Outcomes of severely injured pregnant trauma patients: a multicenter analysis.

Nearly 10% of pregnant women suffer traumatic injury. Clinical outcomes for pregnant trauma patients (PTPs) with severe injuries have not been well studied. We sought to describe outcomes for PTPs presenting with severe injuries, hypothesizing that PTPs with severe injuries will have higher rates of complications and mortality compared to less injured PTPs. A post-hoc analysis of a multi-institutional retrospective study at 12 Level-I/II trauma centers was performed. Patients were stratified into severely injured (injury severity score [ISS] > 15) and not severely injured (ISS < 15) and compared with bivariate analyses. From 950 patients, 32 (3.4%) had severe injuries. Compared to non-severely injured PTPs, severely injured PTPs were of similar maternal age but had younger gestational age (21 vs 26 weeks, p = 0.009). Penetrating trauma was more common in the severely injured cohort (15.6% vs 1.4%, p < 0.001). The severely injured cohort more often underwent an operation (68.8% vs 3.8%, p < 0.001), including a hysterectomy (6.3% vs 0.3%, p < 0.001). The severely injured group had higher rates of complications (34.4% vs 0.9%, p < 0.001), mortality (15.6% vs 0.1%, p < 0.001), a higher rate of fetal delivery (37.5% vs. 6.0%, p < 0.001) and resuscitative hysterotomy (9.4% vs. 0%, p < 0.001). Only approximately 3% of PTPs were severely injured. However, severely injured PTPs had a nearly 40% rate of fetal delivery as well as increased complications and mortality. This included a resuscitative hysterotomy rate of nearly 10%. Significant vigilance must remain when caring for this population.

Delayed rib plating and lung herniation repair in a traumatic chest injury after thoracotomy: A case report.

INTRODUCTION AND IMPORTANCE: Lung herniation following trauma is a rare occurrence, and consensus on optimal surgical repair techniques remains limited. While small herniations may resolve without surgery, intervention becomes necessary in cases of unsuccessful non-operative management or concurrent rib fracture stabilization. Mesh application in repair poses a dilemma, often providing physical support but raising infection concerns, particularly in trauma scenarios with delayed closure. Surgical stabilization of rib fractures, employing hardware similar to orthopedic procedures, may necessitate prophylactic antibiotics, though empirical evidence supporting routine use is scant. Polytrauma patients often resort to delayed chest closure techniques during methodical surgical planning, but these carry potential consequences compared to immediate closure. CASE PRESENTATION: Presented is a case involving a patient in a motorcycle collision sustaining multiple injuries, necessitating a massive transfusion protocol, multiple surgeries, including delayed chest closure, and eventual surgical rib fixation four days post-injury. During rib stabilization, exacerbation of traumatic lung herniation mandated mesh repair, prompting the cautious use of prophylactic vancomycin powder to mitigate infection risks. DISCUSSION: A review of the literature revealed a scarcity of similar cases, particularly those involving lung herniation with delayed chest closure, the use of prophylactic antibiotics and mesh in polytrauma. CONCLUSION: This case underscores the lack of depth of comprehensive research guiding surgical decisions concerning lung herniation and the prophylactic use of vancomycin powder in trauma patients.

Predictors of fetal delivery in pregnant trauma patients: A multicenter study.

BACKGROUND: Pregnant trauma patients (PTPs) undergo observation and fetal monitoring following trauma due to possible fetal delivery (FD) or adverse outcome. There is a paucity of data on PTP outcomes, especially related to risk factors for FD. We aimed to identify predictors of posttraumatic FD in potentially viable pregnancies. METHODS: All PTPs (≥18 years) with ≥24-weeks gestational age were included in this multicenter retrospective study at 12 Level-I and II trauma centers between 2016 and 2021. Pregnant trauma patients who underwent FD ((+) FD) were compared to those who did not deliver ((-) FD) during the index hospitalization. Univariate analyses and multivariable logistic regression were performed to identify predictors of FD. RESULTS: Of 591 PTPs, 63 (10.7%) underwent FD, with 4 (6.3%) maternal deaths. The (+) FD group was similar in maternal age (27 vs. 28 years, p = 0.310) but had older gestational age (37 vs. 30 weeks, p < 0.001) and higher mean injury severity score (7.0 vs. 1.5, p < 0.001) compared with the (-) FD group. The (+) FD group had higher rates of vaginal bleeding (6.3% vs. 1.1%, p = 0.002), uterine contractions (46% vs. 23.5%, p < 0.001), and abnormal fetal heart tracing (54.7% vs. 14.6%, p < 0.001). On multivariate analysis, independent predictors for (+) FD included abdominal injury (odds ratio [OR], 4.07; confidence interval [CI], 1.11-15.02; p = 0.035), gestational age (OR, 1.68 per week ≥24 weeks; CI, 1.44-1.95; p < 0.001), abnormal FHT (OR, 12.72; CI, 5.19-31.17; p < 0.001), and premature rupture of membranes (OR, 35.97; CI, 7.28-177.74; p < 0.001). CONCLUSION: The FD rate was approximately 10% for PTPs with viable fetal gestational age. Independent risk factors for (+) FD included maternal and fetal factors, many of which are available on initial trauma bay evaluation. These risk factors may help predict FD in the trauma setting and shape future guidelines regarding the recommended observation of PTPs. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Significant variation in computed tomography imaging of pregnant trauma patients: a retrospective multicenter study.

