Are Some Antibiotics More Likely to Trigger Serious Cutaneous Adverse Drug Reactions?
BACKGROUND AND PURPOSE:
Antibiotics are one of the most common triggers of serious cutaneous adverse drug reactions (cADRs), a group of severe drug hypersensitivity reactions
It is not clear whether certain classes of antibiotics are more likely to be implicated in cADRs
Lee et al. (JAMA, 2024) explored the risk of serious cADRs associated with commonly prescribed oral antibiotics, and characterized outcomes of hospitalized patients
METHODS:
Nested case-control study
Population
≥66 years
Received ≥1 oral antibiotic between 2002 and 2022 in Ontario, Canada
Cases: individuals with an emergency department (ED) visit or hospitalization for serious cADRs within 60 days of the prescription
Exposures
Oral antibiotic class
Study design
Each case patient was matched with up to 4 controls (individuals without an ED visit for cADRs)
Conditional logistic regression was used, using macrolides as the reference group
Compared to macrolides, the following were most strongly associated with serious cADRs
Sulfonamide antibiotics: adjusted Odds Ratio (aOR) 2.9 (95% CI, 2.7 to 3.1)
Cephalosporins: aOR 2.6 (95% CI, 2.5 to 2.8)
There was also a significant, but less strong, association between the following and serious cADRs
Nitrofurantoin: aOR 2.2 (95% CI, 2.1 to 2.4)
Penicillins: aOR 1.4 (95% CI, 1.3 to 1.5)
Fluoroquinolones: aOR 1.3 (95% CI, 1.2 to 1.4)
The crude rate of ED visits or hospitalization for cADRs was highest for
Cephalosporins: 4.92 per 1000 prescriptions (95% CI, 4.86 to 4.99)
Sulfonamide antibiotics: 3.22 per 1000 prescriptions (95% CI, 3.15 to 3.28)
Among those who were hospitalized for cADRs
Median length of stay: 6 days (IQR, 3 to 13)
Transferred to critical care: 9.6%
Died in the hospital: 5.3%
CONCLUSION:
Several classes of common oral antibiotics are associated with serious cADRs, especially sulfonamides and cephalosporins
The authors state
The absolute risk of antibiotic-associated serious cADRs appeared relatively low, with 2 cADR-related hospital visits for every 1000 antibiotic prescriptions dispensed to older adults
The findings highlight the risk of serious cADRs following commonly prescribed antibiotics and underscore the importance of judicious prescribing, with preferential use of those associated with a lower risk when clinically appropriate
In conclusion, this meta-analysis revealed a significant reduction in the size of ovarian endometriomas with dienogest, OCPs, GnRH agonists, norethindrone acetate, norethindrone acetate with aromatase inhibitor, and danazol use. Adequate high-quality evidence is lacking for other interventions, as are optimal duration of therapy and long-term data
Does Vaginal vs Cesarean Delivery Reduce Maternal Morbidity for Patients with Cardiomyopathies?
BACKGROUND AND PURPOSE:
Cardiomyopathies are a risk factor for pregnancy complications, but the optimal mode of delivery for these patients is not well established
Meng et al. (Journal of the American College of Cardiology HF, 2023) examined the association of delivery mode with severe maternal morbidity events during delivery hospitalization and readmissions among patients with cardiomyopathies
METHODS:
Retrospective cohort study
Population
Pregnant patients with cardiomyopathy
Exposures
Vaginal delivery
Cesarean delivery
Primary outcome
Pregnancy outcomes in the intention-to-treat population (planned cesarean)
Nontransfusion severe maternal morbidity during the delivery hospitalization | Blood transfusion | Readmission
Secondary outcomes
Pregnancy outcomes in the as-treated population (cesarean delivery)
RESULTS:
2921 deliveries
In the intention-to-treat population, there was no difference in any of the primary outcomes between the vaginal delivery and cesarean
Nontransfusion morbidity: Adjusted odds ratio (aOR) 1.17 (95% CI, 0.91 to 1.51)
Blood transfusion: aOR 1.27 (95% CI, 0.81 to 1.98)
Readmission: aOR 1.03 (95% CI, 0.73 to 1.44)
In the as-treated population, cesarean delivery was associated with a higher incidence of
Nontransfusion morbidity: aOR 2.44 (95% CI, 1.85 to 3.22)
Blood transfusion: aOR 2.26 (95% CI, 1.34 to 3.81)
CONCLUSION:
For pregnant patients with cardiomyopathies, trial of labor does not increase the incidence of maternal morbidities compared to a planned cesarean delivery
RCT Results: Is Weight Loss Maintained After Discontinuing Use of Tirzepatide?
