1. Post cesarean Infection
Mahin Jamshidi MD
Professor Of Infectious Disease
IRAN UNIVERSITY OF MEDICAL SCIENCES
2019

2. Background
Surgical site infection (SSI) is the most common complication post cesarean delivery
The rate of SSI ranges from 3% to 15% worldwide.
infection occurring within 30 days from the operative procedure in the part of the body where the surgery took place.

3. Background
The risk for developing SSI has significantly decreased in the last three decades,
Improvements in hygiene conditions,
Antibiotic prophylaxis
Sterile procedures Despite this decrease, the occurrence of SSI is expected to increase given the continuous rise in the incidence of cesarean deliveries.

4. Genitourinary tract microbiology
Gram positive aerobic
Gram negative aerobic
Anaerobic
Mycoplasma
Other
GBS
E. coli
Peptostreptococcus
Chlamydia
S. auerus
Klebsiella
Peptococcus
Ureaplasma
Enterococcus
Proteus
Bacteroides
Pseudomonas
Gardnerella
Enterobacter
Colestridium
Bacteria encountered in the female genital tract can be divided into aerobic and anaerobic organisms.
This is a list of commonly found bacteria – some are more common than others, but in general it is important to remember that most GU infections are polymicrobial in nature and any combination of the above organisms can be implicated in peripartum infections.
Gibbs, Am J Obstet Gynecol 1987

5. Risk Factors for SSI Saed et al, Am J Infect Cont, 2019 Induction
Chorioamnionitis (Triple I, IAI)
Cesarean with labor
Spontaneous
Induction
Emergency cesarean without labor
Maternal comorbidities
Diabetes
Autoimmune conditions
Preeclampsia
Saed et al, Am J Infect Cont, 2019

6. Risk Factors for SSI ●Prolonged labor ●Prolonged rupture of membranes
●Multiple cervical examinations
●Internal fetal or uterine monitoring
●Large amount of meconium in amniotic fluid
●Manual removal of the placenta
●Low socioeconomic status
●Operative vaginal delivery
●HIV infection
●Colonization with group B Streptococcus 
● Bacterial vaginosis

7. deep SSI, involving fascial and muscle layers.
Definition Of SSI
It divides SSIs into:
incisional SSI
organ/space SSI.
Incisional SSI :
superficial, involving the skin and subcutaneous tissue
deep SSI, involving fascial and muscle layers.

8. Septic thrombophlebitis Abdominal abscess
organ/space SSI.
Endometritis
Septic thrombophlebitis
Abdominal abscess

9. Post cesarean infectious
SSI includes
Wound infection
Endometritis
Necrotizing fasciitis
Septic thrombophlebitis

10. outside uterine Infection
UTI
Aspiration Pneumonia…

11. wound infection localized erythema,
Clinical manifestations Symptoms include
localized erythema,
induration, warmth, and pain at the incision site.
Purulent wound drainage and separation of the wound.
systemic fever and leukocytosis.
diagnosis  of wound infection is clinical.

12. Endometritis
Postpartum endometritis refers to infection of the decidua It is a common cause of postpartum fever and uterine tenderness

13. Endometritis
The potential for infection is enhanced at least 10-fold in cesarean deliveries compared with vaginal births
because of the presence of foreign bodies (eg, suture material), myometrial necrosis at the suture line, and formation of hematomas and seromas.

14. 1.7 percent for those performed electively Cesarean
Epidemilogy
the frequency of postpartum endometritis is 11 percent for cesareans performed after the onset of labor and
1.7 percent for those performed electively Cesarean

15. Late onset postpartum endometritis
 Most cases of endometritis develop within the first week after delivery
15 percent present between one and six weeks postpartum Delayed presentation is more common after vaginal than cesarean delivery, and may present as late postpartum hemorrhage

16. Endometritis
Mild and cured with antibiotic therapy, extension of infection to the peritoneal cavity can result in peritonitis, intraabdominal abscess, or sepsis.
Necrotizing myometritis, necrotizing fasciitis of the abdominal wall, septic pelvic thrombophlebitis, and toxic shock syndrome are rare complications.

