Use of alternative antibiotics during C-section increase the odds of wound infection

Use of alternative antibiotics other than the standard recommendation of the first-generation cephalosporin is associated with increased risk of infection and other adverse events, according to a new analysis of more than 6500 cesarean section deliveries. Cephazolin in the drug of choice for surgical prophylaxis in C-section deliveries.

"Use of both standard alternative and inappropriate alternative antibiotics was associated with higher odds of surgical site infections compared with the use of cefazolin for prophylaxis at the time of cesarean delivery," conclude the authors in the study published September 7 in Journal Obstetrics & Gynecology.

The American College of Obstetricians and Gynecologists (ACOG) recommend an infusion of intravenous 1 g cefazolin within 60 min before skin incision. For women with (BMI >30 kg/m 2 or weight > 100 kg, a dose of 2 g cefazolin intravenous infusion is recommended.

In women who are allergic to cephalosporin ACOG recommends alternative antibiotics, such as clindamycin combined with an aminoglycoside.

In this retrospective cohort study conducted over a period of 5 years (2012 – 2017), Tetsuya Kawakita, MD, Department of Obstetrics and Gynecology, MedStar Washington Hospital Center, Washington, DC, and colleagues analyzed data from 6584 women who had cesarean delivery in their center.

Majority of women, 6163(93.6%) received standard cefazolin, 274 (4.2%) received the standard alternative, while 147 (2.2%) received inappropriate alternatives— mostly clindamycin or gentamycin.

Propensity score adjusted logistic regression showed that use of alternative antibiotic was not associated with increased risk of the composite primary outcome namely endometritis, cellulitis, deep-wound infection, abdominopelvic abscess, and sepsis. But a subgroup analysis revealed that use of alternative antibiotic increased chances of cellulitis by 93% as compared to use of cephalosporins (adjusted odds ratio [OR], 1.93; 95% CI, 1.03 - 3.31).

Patient receiving alternative antibiotic faced nearly twice the risk of visiting the ER for wound complication (adjusted OR, 2.34; 95% CI, 1.19 - 4.18) compared with cefazolin.

Similarly, use of inappropriate antibiotics increased the odds of primary outcome nearly 4 times as compared to cephazolin (adjusted OR, 4.13; 95% CI, 2.59 - 6.36), while odds of endometritis (adjusted OR, 6.68; 95% CI, 3.69 - 11.44) and cellulitis (adjusted OR, 3.23; 95% CI, 1.63 - 5.81) also increased drastically.

The authors speculated that the difference in sensitivity of skin bacterial flora to the alternative antibiotics might be responsible for increased odds of having cellulitis after the C-section. More studies are warranted on alternate antibiotics other than those recommended by ACOG.

Besides, the authors also stressed that physicians should validate the patients claim of allergy to beta-lactam antibiotics and should not only rely on history given by the patients. They found that only 10-20% of patients documented true allergy on skin testing.

If patients gave a history of nonsignificant beta-lactam allergies, use of cefazolin in such patients might lower the risk of adverse event during cesarean delivery.

Abstract

More on prevention of sepsis during cesarean deliveries:

What is best for Cesarean Antisepsis? Chlorhexidine-Alcohol versus Povidone-Iodine

News from ACOG 2017: Changing gloves before abdominal closure brings down the rate of wound infection by almost 50% in Cesarean Section

Maternal clinical risk factors for the increased rate of post-cesarean infection identified

Use of Monocryl suture minimizes wound complications in cesarean sections - News from SMFM 2017, Las Vegas

Vaginal cleaning before cesarean delivery significantly reduces infection: A Systematic Review and Meta-analysis

Vaginal cleansing with antiseptic solution before cesarean section brings down postoperative infection: Cochrane review

A simple and inexpensive intervention of vaginal cleaning with the chlorhexidine-based or iodine-based solution immediately before cesarean section probably reduces the risk of endometritis after the procedure. The benefit could be more for women who underwent cesarean section while in labor or after rupture of membranes reports the results of a Cochrane review published 17 July 2018.

The current review is the fifth update on vaginal preparation before cesarean section and risk of subsequent infection by Cochrane; the first review was published in 2010 and subsequently updated in 2012, and twice in 2014.