BACKGROUND AND PURPOSE:
Previous trials have demonstrated the efficacy of tirzepatide, a once-weekly injectable GLP-1 receptor agonist, for the treatment of obesity and overweight with or without diabetes
Over 72 weeks, mean reduction of body weight was up to approximately 20%
Aronne et al. (JAMA, 2023) assess the effect of tirzepatide withdrawal on the maintenance of weight reduction
METHODS:
Phase 3, randomized withdrawal clinical trial
SURMOUNT-4 trial
Participants
Adults with a BMI ≥30 or
≥ 27 and a weight-related complication
Exclusion: Diabetes
Interventions
36 weeks once-weekly subcutaneous maximum tolerated dose (10 or 15 mg) of tirzepatide, followed by
Continuation for 52 weeks
Switch to placebo
All patients received diet and exercise counseling
Primary outcome
Mean percent change in weight from week 36 to week 88
Secondary outcomes
Proportion of participants at week 88 who maintained at least 80% of the weight loss during lead-in
RESULTS:
670 participants
Mean age: 48 years | Women: 71% | Mean weight: 107.3 kg
Mean weight reduction in 36-week lead-in: 20.9%
From week 36 to week 88, there was a significant difference in mean percent weight change among the continuation and placebo cohorts
Continuation: –5.5% | Placebo: 14.0%
Difference –19.4% (95% CI, –21.2 to –17.7) | P<0.001
A greater proportion of patients in the continuation cohort maintained at least 80% of the lead-in weight loss, compared to the placebo cohort
Continuation: 89.5% | Placebo: 16.6% | P<0.001
Overall mean weight reduction from week 0 to 88
Continuation: 25.3%
Placebo: 9.9%
Most common adverse events
Mild to moderate gastrointestinal events
CONCLUSION:
Participants with overweight and obesity who received placebo after 36 weeks of tirzepatide experienced substantial weight regain
Participants who continued tirzepatide maintained the initial weight loss, and even furthered improved their weight
The authors state
At least 5 trials (including the present study) across various classes of medications, including potent antiobesity medications such as semaglutide, have demonstrated that weight is substantially regained after cessation of pharmacotherapy
The consistency of these data across therapeutic classes spanning more than 2 decades suggests that obesity is a chronic metabolic condition similar to type 2 diabetes and hypertension requiring long-term therapy in most patients
What Proportion of Fetal Deaths Are Linked to Placental SARS-CoV-2 Infection?
BACKGROUND AND PURPOSE:
In-utero fetal death (IUFD) may occur when SARS-CoV-2 is vertically transmitted to the placenta, leading to placental insufficiency
Nkobetchou et al. (Ultrasound in Obstetrics & Gynecology, 2023) quantified the extent to which fetoplacental infection with SARS-CoV-2 is a cause of fetal death
METHODS:
Multicenter retrospective cohort study
Paris, France
Between January 2020 and January 2022
Population
Fetal deaths that underwent postmortem examination
Exposures
IUFD with a placental or undetermined cause
Termination of pregnancy (TOP) in the context of severe intrauterine growth restriction (IUGR)
Study design
Cases with fetal malformation or cytogenetic abnormality were excluded to avoid bias
Placentas were sent to a single virology unit for blinded RT-PCR testing
Primary outcome
Proportion of positive placental SARS-CoV-2 tests
RESULTS:
147,722 deliveries | 462 postmortem examinations for IUFD and TOP for severe IUGR
Positive SARS-CoV-2 tests in the placenta: 2.8% (13 of 462 postmortems)
All positive cases had histological lesions consistent with placental dysfunction
There was an association between SARS-CoV-2 placentitis and the presence of chronic intervillositis and massive fibrin deposits in the placenta
Diagnosis of placental SARS-CoV-2 infection when both lesion types were present
Specificity: 0.99 (95% CI, 0.98 to 1.00)
Negative predictive value: 0.96 (95% CI, 0.94 to 0.98)
Diagnosis of placental SARS-CoV-2 infection when both lesion types were present
CONCLUSION:
Among fetal death cases that were of placental or undetermined origin, 2.8% cooccurred with placental SARS-CoV-2 infection
Cases with a positive test for SARS-CoV-2 were associated with a specific pattern of histological involvement
The authors state
This study confirms that maternal SARS-CoV-2 infection is the cause of IUFD and severe IUGR via virus-mediated placental damage
In view of our findings, systematic placental testing for SARS-CoV-2 seems justified in cases of IUFD or TOP for severe IUGR with normal genetics, especially in the presence of a specific histological pattern documented herein
RCT: Is Faster Insulin Aspart Safe for Use in Pregnancy and Post-Pregnancy?