17. CLINICAL FINDINGS Endometritis
Postpartum fever, tachycardia that rise in temperature, midline lower abdominal pain, and uterine tenderness.
Purulent lochia, chills, headache, malaise, and/or anorexia are additional findings observed in some women
excessive uterine bleeding

18. Endometritis with toxic shock syndrome
  Although rare, clostridia, streptococci, and staphylococci can lead to endometritis with toxic shock syndrome and other serious complications (eg, necrotizing myometritis, necrotizing fasciitis).
This diagnosis is made in the following settings:

19. GroupA Streptococcus (GAS)
 patients with early-onset infection (within the first 48 hours postpartum)
High fever (>38.5°C).
Hypotension
Involvement of at least two other organ systems (eg, renal, liver, or pulmonary insufficiency; coagulopathy; soft tissue necrosis; erythematous macular rash with desquamation) suggests toxic shock syndrome.

20. Staphylococcal toxic shock syndrome
High fever >38.9°C,
hypotension, diffuse
erythroderma, desquamation
involvement of at least three organ systems.
Onset may be early (within 24 hours of delivery) and difficult to distinguish from GAS toxic shock.

21. C. sordellii Absence of rash or fever,
lethal toxic shock-like syndrome.
less than one week postpartum when they had sudden onset of clinical shock:
Progressive,
Refractory hypotension
Massive and generalized tissue edema,
hemoconcentration,
Marked leukemoid reaction (total neutrophil count 66,000 to 93,600/mm3), 
Absence of rash or fever,
limited or no myonecrosis, and a rapidly lethal course. 

22. C. perfringens
 has been found in necrotizing endomyometritis and fatal toxic shock after medical abortion
Should be considered in patients who rapidly become gravely ill with evidence of intravascular hemolysis that can be extreme.
It can cause Clostridial myonecrosis (gas gangrene), a life-threatening muscle infection that can be identified by radiographic imaging.

23. Diagnostic criteria for postpartum endometritis
  clinical
postpartum fever that cannot be attributed to another etiology after a thorough history and physical examination.
oral temperature of ≥38.0°C (≥100.4°F) on any two of the first 10 days postpartum,
Exclusive of the first 24 hours
low grade fever during this period is common and often resolves spontaneously, especially after vaginal birth.

24. The presence of one or more of the clinical findings described above (eg, tachycardia, midline lower abdominal pain, uterine tenderness, leukocytosis) supports the diagnosis,
but these findings are nonspecific. In particular, variable degrees of midline abdominal pain, uterine tenderness, and leukocytosis are common after cesarean delivery, and to a lesser extent after vaginal delivery, in the absence of infection. Some degree of malodorous yellow-red lochia is also normal after any delivery

25. Diagnostic criteria for postpartum endometritis
The presence of "Maternal Early Warning Criteria" (table 1) suggests that the patient is at risk for serious maternal morbidity and mortality and should be evaluated promptly Sepsis should be considered in these critically ill women, even if afebrile

26. Maternal Early Warning Criteria
BP <90
HR>120
RR>30
Urin out put < 350 cc 2 hrs
O2 Saturation <95%

27. ROLE OF CULTURES 
Blood(immunocompromised, septic, or fail to respond to empiric therapy)
Cervix – Cervical specimens for gonorrhea and chlamydia testing is not indicated
Endometrium – Endometrial cultures are not performed routinely because of the difficulty in obtaining an uncontaminated specimen through the cervix
Urin -Absess

28. Necrotizing fasciitis
Necrotizing fasciitis is a rare but serious infection causing significant morbidity after CD
Necrotizing fasciitis is suspected with:
severe pain,
crepitus, wooden-hard induration of the subcutaneous tissues, bullous lesions, skin necrosis or ecchymosis,
and
elevated serum creatine kinase level; a hallmark of necrotizing