PURPOSE: Following motor vehicle collisions (MVCs), patients often undergo extensive computed tomography (CT) imaging. However, pregnant trauma patients (PTPs) represent a unique population where the risk of fetal radiation may supersede the benefits of liberal CT imaging. This study sought to evaluate imaging practices for PTPs, hypothesizing variability in CT imaging among trauma centers. If demonstrated, this might suggest the need to develop specific guidelines to standardize practice. METHODS: A multicenter retrospective study (2016-2021) was performed at 12 Level-I/II trauma centers. Adult (≥18 years old) PTPs involved in MVCs were included, with no patients excluded. The primary outcome was the frequency of CT. Chi-square tests were used to compare categorical variables, and ANOVA was used to compare the means of normally distributed continuous variables. RESULTS: A total of 729 PTPs sustained MVCs (73% at high speed of ≥ 25 miles per hour). Most patients were mildly injured but a small variation of injury severity score (range 1.1-4.6, p < 0.001) among centers was observed. There was a variation of imaging rates for CT head (range 11.8-62.5%, p < 0.001), cervical spine (11.8-75%, p < 0.001), chest (4.4-50.2%, p < 0.001), and abdomen/pelvis (0-57.3%, p < 0.001). In high-speed MVCs, there was variation for CT head (12.5-64.3%, p < 0.001), cervical spine (16.7-75%, p < 0.001), chest (5.9-83.3%, p < 0.001), and abdomen/pelvis (0-60%, p < 0.001). There was no difference in mortality (0-2.9%, p =0.19). CONCLUSION: Significant variability of CT imaging in PTPs after MVCs was demonstrated across 12 trauma centers, supporting the need for standardization of CT imaging for PTPs to reduce unnecessary radiation exposure while ensuring optimal injury identification is achieved.

Victims of Violence, How a Trauma Center and Family Justice Center Can Provide Continued Care After Initial Hospitalization.

BACKGROUND: Intentional injuries are the second leading cause of death in the U.S. between the ages of 1 and 44. Each traumatic event is approached best with a multiagency and multidisciplinary approach. Family Justice Centers (FJCs) are structured as one-stop centers for victims of all forms of violence to provide services. OBJECTIVE: The purpose of this study is to describe trauma patients evaluated in an FJC and determine the effect of the referrals on injury-related hospital recidivism. METHOD: This is a cross-sectional descriptive study of traumatically injured patients that were evaluated in an adult level II trauma center for 3 years and were referred to Ventura County's FJC. RESULTS: There were 415 trauma admissions for intentional injuries, which accounted for 10.4% of the total trauma-related hospital admissions. Of these patients, 203 (49%) were evaluated in Ventura County's FJC. The remaining 212 (51%) had an open judicial case, thus, were not processed through the FJC due to conflict of interest. The mechanisms of injuries of patients that were evaluated at the FJC (N = 203) were mostly assaults (83%). Majority of the patients were of the Hispanic race (70%), males (69%), English speaking (77%), and aged 18-59 (84%). 573 individual services were provided to these patients. The patients evaluated through the FJC (N = 203) had zero recidivism, while those with open cases had a 1% recidivism rate (P = NS). CONCLUSION: By collaborating with FJCs, trauma center outcomes contribute to a pathway for healing and may prevent future acts of intentional injuries.

Outcomes for advanced aged (35 and older) versus younger aged pregnant trauma patients: A multicenter study.