BACKGROUND AND PURPOSE:
While faster-acting insulin aspart (faster aspart) is generally regarded as safe for pregnant and breastfeeding individuals, it has not been explicitly evaluated in this population
Nørgaard et al. (The Lancet Diabetes and Endocrinology, 2023) evaluated the effect of faster aspart vs insulin aspart among pregnant women with type 1 or type 2 diabetes
METHODS:
Open-label, single-center, superiority trial
Conducted in Copenhagen, Denmark
Participants
Individuals aged 18 years or older with type 1 or type 2 diabetes from 8w0d to 13w6d
Interventions
Faster aspart
Insulin aspart
Study design
Stratification by diabetes type and insulin treatment modality (multiple daily injections or insulin pump)
Follow-up through 3 months post-delivery
Primary outcome
Infant birthweight standard deviation score (also known as z-score)
RCT: Hysteroscopic Morcellation vs Suction Curettage for Retained Products of Conception
BACKGROUND AND PURPOSE:
Wagenaar et al. (Fertility and Sterility, 2023) compared the risk of intrauterine adhesions (IUAs) and efficacy of hysteroscopic morcellation vs ultrasound-guided electric vacuum aspiration for retained products of conception (RPOC)
METHODS:
Nonblinded randomized controlled trial
Participants
RPOC on ultrasound
Ranging from 1 to 4 cm
Following miscarriage, termination of pregnancy, or delivery
Interventions
Hysteroscopic morcellation (HM)
Electric vacuum aspiration
Study design
Morcellation:
Performed with the TruClear System
Removal ≥8 weeks after the end of the pregnancy
Electric vacuum aspiration
Performed using an 8- or 10-mm flexible plastic Karman cannula under ultrasound guidance
Women allocated to this intervention group underwent the procedure as soon as possible
Primary outcome
IUAs, assessed postoperatively with a second-look hysteroscopy
Do the New Guidelines for Diagnosing Nonprogressing Labor Actually Reduce Cesarean Deliveries?
BACKGROUND AND PURPOSE:
Wood et al. (AJOG, 2023) assessed whether adoption of new guidelines for diagnosing nonprogressing labor reduced cesarean delivery rates
METHODS:
Cluster randomized controlled trial
26 Canadian hospitals
Province of Alberta
REDucing the utilization of CEsarean delivery for dystocia (REDUCED trial)
Participants
Nulliparous
Vertex presentation
In labor at term
Intervention
Intervention sites: 2014 guidelines for nonprogressing labor
Control sites: Operated under usual care
Old guidelines (2012)
First stage arrest: ≥6 cm dilation with rupture and no cervical change for ≥4 hours with adequate contractions or ≥6 hours with inadequate contractions
Second stage arrest: No progress for ≥4 hours in nulliparous with epidural or ≥3 hours in nulliparous without epidural
New guidelines (2014)
First stage: Prolonged latent stage (e.g., ≥20 hours in nulliparous) should not be considered an indication for cesarean | Slow but progressive labor should not be indication for cesarean
Second stage: Specific maximum time at which point women should undergo operative delivery has not been established | Allow at least 3 hours pushing in nulliparous | Longer times may be indicated on individualized basis
Study design
Data from all sites from the baseline (2015–2017) and follow-up (2017–2020) periods
Intention to treat approach
Cesarean delivery rates assessed using repeated measures mixed effects logistic regression applied to individual births
Primary outcome
Rate of cesarean delivery
Secondary outcomes
Spontaneous vaginal birth
Maternal and neonatal safety
RESULTS:
Deliveries at intervention sites: 45,193 | Deliveries at control sites: 43,725
There was no evidence of a decrease in the rate of cesarean delivery when the new 2014 guidelines were implemented
Baseline-adjusted odds ratio 0.94 (95% CI, 0.85 to 1.05) | P=0.259
The rate of spontaneous vaginal delivery increased slightly
Baseline-adjusted odds ratio 1.10 (95% CI, 1.01 to 1.18) | P=0.024
There were no differences in adverse maternal or neonatal outcomes
CONCLUSION:
Randomized implementation of 2014 guidelines for diagnosing nonprogressing labor did not reduce cesarean deliveries
Hospitals that implemented the intervention did experience increased spontaneous vaginal deliveries
Implementation of the guidelines did not have adverse effects
The authors state
Furthermore, this trial was conducted in a setting where midpelvic forceps deliveries are performed more often than cesarean deliveries. Therefore, if the intervention had been tested in a setting where this is rarely done, the cesarean delivery rate may have been more substantially reduced
Secondary Analysis of the ANODE Trial: Does the Benefit of Antibiotics Following Operative Birth Depend on Presence of Episiotomy?