29. Necrotizing fasciitis Diagnosis
fasciitis is rapid progression of clinical manifestations
Imaging studies such as
computed tomography or
magnetic resonance imaging may show edema extending along the fascial plane
The diagnosis is confirmed at the
time of repeat surgery

30. Septic pelvic thrombophlebitis
(SPT) is a rare condition that occurs in the setting of
pelvic vein, endothelial damage
venous stasis,
hypercoagulability

31. SPT can present with two somewhat distinctive syndromes.
Ovarian vein thrombophlebitis
usually ill, fever and abdominal pain within one week after delivery or surgery;
thrombosis of the ovarian vein (usually on the right side) can sometimes be visualized radiographically.

32. Patients with deep SPT present more subtly
Isolated fever in the early postpartum or postoperative period
Do not have abdominal or pelvic tenderness
Radiographic imaging typically does not identify thrombosis of a specific vein

33. Septic pelvic thrombophlebitis
SPT should be suspected in patients who have persistent fever despite antibiotic therapy
(usually for presumptive endometritis or other pelvic infection) in the few weeks following vaginal delivery, cesarean delivery, or pelvic surgery

34. TREATMENT Intravenous regimens
Clindamycin 900 mg every eight hours PLUS
Gentamicin 5 mg/kg every 24 hours (preferred) OR 1.5 mg/kg every 8 hours
cefotetan, cefoxitin,
ceftizoxime, piperacillin with or without tazobactam, and ampicillin-sulbactam ]
the initial antibiotic choice in some hospitals.

35. TREATMENT
Metronidazole provides good activity against most anaerobes and can be useful with ampicillin and gentamicin, but is not the preferred choice for breastfeeding women if a drug with a better safety profile is available.

36. GBS positive patients
  Resistance to clindamycin in invasive GBS isolates ranges from 13 to 43 percent For those patients who are known to be colonized with GBS as a result of universal screening,
Addition of ampicillin to a clindamycin- plus-gentamicin regimen or use of ampicillin-sulbactam (3 g IV every six hours) is recommended.

37. Bacteroides fragilis clindamycin resistance — 
In geographic regions or institutions where B. fragilis has significant clindamycin resistance, ampicillin- sulbactam (3 g IV every six hours) is a reasonable alternative

38. Duration IV Therapy
  Intravenous treatment until the patient is clinically improved (no fundal tenderness) and afebrile for 24 to 48 hours.
Oral antibiotic therapy after successful parenteral treatment is not required

39. Oral and intramuscular regimens
Clindamycin 600 mg orally every 6 hours plus gentamicin 4.5 mg/kg intramuscularly every 24 hours OR
●Amoxicillin-clavulanic acid 875 mg orally every 12 hours OR
●Cefotetan 2 g intramuscularly every 8 hours OR
●Meropenem or imipenem-cilastatin 500 mg intramuscularly every 8 hours OR
●Amoxicillin 500 mg plus metronidazole 500 mg orally every 8 hours

40. Duration Oral Therapy 14 day.
If an intramuscular antibiotic regimen is used, we suggest 48 to 72 hours of intramuscular therapy
then switch to an oral antibiotic to complete a seven day course.

41. Persistent postpartum fever
  resistant organisms Vancomycin 
Other etiologies of fever
physical examination to look for non-uterine sources of infection and worsening pelvic findings (eg, new mass, worsening pain).
Imaging. Sonography is useful for visualizing pelvic abscesses and fluid collections, but insensitive for diagnosis of septic pelvic thrombophlebitis or ovarian vein thrombosis where computed tomography (CT) or magnetic resonance imaging (MRI) are more helpful.

42. Relapse of endometritis
 — For patients who present with recurrent signs/symptoms of endometritis after having been treated for endometritis on initial hospitalization,
we suggest change of antibiotics from the initial regimen and further evaluation, as outlined above.

