Use of Antidiabetic drugs during pregnancy among U.S. women with Livebirth deliveries in the Mini-Sentinel system

BACKGROUND: As the prevalence of diabetes mellitus increases in the population, the exposure to antidiabetic drugs (ADDs) during pregnancies is expected to grow, as has been seen over the last decade. The objective of this study was to estimate the prevalence of ADD use during pregnancy among women in the Mini-Sentinel Distributed Database (MSDD) who delivered a liveborn infant. METHODS: We identified qualifying livebirth pregnancies among women aged 10 to 54 years in the MSDD from 2001 to 2013. ADD use was estimated using outpatient pharmacy dispensing claims and days-supplied among three cohorts: all livebirth pregnancies, pregnancies among women with pre-existing diabetes, and pregnancies among women without prior ADD use. RESULTS: Among the 1.9 million pregnancies in the MSDD that resulted in a livebirth from 2001 to 2013, 4.4% were exposed to an ADD. Of the 15,606 pregnancies (0.8%) with pre-existing diabetes, 92.8% were also exposed during the pregnancy period. The most commonly used product in these pregnancies was insulin (75.6% of pregnancies). In contrast, in pregnancies of women without prior ADD use, the most commonly used products were glyburide and insulin, and most of these users were diagnosed with gestational diabetes. CONCLUSIONS: Patterns of ADD use during pregnancy described here, along with changes in disease incidence and management, highlight the importance of continuing surveillance of ADD utilization patterns and examining the safety and effectiveness of these products in pregnancy

Antiemetic use among pregnant women in the United States: the escalating use of ondansetron

PURPOSE: To examine ondansetron use in pregnancy in the context of other antiemetic use among a large insured United States population of women delivering live births. METHODS: We assessed ondansetron and other antiemetic use among pregnant women delivering live births between 2001 and 2015 in 15 data partners contributing data to the Mini-Sentinel Distributed Database. We identified live birth pregnancies using a validated algorithm, and all forms of ondansetron and other available antiemetics were identified using National Drug Codes or procedure codes. We assessed the prevalence of antiemetic use by trimester, calendar year, and formulation. RESULTS: In over 2.3 million pregnancies, the prevalence of ondansetron, promethazine, metoclopramide, or doxylamine/pyridoxine use anytime in pregnancy was 15.2, 10.3, 4.0, and 0.4%, respectively. Ondansetron use increased from \u3c1% of pregnancies in 2001 to 22.2% in 2014, with much of the increase attributable to oral ondansetron beginning in 2006. Promethazine and metoclopramide use increased modestly between 2001 (13.8%, 3.2%) and 2006 (16.0%, 6.0%) but decreased annually through 2014 (8.0%, 3.2%). Doxylamine/pyridoxine, approved for management of nausea and vomiting in pregnancy in 2013, was used in 1.8% of pregnancies in 2014. For all antiemetics, use was highest in the first trimester. CONCLUSIONS: We observed a marked increase in ondansetron use by study year, prescribed to nearly one-quarter of insured pregnant women in 2014, occurring in conjunction with decreased use of promethazine and metoclopramide. Given the widespread use of ondansetron in pregnancy, data establishing product efficacy and methodologically rigorous evaluation of post-marketing safety are needed

Nasal Iodophor Antiseptic vs Nasal Mupirocin Antibiotic in the Setting of Chlorhexidine Bathing to Prevent Infections in Adult ICUs: A Randomized Clinical Trial