Cesarean section is the most commonly performed operation in obstetrics, with 1 in 3 babies being born by cesarean section. Nearly 25% of women have endometritis and 10% of women develop skin infection after C-section.

Pre-op or intra-op antibiotic prophylaxis has not been able to bring down the rate considerably.

The Cochrane researchers searched the Cochrane Pregnancy and Childbirth’s Trials Register, the WHO International Clinical Trials Registry Platform (ICTRP) (10 July 2017), ClinicalTrials.gov, and reference lists of retrieved studies.

The review included 11 trials with a total of 3403 women in whom vaginal preparation was done immediately before the start of the cesarean section. Most of the trials used Povidone-iodine (n=8), while the rest used chlorhexidine (n=2) and benzalkonium chloride (n=1).

The control group included women with no vaginal antisepsis preparation (eight trials) or those in whom saline vaginal preparation (three trials) was used.

Vaginal preparation with the antiseptic solution immediately before cesarean delivery probably reduced the risk of endometritis by 64% (average risk ratio (RR) 0.36, 95% confidence interval (CI) 0.20 to 0.63).

It was not possible to separately analyze the risk reduction in a subgroup of women who were in labor or in women whose membranes had ruptured when antiseptics were used. 

Risk of postoperative fever or surgical wound complications may also be brought down by the use of vaginal antisepsis, but the confidence interval around the effects for both outcomes was very wide consistent with insufficient data.

Composite outcome of wound complication or endometritis was reduced by 54% in two trials consisting of 499 women (RR 0.46, 95% CI 0.26 to 0.82).

No adverse effects were reported with either the povidone-iodine or chlorhexidine vaginal cleansing.

The quality of evidence using GRADE was moderate for all reported outcomes. The authors downgraded the outcome for post-cesarean endometritis and composite of wound complications or endometritis because of bias in the involved study and broader CI.

The recommend that healthcare providers may continue using vaginal antisepsis preparation by either using povidone-iodine or chlorhexidine before performing a cesarean delivery.

Abstract

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Prophylactic negative pressure wound therapy may help cut down surgical wound infections after cesarean

Prophylactic negative pressure wound therapy (NPWT) at cesarean delivery may reduce the surgical site infections (SSI) and overall wound complications says the results of a systematic review and meta-analysis published ahead of print in American journal of obstetrics and gynecology.

Morbidly obese women have a very high rate of SSIs and readmission to hospitals.

The researchers conducted a literature review and included RCTs and observational studies comparing surgical outcome between prophylactic negative pressure wound closure and standard cesarean wound closure.  

The investigators were mainly looking at difference in SSI because of NPWT besides other minor outcomes like composite wound complications, wound gaping, hematoma, endometritis and readmission to the hospital.

Six RCTs and three cohort study met the inclusion criteria. It was seen that women with NPWT faced a 55% lower risk of SSI as compared to women with standard dressing (pooled RR 0.45; 95% CI 0.31- 0.66). The Number Need to Treat (NNT) was 17.

Women with NPWT also had a 22 lower risk of composite wound complications, while the other minor outcomes were comparable in both the groups.

The authors concluded that although the studies were heterogenous, use of NPWT decreases the SSIs after  cesarean, larger clinical trials are awaited to fully understand the impact of the intervention.

Abstract

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Vaginal cleaning before cesarean delivery significantly reduces infection: A Systematic Review and Meta-analysis.

A simple and inexpensive intervention of vaginal cleaning with an antiseptic solution before cesarean delivery brings down the rate of endometritis note the results of a Systematic Review and Meta-analysis published August 4 in Journal of Obstetrics and Gynecology.

The effect was significantly more in patients in labor or with ruptured membranes at the time of the procedure.

Claudia Caissutti, MD, from the Department of Experimental Clinical and Medical Science, Clinic of Obstetrics and Gynecology, University of Udine, Italy, and colleagues searched MEDLINE, Ovid, EMBASE, Scopus, Clinicaltrials.gov, and Cochrane Library from their inception to January 2017.

They included randomized trials comparing vaginal cleaning with any antiseptic against placebo or no cleaning at all. The final data for review came from 16 RCTs, with a total of 4,837 women in whom vaginal preparation was done immediately before the start of cesarean section.