43. SPT Treatment
We suggest systemic anticoagulation for patients with suspected, presumptive, or documented SPT).
The duration of anticoagulation depends on the clinical presentation.
For patients who do not have documented thromboses or underlying hypercoagulable state, we discontinue anticoagulation 48 hours after the resolution of fever
For patients who have radiographic evidence of pelvic branch vein thromboses, we continue anticoagulation for at least two weeks.
For patients who have radiographic evidence of extensive pelvic thromboses (eg, thrombosis involving the ovarian vein, iliac veins, or vena cava) or septic emboli, we continue anticoagulation for at least six weeks

44. Prophylaxis Preoperative vaginal prep Pre-incision antibiotics
Gentle cord traction vs. manual removal
Subcutaneous closure > 2 cm
Suture skin closure
Antibiotics in special circumstances
CS after labor, ROM
Obesity
Chorioamnionitis (Triple I, etc.)
Sood, Curr Opin Infect Dis 2018,

45. Pre-incision Antibiotics
Therapeutic tissue levels at time of microbial contamination
Agent of choice
Long acting
Narrow focus on likely bacteria
Inexpensive
Few adverse effects

46. Antibiotics for Cesarean
1st generation cephalosporin is first line for all patients undergoing CS
< 60 mins prior to incision
1 g for patients < 80 kg
2 g for patients > 80 kg
3 g considered for patients > 120 kg
Azithromycin for non-elective CS
MRSA – add vancomycin to preop abx
IAI
Give one dose after CS
Add clindamycin or metronidazole

47. Standard Antibiotic Prophylaxis for CS
Cefazolin 1 g IV for patients < 80 kg
Timing
< 60 min before incision
Re-dose
Surgery more than 4 hours Blood loss greater than 1500 ml
Allergy
Clindamycin 900 mg
Gentamycin 5 mg/kg
Multi dose No
ACOG, PB 132, 2018

48. Adjunctive Azithromycin for non-elective cesarean

49. Infectious Morbidity Tita, A et al, NEJM 2016* * *

50. Post-cesarean Oral Antibiotics
RCT of PO cephalexin & metronidazole vs placebo for prevention of SSI in women with BMI > 30
Cefazolin 500 mg + metronidazole 500 mg or placebo Q 8hours for 48 hours
Standard preoperative IV antibiotics
Primary outcome
superficial incisional, deep incisional, or organ space infections
Stratified by membrane status
Mean BMI 40
Traditionally, antibiotic prophylaxis has not been continued postpartum because trials in general surgical populations showed no benefit.
Now, a randomized trial of oral cephalexin plus metronidazole for 48 hours following cesarean delivery in women with a BMI > 30 found a 60 percent reduction in surgical site infections compared with placebo . But does this mean that we should start treating all patients with cesarean section with 48 hours of PO abx?

51. Post-Cesarean Cephalexin and Metronidazole
Ruptured Membranes
C/M (n = 63)
Placebo (n = 63)
RR (95% CI) P
SSI
6 (9.5)
19 (30.2)
0.31( )
.008
Intact Membranes
C/M (n = 138)
Placebo (n = 139)
RR (95% CI) P
SSI
7 (5.0)
12 (8.7)
0.58 ( )
.47
Briefly, obese patients were randomized to either receive standard preoperative Ancef alone, or additionally – oral Keflex and metronidazole for 48 hours following cesarean.
patients were also stratified based on intact vs ruptured membranes.
Primary outcome was surgical site infection.
382 Patients participated. The mean BMI was 40. Overall rate of SSI was about 11%, and even higher rates of 20% were observed among those with ruptured membranes vs 7% among those with intact membranes.
In the Control group, SSI was 15%. In the Treatment group, it was 6.4%. The relative risk was 0.41 and statistically significant.
Valent et al. JAMA 2017