IMPORTANCE: Universal nasal mupirocin plus chlorhexidine gluconate (CHG) bathing in intensive care units (ICUs) prevents methicillin-resistant Staphylococcus aureus (MRSA) infections and all-cause bloodstream infections. Antibiotic resistance to mupirocin has raised questions about whether an antiseptic could be advantageous for ICU decolonization. OBJECTIVE: To compare the effectiveness of iodophor vs mupirocin for universal ICU nasal decolonization in combination with CHG bathing. DESIGN, SETTING, AND PARTICIPANTS: Two-group noninferiority, pragmatic, cluster-randomized trial conducted in US community hospitals, all of which used mupirocin-CHG for universal decolonization in ICUs at baseline. Adult ICU patients in 137 randomized hospitals during baseline (May 1, 2015-April 30, 2017) and intervention (November 1, 2017-April 30, 2019) were included. INTERVENTION: Universal decolonization involving switching to iodophor-CHG (intervention) or continuing mupirocin-CHG (baseline). MAIN OUTCOMES AND MEASURES: ICU-attributable S aureus clinical cultures (primary outcome), MRSA clinical cultures, and all-cause bloodstream infections were evaluated using proportional hazard models to assess differences from baseline to intervention periods between the strategies. Results were also compared with a 2009-2011 trial of mupirocin-CHG vs no decolonization in the same hospital network. The prespecified noninferiority margin for the primary outcome was 10%. RESULTS: Among the 801 668 admissions in 233 ICUs, the participants\u27 mean (SD) age was 63.4 (17.2) years, 46.3% were female, and the mean (SD) ICU length of stay was 4.8 (4.7) days. Hazard ratios (HRs) for S aureus clinical isolates in the intervention vs baseline periods were 1.17 for iodophor-CHG (raw rate: 5.0 vs 4.3/1000 ICU-attributable days) and 0.99 for mupirocin-CHG (raw rate: 4.1 vs 4.0/1000 ICU-attributable days) (HR difference in differences significantly lower by 18.4% [95% CI, 10.7%-26.6%] for mupirocin-CHG, P \u3c .001). For MRSA clinical cultures, HRs were 1.13 for iodophor-CHG (raw rate: 2.3 vs 2.1/1000 ICU-attributable days) and 0.99 for mupirocin-CHG (raw rate: 2.0 vs 2.0/1000 ICU-attributable days) (HR difference in differences significantly lower by 14.1% [95% CI, 3.7%-25.5%] for mupirocin-CHG, P = .007). For all-pathogen bloodstream infections, HRs were 1.00 (2.7 vs 2.7/1000) for iodophor-CHG and 1.01 (2.6 vs 2.6/1000) for mupirocin-CHG (nonsignificant HR difference in differences, -0.9% [95% CI, -9.0% to 8.0%]; P = .84). Compared with the 2009-2011 trial, the 30-day relative reduction in hazards in the mupirocin-CHG group relative to no decolonization (2009-2011 trial) were as follows: S aureus clinical cultures (current trial: 48.1% [95% CI, 35.6%-60.1%]; 2009-2011 trial: 58.8% [95% CI, 47.5%-70.7%]) and bloodstream infection rates (current trial: 70.4% [95% CI, 62.9%-77.8%]; 2009-2011 trial: 60.1% [95% CI, 49.1%-70.7%]). CONCLUSIONS AND RELEVANCE: Nasal iodophor antiseptic did not meet criteria to be considered noninferior to nasal mupirocin antibiotic for the outcome of S aureus clinical cultures in adult ICU patients in the context of daily CHG bathing. In addition, the results were consistent with nasal iodophor being inferior to nasal mupirocin. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03140423

Daily Chlorhexidine Bathing in General Hospital Units – Results of the ABATE Infection Trial (Active BAThing to Eliminate Infection)