BACKGROUND: Effects of advanced maternal age (AMA) pregnancies (defined as ≥35 years) on pregnant trauma patients (PTPs) are unknown. This study compared AMA versus younger PTPs, hypothesizing AMA PTPs have increased risk of fetal delivery (FD). METHODS: A retrospective (2016-2021) multicenter study included all PTPs. Multivariable logistic regression was used to evaluate risk of FD after trauma. RESULTS: A total of 950 PTPs were included. Both cohorts had similar gestational age and injury severity scores. The AMA group had increased injuries to the pancreas, bladder, and stomach (p < 0.05). There was no difference in rate or associated risk of FD between cohorts (5.3% vs. 11.4%; OR 0.59, CI 0.19-1.88, p > 0.05). CONCLUSION: Compared to their younger counterparts, some intra-abdominal injuries (pancreas, bladder, and stomach) were more common among AMA PTPs. However, there was no difference in rate or associated risk of FD in AMA PTPs, thus they do not require increased observation.

The Effect of 2019 Coronavirus Stay-at-Home Order on Geriatric Trauma Patients in Southern California.

BACKGROUND: California issued stay-at-home (SAH) orders to mitigate COVID-19 spread. Previous studies demonstrated a shift in mechanisms of injuries (MOIs) and decreased length of stay (LOS) for the general trauma population after SAH orders. This study aimed to evaluate the effects of SAH orders on geriatric trauma patients (GTPs), hypothesizing decreased motor vehicle collisions (MVCs) and LOS. METHODS: A post-hoc analysis of GTPs (≥65 years old) from 11 level-I/II trauma centers was performed, stratifying patients into 3 groups: before SAH (1/1/2020-3/18/2020) (PRE), after SAH (3/19/2020-6/30/2020) (POST), and a historical control (3/19/2019-6/30/2019) (CONTROL). Bivariate comparisons were performed. RESULTS: 5486 GTPs were included (PRE-1756; POST-1706; CONTROL-2024). POST had a decreased rate of MVCs (7.6% vs 10.6%, P = .001; vs 11.9%, P < .001) and pedestrian struck (3.4% vs 5.8%, P = .001; vs 5.2%, P = .006) compared with PRE and CONTROL. Other mechanisms of injury, LOS, mortality, and operations performed were similar between cohorts. However, POST had a lower rate of discharge to skilled nursing facility (SNF) (20% vs 24.5%, P = .001; and 20% vs 24.4%, P = .001). CONCLUSION: This retrospective multicenter study demonstrated lower rates of MVCs and pedestrian struck for GTPs, which may be explained by decreased population movement as a result of SAH orders. Contrary to previous studies on the generalized adult population, no differences in other MOIs and LOS were observed after SAH orders. However, there was a lower rate of discharge to SNF, which may be related to a lack of resources due to the COVID-19 pandemic, and thus potentially negatively impacted recovery of GTPs.Keywords.

Examining the Domestic Violence Crisis in Ventura County in the Wake of the COVID-19 Pandemic.

BACKGROUND: Domestic violence (DV) worsened during COVID-19 and Family Justice Centers (FJCs) were, even more so than before, a critical part of providing services to DV victims. This study characterizes the clinical and sociodemographic features of the clients that come to the Ventura County FJC (VCFJC) and examines the effect of COVID-19, thus informing awareness of services available to victims of DV. METHODS: This was a retrospective cohort study utilizing the VCFJC database from 2019 to 2021. All client data normally collected was studied. A comparison of pre-COVID and post-COVID data was also conducted. RESULTS: There were 3488 client entries. Clients were mostly female (79% [2755]; n = 3488), aged 25-40 (31.73% [1106]; n = 3448), white/Caucasian (44.42% [1531]; n = 3448) or Hispanic/Latinx (42.41% [1462]; n = 3448). Clients most often requested restraining orders (72.41% [2496]; n = 3448), and most commonly reported DV [physical] (47.90% [1651]; n = 3448). Most health-insured clients were covered by MediCal (45.06% [1231]; n = 2732). Pre- and post-COVID analysis showed the highest increases in DV [physical] (odds ratio = 1.26, P < .0007) and stalking/harassment (odds ratio = 2.45, P < .0007), and decreases in all Initial Service Request categories except one. DISCUSSION: In serving clients affected by DV, FJCs are an important service for health care providers to be aware of. Post-COVID, clients reported DV and stalking/harassment at much higher percentages, which is consistent with national studies on the pandemic. The most alarming finding was the steep decrease in Initial Service Requests.Conclusion: This study shows the importance of collaboration and awareness of services, especially in a world of COVID-19.