52. Vaginal Cleansing Meta-analysis and Systematic Review, 2017
Outcomes
Vaginal Cleansing
Controls
RR (95% CI)
Endometritis
4.5%
8.8%
0.52 (0.37–0.72)
Postoperative fever
9.4%
14.9%
0.65 (0.50–0.86)
Vaginal cleansing resulted in less endometritis among subgroups
Laboring patients
Patients with ROM
Povidone-iodine solution (not CHX)
Preoperative antibiotics

53. Skin Antisepsis Tuuli MG, NEJM, 2016
RCT of chlorhexidine alcohol vs iodine-alcohol
572 women in CXH group
575 in IOD group
Primary outcome
Superficial or deep wound infection within 30 days

54. Skin Antisepsis Tuuli MG, NEJM, 2016

55. Peri-operative antibiotics for Cesarean in the setting of Triple I, IAI, Chorioamnionitis
We have established that the administration of perioperative cesarean antibiotics reduces postoperative infectious morbidity. Is one particular agent is superior? Many different drug regimens have been reported to be effective in decreasing immediate postoperative infectious morbidity, and this includes various PCNs, cephalosporins fluoroquinolones, among other antibiotic classes. .
in the setting of triple-I (chorio), do we need to add Ancef at time of cesarean delivery?

56. Cesarean Prophylaxis and IAI
If the patient is already receiving broad spectrum antibiotics for another indication (IAI, pyelo, etc), additional cefazolin is not necessary
One additional dose of chosen regimen should be given after cesarean
PLUS Clindamycin 900 mg IV or metronidazole 500 mg IV for at least one dose
ACOG CO 712, 2017 ACOG PB 199, 2018

57. Treatment for Chorio, IAI, Triple I ACOG CO 712, 2017
Recommended Abx
Ampicillin
2g IV Q 6 hours
Gentamicin
2 mg/kg followed by 1.5 mg/kg Q 8 hours or
5 mg/kg Q 24 hours
Mild PCN Allergy*
Cefazolin
2g IV Q8 hours
Severe PCN Allergy*
Clindamycin or
900 mg IV Q8 hours
Vancomycin
1 g IV Q12 hours
In the interest of time, I will skip over the criteria used to diagnose triple-I. However, Most patients with triple-I typically have a polymicrobial infection, often involving vaginal or enteric flora. Two-thirds of women with triple-I have at least two isolates per specimen of amniotic fluid.
The optimal antibiotic regimen for triple-I has not been well-studied and current recommendations are based largely on the results of a 2002 Cochrane review. A typical regimen includes ampicillin every 6 hours and gentamicin every 8–24 hours until delivery. If cesarean delivery is performed, administration of clindamycin or metronidazole is recommended at time of delivery, and for an additional 24 hours. This adds anaerobic coverage.
*Substitute for ampicillin. Gentamicin in all of these regimens

58. Treatment for Chorio, IAI, Triple I ACOG CO 712, 2017
Alternative Regimens
Ampicillin/Sulbactam
3 g IV Q 6 hours
Piperacillin-tazobactam
3.375 Q 6 hours or 4.5 g Q 8 hours
Cefotetan
2 g IV Q 12 hours
Cefoxitin
2 g IV Q 8 hours
Ertapenum
1 g IV Q 24 hours
In the interest of time, I will skip over the criteria used to diagnose triple-I. However, Most patients with triple-I typically have a polymicrobial infection, often involving vaginal or enteric flora. Two-thirds of women with triple-I have at least two isolates per specimen of amniotic fluid.
The optimal antibiotic regimen for triple-I has not been well-studied and current recommendations are based largely on the results of a 2002 Cochrane review. A typical regimen includes ampicillin every 6 hours and gentamicin every 8–24 hours until delivery. If cesarean delivery is performed, administration of clindamycin or metronidazole is recommended at time of delivery, and for an additional 24 hours. This adds anaerobic coverage.