Abstract Background: Universal decolonization with daily chlorhexidine (CHG) bathing with and without nasal decolonization has significantly reduced positive MRSA clinical cultures and bloodstream infections in adult ICUs in several clinical trials. We evaluated whether decolonization was similarly effective in a lower risk hospitalized population. Methods: We conducted a 2 arm cluster-randomized trial involving a 1-year baseline period (April 2013–March 2014) and a 21-month intervention period (June 2014–February 2016). All noncritical care units in a hospital were assigned to the same strategy. These were (1) Routine Care: routine bathing product and frequency and (2) Decolonization: CHG for routine daily bathing (2% leave-on CHG) or showering (4% rinse-off CHG) for all patients plus mupirocin for 5 days for known MRSA. Universal ICU decolonization was in place in both arms by September 2013. Differences between the arms in the outcome rates between the baseline and intervention periods were assessed with proportional hazards models, using shared frailties to account for clustering by hospital. The primary analysis was as-randomized and unadjusted. Primary outcome was any MRSA or VRE clinical isolate attributable to the unit. Secondary outcome was all-cause bloodstream infections. Additional analyses adjusted for age, gender, race, Medicaid insurer, surgery, and comorbidities. Results: We randomized 53 hospitals in 15 states. There were 194 adult units with 189,616 admissions in the baseline period and 340,350 in the intervention period. Common unit types included mixed medical surgical (30%), cardiac (20%), step-down (11%), medical (10%), surgical (10%), and oncology (4%). There were no significant differences between arms in the relative hazards for intervention vs. baseline for either outcome (Table and Figure). Adjusted analyses yielded similar results. Conclusion: Universal daily CHG bathing or showering plus targeted mupirocin for MRSA+ patients in non-critical care units did not reduce the combination of positive MRSA and VRE clinical cultures or bloodstream infections due to all pathogens. Further analyses to assess for any differential effects in high-risk subpopulations will be important. Disclosures S. S. Huang, Sage Products: Receipt of contributed product, Conducting studies in which participating healthcare facilities are receiving contributed product (no contribution in submitted abstract), Participating healthcare facilities in my studies received contributed product; Xttrium Laboratories: Receipt of contributed product, Conducting studies in which participating healthcare facilities are receiving contributed product (no contribution in submitted abstract), Participating healthcare facilities in my studies received contributed product; Clorox: Receipt of contributed product, Conducting studies in which participating healthcare facilities are receiving contributed product (no contribution in submitted abstract), Participating healthcare facilities in my studies received contributed product; 3M: Receipt of contributed product, Conducting studies in which participating healthcare facilities are receiving contributed product (no contribution in submitted abstract), Participating healthcare facilities in my studies received contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; E. Septimus, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; K. Kleinman, Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Xttrium: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; 3M: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; J. Moody, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; J. Hickok, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; L. Heim, Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Xttrium: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; 3M: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; A. Gombosev, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; 3M: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; T. Avery, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; received research funds from Clorox, but Clorox has no role in the design K. Haffenreffer, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; receive research funds from Clorox, but Clorox has no role in the design; L. Shimelman, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; receive research funds from Clorox, but Clorox has no role in the design; M. K. Hayden, OpGen, Inc.: Receipt of donated laboratory services for project, Research support; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; R. A. Weinstein, Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; OpGen Inc.: Receipt of donated laboratory services for project, Research support; C. Spencer-Smith, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; R. E. Kaganov, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; M. V. Murphy, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; T. Forehand, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; J. Lankiewicz, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; M. H. Coady, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; received research funds from Clorox, but Clorox has no role in the design.; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; L. M. Portillo, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; J. Patel Sarup, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; J. Perlin, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; R. Platt, Clorox: Receipt of contributed product, Conducting clinical studies in which participating healthcare facilities are receiving contributed product; receive research funds from Clorox, but Clorox has no role in the design; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Xttrium: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed produc