The Role of the US Trauma Centers in Older Adult Fall Prevention: A National Survey.

INTRODUCTION: Approximately 27.5% of adults 65 and older fall each year, over 3 million are treated in an emergency department, and 32 000 die. The American College of Surgeons and its Committee on Trauma (ACSCOT) have urged trauma centers (TCs) to screen for fall risk, but information on the role of TC in this opportunity for prevention is largely unknown. METHODS: A 29-item survey was developed by an ACSCOT Injury Prevention and Control Committee, Older Adult Falls workgroup, and emailed to 1000 trauma directors of the National Trauma Data Bank using Qualtrics. US TCs were surveyed regarding fall prevention, screening, intervention, and hospital discharge practices. Data collected and analyzed included respondent's role, location, population density, state designation or American College of Surgeons (ACS) level, if teaching facility, and patient population. RESULTS: Of the 266 (27%) respondents, 71% of TCs include fall prevention as part of their mission, but only 16% of TCs use fall risk screening tools. There was no significant difference between geographic location or ACS level. The number of prevention resources (F = 31.58, P < .0001) followed by the presence of a formal screening tool (F = 21.47, P < .0001) best predicted the presence of a fall prevention program. CONCLUSION: Older adult falls remain a major injury risk and injury prevention opportunity. The majority of TCs surveyed include prevention of older adult falls as part of their mission, but few incorporate the components of a fall prevention program. Development of best practices and requiring TCs to screen and offer interventions may prevent falls.

Association of socioeconomic status with the clinical management and outcomes in young patients (≤35 years) diagnosed with breast cancer: A retrospective analysis.

Background: Very young breast cancer at 35 years or younger is rare and tends to be aggressive. The management of very young breast cancer should be equally aggressive, and early diagnosis is critical. We hypothesized that socioeconomic status (SES) is associated with how very young breast cancer (VYBC) patients are diagnosed and treated in our community. Methods: We retrospectively analyzed a database for invasive breast cancer or ductal carcinoma in-situ (DCIS) diagnosed ≤35 years old (VYBC) from both a government-run county hospital (CH) and a neighboring private hospital (PH) for 82 months. Inclusion criteria composed of female patients diagnosed with invasive breast cancer and DCIS at ≤35 years of age at diagnosis were examined in our analysis. Patient diagnoses and severity, treatment, and outcomes were compared between the two facilities. The methods are consistent with the STROCSS guidelines. Results: The incidence of VYBC was a significantly higher percentage of new breast cancers diagnosed in the CH at 5.4% as compared to the PH at 1.9% (OR: 2.94; p < 0.001). CH had a significantly higher proportion of Medicaid payers (73% CH vs. 21% PH, p < 0.001). Mean time from patient's initial symptoms until a tissue diagnosis was significantly longer at the county hospital at 9.6 months vs 2.1 months at the private hospital (p < 0.01). Stage I tumors were only found in 13% of county hospital patients versus 67% at the private hospital (p < 0.001). Approximately 63% of the patients at the government-run county facility had a relative delay in diagnosis, contributing to higher stage at presentation. The rate of mastectomy surgery was high at both institutions: CH 83% vs. PH 76% (p = NS). Discussion: The results of our study suggest a significant healthcare difference between county and private hospital systems among very young breast cancer patients. Patients at the county hospital system had a longer delay to diagnosis leading to worse outcomes. This difference may be a reflection of barriers in health literacy or access to medical care.

Convergent Alterations of a Protein Hub Produce Divergent Effects within a Binding Site.

Progress in tumor sequencing and cancer databases has created an enormous amount of information that scientists struggle to sift through. While several research groups have created computational methods to analyze these databases, much work still remains in distinguishing key implications of pathogenic mutations. Here, we describe an approach to identify and evaluate somatic cancer mutations of WD40 repeat protein 5 (WDR5), a chromatin-associated protein hub. This multitasking protein maintains the functional integrity of large multi-subunit enzymatic complexes of the six human SET1 methyltransferases. Remarkably, the somatic cancer mutations of WDR5 preferentially distribute within and around an essential cavity, which hosts the WDR5 interaction (Win) binding site. Hence, we assessed the real-time binding kinetics of the interactions of key clustered WDR5 mutants with the Win motif peptide ligands of the SET1 family members (SET1Win). Our measurements highlight that this subset of mutants exhibits divergent perturbations in the kinetics and strength of interactions not only relative to those of the native WDR5 but also among various SET1Win ligands. These outcomes could form a fundamental basis for future drug discovery and other developments in medical biotechnology.

