapenems in >98% of a large international collection of MBL-producing clinical Enterobacterales strains (n=234). Moreover, ZN148 was able to potentiate the effect of meropenem against NDM-1-producing Klebsiella pneumoniae in a murine neutropenic peritonitis model. ZN148 showed no inhibition of the human zinc-containing enzyme glyoxylase II at 500 μM and no acute toxicity was observed in an in vivo mouse model with cumulative dosages up to 128 mg/kg. Biochemical analysis showed a time-dependent inhibition of MBLs by ZN148 and removal of zinc ions from the active site. Addition of exogenous zinc after ZN148 exposure only restored MBL activity by ~30%, suggesting an irreversible mechanism of inhibition. Mass-spectrometry and molecular modelling indicated potential oxidation of the active site Cys221 residue. Overall, these results demonstrate the therapeutic potential of a ZN148-carbapenem combination against MBL-producing Gram-negative pathogens and that ZN148 is a highly promising MBL inhibitor, capable of operating in a functional space not presently filled by any clinically approved compound.