BACKGROUND AND PURPOSE:
The ANODE trial (see ‘Related ObG Topics’ below) showed that prophylactic antibiotics reduced infection burden following operative delivery
However, episiotomy rates were high and infections remained high even in the treatment group
Humphreys et al. (AJOG, 2022) sought to determine whether the effectiveness of the prophylactic antibiotic at reducing infection was independent of perineal trauma
METHODS:
Secondary analysis of ANODE RCT
Population
Forceps or vacuum assisted birth at ≥36 weeks
Exclusion: Missing data or withdrew consent
Primary interventions
IV prophylactic amoxicillin and clavulanic acid
Placebo
Study design
Received intervention/placebo as soon as possible immediately after delivery to ≤6 hours
Primary outcome
Consistency of the prophylactic antibiotics in preventing infection across the exposure subgroups
RESULTS:
3225 women
Episiotomy alone: 66.5%
Episiotomy and a tear: 22.5%
Tear alone: 8.6%
Neither episiotomy nor tear: 2.4%
Among women who experienced perineal trauma, amoxicillin and clavulanic acid administration were protective against infection in all subgroups
The following were associated with higher risk of infection
Episiotomy: Adjusted risk ratio (aRR) 2.94 (95% CI, 1.62 to 5.31)
This study has found no evidence to suggest that prophylactic amoxicillin and clavulanic acid administration is less protective against confirmed or suspected infection after OVB with perineal trauma in the absence of episiotomy, which provides reassurance of the benefit of prophylactic antibiotic in settings where the episiotomy rate is lower
Importantly for clinical practice, the burden of infection may be further reduced by timely administration of the antibiotic to all women irrespective of the state of their perineum
Hysteroscopy can be performed either in the operating room or the office. When planning a hysteroscopic procedure, the joint ACOG/AAGL recommendations include the following
Preoperative consultation
Discuss risks/ benefits/ alternatives
Review medical history
Exclude pregnancy if appropriate
If cervical stenosis is present
Consider misoprostol (off label) 200 to 400 mcg buccal/ sublingual/ intravaginal the night before surgery
Optimize visualization
Perform during follicular phase of cycle, after menses | Secretory phase may mimic polyps: Irregular menses may be scheduled at any time
Actively bleeding “may not undergo the procedure” due to decreased visibility
Pretreatment with progestins or combined OCP may further optimize visualization by thinning the endometrial lining
Antibiotic prophylaxis not recommended
Pain management
Multiple pharmacologic approaches described, but evidence insufficient to recommend any particular analgesic regimen | No regimen has been shown to be superior to placebo
Note: Mannitol 5% is iso-osmolar and while may cause hyponatremia, should not decrease serum osmolality
Electrolyte-containing fluids
Normal saline | Lactated Ringer’s solution
Use for
Diagnostic cases
Laser | Bipolar | Mechanical energy
Less risk of hyponatremia/ decreased osmolality
SYNOPSIS
Polyps, synechiae, Mullerian abnormalities, leiomyomata and retained foreign bodies can often be diagnosed and treated successfully with hysteroscopy. Visualization of the endometrial cavity allows biopsy of abnormal areas and can optimize the diagnosis of hyperplasia or malignancy
KEY POINTS:
Complications
Vasovagal
Signs and symptoms
Hypotention | Bradycardia
Sweating | Pallor | Loss of conciousness | Nausea and vomiting
Management
Assess: Vitals | Airway, Breathing, Circulation
Place patient in Trendelenberg or raise legs
If bradycardia does not resolve
Atropine: Single dose 0.5 mg IV q3 to 5 minutes (total dose 3 mg)
Fluid Overload and Hyponatremia
Prevention
Strictly monitor both IV hydration and hysteroscopic fluid deficit
Electrolyte poor fluids maximal deficit: 1000 mL (in healthy individuals)
Consider stopping procedure at 750 mL deficit
Electrolyte-containing fluids maximal deficit: 2500 mL (in healthy individuals)
Consider stopping procedure at 2000 mL deficit
Consider lower thresholds for elderly, cardiovascular or renal comorbidity or when laboratory services/ acute care options are limited
Management
Hypertonic saline solution and diuretics (e.g., furosemide)
Increase serum sodium levels by 1 to 2 mEq/L/h