Adolescent Trauma During the COVID Pandemic: Just Like Adults, Children, or Someone Else?

COVID-19 stay-at-home (SAH) orders were impactful on adolescence, when social interactions affect development. This has the potential to change adolescent trauma. A post-hoc multicenter retrospective analysis of adolescent (13-17 years-old) trauma patients (ATPs) at 11 trauma centers was performed. Patients were divided into 3 groups based on injury date: historical control (CONTROL:3/19/2019-6/30/2019, before SAH (PRE:1/1/2020-3/18/2020), and after SAH (POST:3/19/2020-6/30/2020). The POST group was compared to both PRE and CONTROL groups in separate analyses. 726 ATPs were identified across the 3 time periods. POST had a similar penetrating trauma rate compared to both PRE (15.8% vs 13.8%, P = .56) and CONTROL (15.8% vs 14.5%, P = .69). POST also had a similar rate of suicide attempts compared to both PRE (1.2% vs 1.5%, P = .83) and CONTROL (1.2% vs 2.1%, P = .43). However, POST had a higher rate of drug positivity compared to CONTROL (28.6% vs 20.6%, P = .032), but was similar in all other comparisons of alcohol and drugs to PRE and POST periods (all P > .05). Hence ATPs were affected differently than adults and children, as they had a similar rate of penetrating trauma, suicide attempts, and alcohol positivity after SAH orders. However, they had increased drug positivity compared to the CONTROL, but not PRE group.

Decreased hospital length of stay and intensive care unit admissions for non-COVID blunt trauma patients during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic overwhelmed hospitals, forcing adjustments including discharging patients earlier and limiting intensive care unit (ICU) utilization. This study aimed to evaluate ICU admissions and length of stay (LOS) for blunt trauma patients (BTPs). METHODS: A retrospective review of COVID (3/19/20-6/30/20) versus pre-COVID (3/19/19-6/30/19) BTPs at eleven trauma centers was performed. Multivariable analysis was used to identify risk factors for ICU admission. RESULTS: 12,744 BTPs were included (6942 pre-COVID vs. 5802 COVID). The COVID cohort had decreased mean LOS (3.9 vs. 4.4 days, p = 0.029), ICU LOS (0.9 vs. 1.1 days, p < 0.001), and rate of ICU admission (22.3% vs. 24.9%, p = 0.001) with no increase in complications or mortality compared to the pre-COVID cohort (all p > 0.05). On multivariable analysis, the COVID period was associated with decreased risk of ICU admission (OR = 0.82, CI 0.75-0.90, p < 0.001). CONCLUSIONS: BTPs had decreased LOS and associated risk of ICU admission during COVID, with no corresponding increase in complications or mortality.

Understanding the makeup of a growing field: A committee on trauma survey of the national network of hospital-based violence intervention programs.

BACKGROUND: Among Hospital Based Violence Intervention programs (HVIPs), little is known about variation in services provided, funding sources, or populations served. STUDY DESIGN: Twenty-eight member programs of Health Alliance for Violence Intervention participated in a survey administered by the American College of Surgeons Committee on Trauma. Questions were quantitative and qualitative. For qualitative analysis, questions pertaining to the domains were assessed for common themes and assessed across all subject domains. RESULTS: All programs enroll patients injured by community violence, some by intimate partner violence (IPV), trafficking, and rarely by child or elder abuse. Programs with more funding (≥$300,000 per year) were more likely federally, state, or city funded. Lower funded programs (≤$300,000 per year) were funded by foundations or philanthropy. In both qualitative and quantitative analysis, barriers to starting or sustaining HVIPs included funding, and lack of risk reduction and mental health resources. Successful programs had stable funding, adequate staffing, and buy in from hospitals and staff. CONCLUSION: HVIPs serve diverse populations in variable models. There is opportunity to expand the reach of HVIPs, and the experience if existing programs is an invaluable resource.

Effects of the COVID-19 pandemic on pediatric trauma in Southern California.