Surveillance of Medication Use During Pregnancy in the Mini-Sentinel Program

OBJECTIVES: Mini-Sentinel is a pilot project sponsored by the U.S. Food and Drug Administration to create an active surveillance system to monitor the safety of FDA-regulated medical products. We assessed the capability of the Mini-Sentinel pilot to provide prevalence rates of medication use among pregnant women delivering a liveborn infant. METHODS: An algorithm was developed to identify pregnancies for a reusable analytic tool to be executed against the Mini-Sentinel Distributed Database. Diagnosis and procedure codes were used to identify women ages 10-54 years delivering a liveborn infant between April 2001 and December 2012. A comparison group of age- and date-matched nonpregnant women was identified. The analytic code was distributed to all 18 Mini-Sentinel data partners. The use of specific medications, selected because of concerns about their safe use during pregnancy, was identified from outpatient dispensing data. We determined the frequency of pregnancy episodes and nonpregnant episodes exposed to medications of interest, any time during the pregnant/matched nonpregnant period, and during each trimester. RESULTS: The analytic tool successfully identified 1,678,410 live birth deliveries meeting the eligibility criteria. The prevalence of use at any time during pregnancy was 0.38 % for angiotensin-converting enzyme inhibitors and 0.22 % for statins. For \u3c /=0.05 % of pregnancy episodes, the woman was dispensed warfarin, methotrexate, ribavirin, or mycophenolate. CONCLUSIONS: The analytic tool developed for this study can be used to assess the use of medications during pregnancy as safety issues arise, and is adaptable to include different medications, observation periods, pre-existing conditions, and enrollment criteria

Use of selective serotonin reuptake inhibitors (SSRIs) in women delivering liveborn infants and other women of child-bearing age within the U.S. Food and Drug Administration\u27s Mini-Sentinel program

This study was conducted in order to assess the prevalence of use of selective serotonin reuptake inhibitors (SSRIs) among pregnant women delivering a liveborn infant in the USA. A retrospective study was conducted using the automated databases of 15 health-care systems participating in the Mini-Sentinel program. Diagnosis and procedure codes were used to identify women ages 10 to 54 years delivering a liveborn infant between April 2001 and December 2013. A comparison group of age- and date-matched women without live births was identified. The frequency of use of SSRIs was identified from outpatient dispensing data. Among the 1,895,519 liveborn deliveries, 113,689 women (6.0 %) were exposed to an SSRI during pregnancy during the period 2001-2013; 5.4 % were exposed to an SSRI during 2013. During the corresponding time period, 10.5 % of the age- and date-matched cohort of women without live births was exposed to an SSRI, with 10.1 % exposed to an SSRI during 2013. The most common agents dispensed during pregnancy were sertraline (n = 48,678), fluoxetine (n = 28,983), and citalopram (n = 20,591). Among those women exposed to an SSRI during pregnancy, 53.8 % had a diagnosis of depression and 37.3 % had a diagnosis of an anxiety disorder during pregnancy or within 180 days prior to pregnancy. Our finding that 6 % of women with live births were prescribed SSRIs during pregnancy highlights the importance of understanding the differential effects of these medications and other therapeutic options on the developing fetus and on the pregnant women

Chlorhexidine and Mupirocin Susceptibility of Methicillin-Resistant Staphylococcus aureus Isolates in the REDUCE-MRSA Trial

Whether targeted or universal decolonization strategies for the control of methicillin-resistant Staphylococcus aureus (MRSA) select for resistance to decolonizing agents is unresolved. The REDUCE-MRSA trial (ClinicalTrials registration no. NCT00980980) provided an opportunity to investigate this question. REDUCE-MRSA was a 3-arm, cluster-randomized trial of either screening and isolation without decolonization, targeted decolonization with chlorhexidine and mupirocin, or universal decolonization without screening to prevent MRSA infection in intensive-care unit (ICU) patients. Isolates from the baseline and intervention periods were collected and tested for susceptibility to chlorhexidine gluconate (CHG) by microtiter dilution; mupirocin susceptibility was tested by Etest. The presence of the qacA or qacB gene was determined by PCR and DNA sequence analysis. A total of 3,173 isolates were analyzed; 2 were nonsusceptible to CHG (MICs, 8 μg/ml), and 5/814 (0.6%) carried qacA or qacB. At baseline, 7.1% of MRSA isolates expressed low-level mupirocin resistance, and 7.5% expressed high-level mupirocin resistance. In a mixed-effects generalized logistic regression model, the odds of mupirocin resistance among clinical MRSA isolates or MRSA isolates acquired in an ICU in intervention versus baseline periods did not differ across arms, although estimates were imprecise due to small numbers. Reduced susceptibility to chlorhexidine and carriage of qacA or qacB were rare among MRSA isolates in the REDUCE-MRSA trial. The odds of mupirocin resistance were no different in the intervention versus baseline periods across arms, but the confidence limits were broad, and the results should be interpreted with caution

Chlorhexidine and Mupirocin Susceptibility of Methicillin-Resistant Staphylococcus aureus Isolates in the REDUCE-MRSA Trial.