Most of the trials used povidone–iodine (n = 11) as the cleaning agent, while rest used chlorhexidine diacetate solution n = 3) , metronidazole vaginal gel prep ( n =1), and Cetrimide ( n =1) .

The observed incidence of endometritis in women who received preoperative vaginal cleansing was nearly 50% less as compared to women with placebo or no cleaning (4.5% vs 8.7%; relative risk [RR], 0.52; 95% confidence interval [CI], 0.37 - 0.72). These group also had significantly lower incidence of postoperative fever (9.4% compared with 14.9%; RR, 0.65).

No significant difference was observed in postoperative wound infection among the groups.

In a separate planned subgroup analysis, the observed difference in rates of endometritis was only seen in women who were in active labor and for patients with rupture of membranes. Four trials stratified the data according to women were in labor or not and three trials looked into women with and without ruptured membranes.

When the data was stratified according to type of cleaning agent and prophylactic antibiotics, the results were in according to the overall analysis.

Women who received prophylactic antibiotics had a 67% decrease in endometritis incidence. The authors opined, "Surgical prophylaxis with intravenous antibiotics before cesarean delivery has been clearly demonstrated as beneficial in reducing postoperative infection morbidity, Thus, it is the standard of care and these findings could translate to current practice."

The results of study have confirmed the findings of earlier Cochrane database systematic review published in 2013.

Data is needed to assess the effect of vaginal cleaning in women not in labor and without ruptured membranes.

The authors concluded that, “Vaginal cleansing immediately before cesarean delivery in women in labor and in women with ruptured membranes reduces the risk of postoperative endometritis. We recommend preoperative vaginal preparation before cesarean delivery in these women with sponge stick preparation of povidone-iodine 10% for at least 30 seconds.”

PCOS is often underdiagnosed as the common cause of Abnormal Uterine Bleeding in Adolescents.

Image courtesy: University of Utah.

 Abnormal uterine bleeding(AUB) is very frequent in adolescents and generally lasts for 4-5 years after menarche. It is an important cause of visit to emergency room or healthcare provider in pediatric patients. Although DUB due to immaturity of hypothalamic pituitary ovarian (HPO) axis is a common cause of AUB in healthy adolescent, it is also important to rule out other pathological causes.

PCOS as a cause of AUB in adolescent’s patients is often underdiagnosed and poses a diagnostic dilemma as normal pubertal changes like acne, menstrual irregularities and hyperinsulinemia can mimic several features of PCOS.

Prompt diagnosis and treatment of PCOS is very important because of future reproductive and metabolic repercussions.[1] Evidence suggests that adolescents diagnosed with PCOS have elevated risk of Metabolic Syndrome (MetS) and premature cardiovascular dysfunction and cardiovascular disease.[2]

Adolescents with AUB are mostly managed as outpatients but some require hospitalization because of hemodynamic instability. A recent paper published in Journal of Pediatricand Adolescent Gynecology evaluated the most common etiology for AUB in hospital admitted adolescent patients with severe anemia.[3]

This retrospective study was conducted by Dr. Sofya Maslyanskaya, Assistant Professor of Pediatrics, Albert Einstein College of Medicine, Bronx, New York and her colleague at Children's Hospital at Montefiore in New York City.

The researchers identified 125 females aged 8 to 20 years admitted to the hospital for anemia with AUB from January 2000 to December 2014.

As per hospital protocols, all the subjects underwent hormonal testing for PCOS and other endocrinal disorders. Hence the data could be accessed and reviewed by the researchers for laboratory test results, treatment and final diagnosis.

The demographics of the study subjects were: mean age at the time of admission was 16 years, mean Hb 7gm/dl, nearly half were obese and 41% sexually active.

PCOS was diagnosed as the leading cause (33%) for hospital admissions for severe bleeding, followed by HPO axis immaturity in 31% of cases. Endometritis was responsible for 13% of admissions while bleeding disorder accounted for 10%.

Nearly three-fourth of teenagers diagnosed with PCOS were obese while subjects with HPO axis immaturity have the lowest Hb level as compared to other etiologies.

The lead author stressed the need for ruling out PCOS as the cause of AUB before any form of treatment is started, especially in adolescent girls admitted for anemia with AUB. Once hormonal treatment is started the diagnosis becomes more difficult.