PURPOSE: The COVID-19 pandemic resulted in increased penetrating trauma and decreased length of stay (LOS) amongst the adult trauma population, findings important for resource allocation. Studies regarding the pediatric trauma population are sparse and mostly single-center. This multicenter study examined pediatric trauma patients, hypothesizing increased penetrating trauma and decreased LOS after the 3/19/2020 stay-at-home (SAH) orders. METHODS: A multicenter retrospective analysis of trauma patients ≤ 17 years old presenting to 11 centers in California was performed. Demographic data, injury characteristics, and outcomes were collected. Patients were divided into three groups based on injury date: 3/19/2019-6/30/2019 (CONTROL), 1/1/2020-3/18/2020 (PRE), 3/19/2020-6/30/2020 (POST). POST was compared to PRE and CONTROL in separate analyses. RESULTS: 1677 patients were identified across all time periods (CONTROL: 631, PRE: 479, POST: 567). POST penetrating trauma rates were not significantly different compared to both PRE (11.3 vs. 9.0%, p = 0.219) and CONTROL (11.3 vs. 8.2%, p = 0.075), respectively. POST had a shorter mean LOS compared to PRE (2.4 vs. 3.3 days, p = 0.002) and CONTROL (2.4 vs. 3.4 days, p = 0.002). POST was also not significantly different than either group regarding intensive care unit (ICU) LOS, ventilator days, and mortality (all p > 0.05). CONCLUSIONS: This multicenter retrospective study demonstrated no difference in penetrating trauma rates among pediatric patients after SAH orders but did identify a shorter LOS.

Sphingosine kinase 2 is essential for remyelination following cuprizone intoxication.

Therapeutics that promote oligodendrocyte survival and remyelination are needed to restore neurological function in demyelinating diseases. Sphingosine 1-phosphate (S1P) is an essential lipid metabolite that signals through five G-protein coupled receptors. S1P receptor agonists such as Fingolimod are valuable immunosuppressants used to treat multiple sclerosis, and promote oligodendrocyte survival. However, the role for endogenous S1P, synthesized by the enzyme sphingosine kinase 2 (SphK2), in oligodendrocyte survival and myelination has not been established. This study investigated the requirement for SphK2 in oligodendrocyte survival and remyelination using the cuprizone mouse model of acute demyelination, followed by spontaneous remyelination. Oligodendrocyte density did not differ between untreated wild-type (WT) and SphK2 knockout (SphK2-/- ) mice. However, cuprizone treatment caused significantly greater loss of mature oligodendrocytes in SphK2-/- compared to WT mice. Following cuprizone withdrawal, spontaneous remyelination occurred in WT but not SphK2-/- mice, even though progenitor and mature oligodendrocyte density increased in both genotypes. Levels of cytotoxic sphingosine and ceramide were higher in the corpus callosum of SphK2-/- mice, and in contrast to WT mice, did not decline following cuprizone withdrawal in SphK2-/- mice. We also observed a significant reduction in myelin thickness with aging in SphK2-/- compared to WT mice. These results provide the first evidence that SphK2, the dominant enzyme catalyzing S1P synthesis in the adult brain, is essential for remyelination following a demyelinating insult and myelin maintenance with aging. We propose that persistently high levels of sphingosine and ceramide, a direct consequence of SphK2 deficiency, may block remyelination.

Complex effects of macrolide venturicidins on bacterial F-ATPases likely contribute to their action as antibiotic adjuvants.

Bacterial energy metabolism is now recognized as a critical factor for the efficacy of antibiotics. The F-type ATPase/ATP synthase (FOF1) is a central player in cellular bioenergetics of bacteria and eukaryotes, and its potential as a selective antibiotic target has been confirmed by the success of bedaquiline in combatting multidrug-resistant tuberculosis. Venturicidin macrolides were initially identified for their antifungal properties and were found to specifically inhibit FOF1 of eukaryotes and bacteria. Venturicidins alone are not effective antibacterials but recently were found to have adjuvant activity, potentiating the efficacy of aminoglycoside antibiotics against several species of resistant bacteria. Here we discovered more complex effects of venturicidins on the ATPase activity of FOF1 in bacterial membranes from Escherichia coli and Pseudomonas aeruginosa. Our major finding is that higher concentrations of venturicidin induce time- and ATP-dependent decoupling of F1-ATPase activity from the venturicidin-inhibited, proton-transporting FO complex. This dysregulated ATPase activity is likely to be a key factor in the depletion of cellular ATP induced by venturicidins in prior studies with P. aeruginosa and Staphylococcus aureus. Further studies of how this functional decoupling occurs could guide development of new antibiotics and/or adjuvants that target the F-type ATPase/ATP synthase.