Whether targeted or universal decolonization strategies for the control of methicillin-resistant Staphylococcus aureus (MRSA) select for resistance to decolonizing agents is unresolved. The REDUCE-MRSA trial (ClinicalTrials registration no. NCT00980980) provided an opportunity to investigate this question. REDUCE-MRSA was a 3-arm, cluster-randomized trial of either screening and isolation without decolonization, targeted decolonization with chlorhexidine and mupirocin, or universal decolonization without screening to prevent MRSA infection in intensive-care unit (ICU) patients. Isolates from the baseline and intervention periods were collected and tested for susceptibility to chlorhexidine gluconate (CHG) by microtiter dilution; mupirocin susceptibility was tested by Etest. The presence of the qacA or qacB gene was determined by PCR and DNA sequence analysis. A total of 3,173 isolates were analyzed; 2 were nonsusceptible to CHG (MICs, 8 μg/ml), and 5/814 (0.6%) carried qacA or qacB At baseline, 7.1% of MRSA isolates expressed low-level mupirocin resistance, and 7.5% expressed high-level mupirocin resistance. In a mixed-effects generalized logistic regression model, the odds of mupirocin resistance among clinical MRSA isolates or MRSA isolates acquired in an ICU in intervention versus baseline periods did not differ across arms, although estimates were imprecise due to small numbers. Reduced susceptibility to chlorhexidine and carriage of qacA or qacB were rare among MRSA isolates in the REDUCE-MRSA trial. The odds of mupirocin resistance were no different in the intervention versus baseline periods across arms, but the confidence limits were broad, and the results should be interpreted with caution

Chlorhexidine and Mupirocin Susceptibility of Methicillin-Resistant Staphylococcus aureus Isolates in the REDUCE-MRSA Trial.

Whether targeted or universal decolonization strategies for the control of methicillin-resistant Staphylococcus aureus (MRSA) select for resistance to decolonizing agents is unresolved. The REDUCE-MRSA trial (ClinicalTrials registration no. NCT00980980) provided an opportunity to investigate this question. REDUCE-MRSA was a 3-arm, cluster-randomized trial of either screening and isolation without decolonization, targeted decolonization with chlorhexidine and mupirocin, or universal decolonization without screening to prevent MRSA infection in intensive-care unit (ICU) patients. Isolates from the baseline and intervention periods were collected and tested for susceptibility to chlorhexidine gluconate (CHG) by microtiter dilution; mupirocin susceptibility was tested by Etest. The presence of the qacA or qacB gene was determined by PCR and DNA sequence analysis. A total of 3,173 isolates were analyzed; 2 were nonsusceptible to CHG (MICs, 8 μg/ml), and 5/814 (0.6%) carried qacA or qacB At baseline, 7.1% of MRSA isolates expressed low-level mupirocin resistance, and 7.5% expressed high-level mupirocin resistance. In a mixed-effects generalized logistic regression model, the odds of mupirocin resistance among clinical MRSA isolates or MRSA isolates acquired in an ICU in intervention versus baseline periods did not differ across arms, although estimates were imprecise due to small numbers. Reduced susceptibility to chlorhexidine and carriage of qacA or qacB were rare among MRSA isolates in the REDUCE-MRSA trial. The odds of mupirocin resistance were no different in the intervention versus baseline periods across arms, but the confidence limits were broad, and the results should be interpreted with caution