Caution: Do not increase by more than 12 mEq/L in the first 24 hours
Transfer to an urgent care facility and further consultation may be required
Hemorrhage
Management
Apply electrosurgical coagulation if bleeding sites identified
Inject vasopressin into the cervix
Use Foley catheter balloon tamponade or manual uterine compression
Surgical approach as a last resort includes
Laparoscopic suturing of perforation
Hysterectomy
Uterine artery embolization
Uterine Perforation
Prevention
Perform careful pelvic exam prior to hysteroscopy
Use ultrasound guidance as needed
If flexible hysteroscope available, insertion may be performed prior to using dilators
Management
Midline perforation is seldom morbid unless laser or electrosurgery is used
Lateral perforations carry risk for retroperitoneal hematomas
Discontinue hysteroscopy if perforation occurs
Consider laparoscopy to
Identify any bowel/ bladder injury
Check for hematomas
Air/CO2 Embolization
Prevention
Purge and flush air from tubing prior to procedure and whenever bags are changed | Avoid repetitive instrument insertions | Limit intrauterine pressure
ACOG has published two committee opinions on carrier screening. Committee Opinion 691 reviews the recommendations based on disorders. Committee Opinion 690 addresses the issues related to use of screening strategies such as expanded gene panel testing.
Key Highlights
Spinal Muscular Atrophy (SMA) has joined cystic fibrosis (CF) as a recommendation for all women who are pregnant or considering pregnancy
Hemoglobinopathies
Test all patients for CBC and RBC indices as part of antepartum care (ideally preconception)
Add Hgb electrophoresis if
Increased risk based on ethnicity: African, Middle Eastern, Southeast Asian, West Indian and Mediterranean ancestry
MCV is less than 80 fL with normal iron studies
Ashkenazi Jewish Testing (central and Eastern Europe descent)
Additional tests to ‘consider’ has been expanded to the following
Usher syndrome, Familial hyperinsulinism, Joubert and Maple syrup urine disease in addition to Bloom/Gaucher/Fanconi anemia/ML4/Neimann-Pick disease
Tay Sachs Disease
In addition to Ashkenazi Jews, offer if either partner is French-Canadian descent or Cajun
Screening can be performed using DNA-based testing (mutation analysis) or hexosaminidase enzyme in serum or leuckocytes (leukocyte only with oral contraceptives)
Enzyme testing picks up approximately 98% of carriers regardless of ethnicity
Mutation analysis is highly effective in at risk populations – detection rate is limited in other populations
Committee Opinion 690 reviews expanded carrier screening, including a discussion on counseling and what disorders should be included | Important summary statements include the following
Ethnic-specific, panethnic, and expanded carrier screening are acceptable strategies for prepregnancy and prenatal carrier screening. Each obstetrician–gynecologist or other health care provider or practice should establish a standard approach that is consistently offered to and discussed with each patient, ideally before pregnancy. After counseling, a patient may decline any or all carrier screening.
Expanded carrier screening does not replace previous risk-based screening recommendations. If obstetrician–gynecologists or other health care providers do not offer expanded carrier screening in their practice, screening recommendations for individual disorders should follow guidelines for carrier screening as outlined in Committee Opinion No. 691, Carrier Screening for Genetic Conditions.
Note: ACMG has published a document on preconception and prenatal carrier screening that includes a tiered approach to the selection of disorders | For the summary and links see ‘Related ObG Topics’ below)
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Disclosure of Unlabeled Use
This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. The planners of this activity do not recommend the use of any agent outside of the labeled indications.
The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of the planners. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.
Disclaimer
Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information
presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications and/or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.
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