The study results cannot be generalized to patients with less severe DUB. Also, the participants were mostly from Asian and Latino communities, so the results may not apply to other demographics.

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[1] http://contemporaryobgyn.modernmedicine.com/contemporary-obgyn/content/tags/adolescent-gynecology/pcos-adolescents-beyond-reproductive-implicati

[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3703718/

[3] http://www.jpagonline.org/article/S1083-3188(16)30284-4/abstract

Prophylactic Use of Azithromycin brings down Postcesarean Infections.

Clinical pearls:

• Among women undergoing non-elective cesarean section, addition of azithromycin to the standard protocol of prophylactic antibiotic reduces the risk of postoperative infection significantly. (P<0.001).
• A single dose of 500 mg used Intravenously before the skin incision.

According to data by CDC, out of nearly 4 million children born in USA, 1,284,551 are delivered by cesarean sections. The Cesarean section rate in US is 32.2%.[1] Women who undergo cesarean delivery are 5-10 times more at risk for puerperal infection as compared to women undergoing a natural birth. [2]Puerperal infection is responsible for 10% of pregnancy-related mortality. 

Postoperative infectious morbidity also encompasses other causes like mastitis, septic pelvic thrombophlebitis, drug fever, urinary tract infection/pyelonephritis and pneumonia but two major contributors to maternal morbidity and mortality are endometritis (incidence without prophylaxis, 4 to 18%) and of surgical-site infections (incidence without prophylaxis, 7 to 10%.).

To prevent surgical site infections ACOG recommends the use of a single dose of a narrow spectrum first-generation cephalosporin (cefazolin), or a single-dose combination of clindamycin with an aminoglycoside for those with a significant penicillin allergy, as prophylaxis for cesarean delivery.[3]

A large randomized trial published in the September 29 issue of the New England Journal of Medicine presents the result of adding Azithromycin (a macrolide antibiotic) to standard prophylaxis for cesarean deliveries at 14 U.S. hospitals.[4]

The study was also presented in part at the 36th annual meeting of the Society for Maternal–Fetal Medicine, Atlanta, February 1–6, 2016.

The study included 2013 women who were at least 24+ weeks into pregnancy, with singleton fetus, undergoing an emergency section in labor with or without rupture of membranes. Women with elective or planned cesarean sections were excluded from the study. The study cohort was divided into 2 groups. The study group received single 500-mg dose of azithromycin intravenously before the cesarean incision, in addition to the intravenous dose of cefazolin that is standardized protocol followed at each center.

The control group received cefazolin plus placebo.

Data Analysis showed that the occurrence of primary composite outcome like surgical site infection, endometritis (measured 6 weeks postpartum) and other infection were significantly lower in the group receiving Azithromycin (6.1% vs. 12.0%, P<0.001).

Secondary outcome like readmissions, emergency visit to hospital and need for antibiotics postpartum were also less in the study group. 

Neonatal outcomes were similar in both the groups. "Pharmacologic data indicating that azithromycin only minimally crosses the placenta into the fetal circulation suggest limited exposure for the infant," write Dr Weinstein and Dr Boyer in an accompanying editorial.

The study results also showed that 17 women need to be treated to prevent the occurrence of primary study outcome, while the number for preventing one case of endometritis and wound infections is 43 and 24 respectively.

The number of eligible women who would need to be treated to prevent one study outcome was 17 for the primary outcome, 43 for endometritis, and 24 for wound infections. 

The editorial authors hypothesized that Azithromycin is effective against some of vaginal microbiota. Earlier studies have shown that genital or placental colonization with Ureaplasma urealyticum increases the risks of endometritis/ wound site infection.

Azithromycin is also concentrated and retained for many days in myometrium and adipose tissue, hence a single dose preoperatively works well for this surgery.

So, does the study implicate the routine use of Azithromycin as a preoperative prophylaxis in cesarean section?  The editorial authors opine that it is too early to make any recommendation. "Time will tell whether such findings result in changes in routine antibiotic prophylaxis before cesarean deliveries," write Dr Weinstein and Dr Boyer. 

However, on the basis of the results, the addition of azithromycin "would reduce a number of infectious complications for some women without established infections who are undergoing nonelective cesarean section."

The emergence of antibiotic resistant organism after long use also has to be kept in mind, but a single I/V dose is unlikely to do so.

The study findings show that by adding prophylactic azithromycin to the routine protocol for cesarean delivery extends   the spectrum of coverage and decreases the chances of puerperal infection without compromising maternal or neonatal safety.    

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[1] http://www.cdc.gov/nchs/fastats/delivery.htm

[2] Gibbs RS. Clinical risk factors for puerperal infection. Obstet Gynecol 1980;55:5 Suppl:178S-184S

[3] American College of Obstetricians and Gynecologists (ACOG), authors Use of prophylactic antibiotics in labor and delivery. [Accessed May 13, 2012]. Practice Bulletin No. 120, June 2011. US Department of Health & Human Services Web site.

[4] http://www.nejm.org/doi/full/10.1056/NEJMoa1602044

Preincisional Azithromycin cuts postcesarean maternal infection by half.

The CesareanSection Optimal Antibiotic Prophylaxis (C/SOAP) study is a large pragmatic multi-center randomized clinical trial designed to evaluate the comparative effectiveness and safety of azithromycin-based extended-spectrum antibiotic prophylaxis (azithromycin plus standard narrow-spectrum cephalosporin) relative to standard single-agent cephalosporin (preferably prior to surgical incision) to prevent post-cesarean infection.

Paired with standard prophylactic antibiotics, broad-spectrum intravenous azithromycin was highly effective, with a number needed to treat of 17 to prevent one postsurgical infection, and 43 to prevent one case of endometritis, Dr. Alan Tita reported at the 36^th annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

“We also saw fewer maternal adverse events, and the protocol was safe for the newborn,” said Dr. Tita, who is a professor of obstetrics and gynecology at the University of Alabama, Birmingham.

This trial enrolled 2,013 women at 14 sites, who had singleton pregnancy of at-least 24 weeks, not scheduled for elective LSCS and underwent surgery after being in active labor for at-least 4 hours or 4 hours after rupture of membranes.

All women received standard preoperative antibiotic prophylaxis with either cefazolin or clindamycin. The women were than randomized to receiving either preincisional intravenous azithromycin 500 mg or a placebo.

As the study was multicentric, skin preparation was done according to standard protocols at each center.

The primary outcome measures were composite of endometritis and/or wound infection and/or other post-cesarean infections (occurring within 6 weeks of delivery) and the secondary outcomes were individual post-cesarean infections: Endometritis, wound infection (including necrotizing fascitis), other infections including abscess, septic thrombosis, pneumonia, pyelonephritis and breast infection.

The neonatal outcome was a composite of death; primary or suspected sepsis; and serious neonatal morbidities, including respiratory distress syndrome, necrotizing enterocolitis, periventricular leukomalacia, intraventricular hemorrhage of grade 3 or higher, and bronchopulmonary dysplasia.

It was seen that the rate of primary composite outcome was reduced by half in the study group (6% vs. 12%; relative risk, 0.49). Wound infection decreased by 65% (2.4% vs. 6.6%; RR, 0.35). 

Azithromycin significantly improved the maternal outcome like fever, readmission, revisit also.

The use of azithromycin was safe for neonates too and the researchers did not see much difference for the composite neonatal safety outcome in study vs the placebo group.   The rates for treatment and placebo groups were not different for suspected or confirmed sepsis (11.8% vs. 12.5%), serious neonatal morbidities (4.4% vs. 3.4%), or NICU admission (16.8% vs. 17%).

No maternal deaths were reported, 11 patients had allergic reaction, while five women admitted to intensive care, and five other had suspected cardiac events.

Concerns regarding the alteration of the fetal microbiome by brief systemic exposure to azithromycin were raised at the conference.

“We have collected additional information and specimens and we will be looking at these to try and answer this. We also hope to get funding to do a long-term evaluation of these kids. I will say that we collected adverse event data on them for 3 months and we did not see anything concerning, but I agree more needs to be done,” he said. “Having said that, azithromycin is something we already use quite a lot in obstetrics, and overall it has been shown to be safe for the newborn.”

Dr. Tita reported having no financial disclosures.

References:

https://clinicaltrials.gov/show/NCT01235546

https://www.smfm.org/meetings/1-smfm-36th-annual-meeting