Improving Outcomes, Improving Throughput, Mythbusting

Pregnancy & Pyelonephritis…

You are seeing a twenty-something female, who presents for back pain & abdominal pressure x 3 days, and “felt warm” today.  You quickly diagnosis her with pyelonephritis, complicated by her new diagnosis of pregnancy.  After an ultrasound confirms viability and estimates a 15 week old fetus, you now have to decide treatment and disposition.  A 2014 review of pyelonephritis in pregnancy (from 1993-2010 in the Kaiser Permanente system) found pyelonephritis was more likely to occur in the African American or Hispanic population, those under 18 years old, less educated, nulliparous, those who initiated prenatal care late, and smoked during pregnancy.  Septicemia was quite low (1.9% vs 0.03%), as was acute pulmonary insufficiency (0.5% vs 0.04%) and acute renal dysfunction (0.4% vs 0.03%).  Spontaneous preterm birth (10.3% vs 7.9%) was somewhat higher in the pyelonephritis group, though most of the preterm births occurred between 33-36 weeks.

So then how do we treat these patients?

Let’s look at a few studies:
Study #1
179 women <24 weeks gestation randomized to 1) IV ampicillin & IV gentamicin 2) IV cefazolin or 3) IM ceftriaxone.  After one afebrile day, patients were then provided 10 days of keflex.  The three arms were similar in age, parity, temperature, gestational age, and initial WBC.  There was no statistically significant differences in LOS, hours to defervescence, resolution of CVA tenderness, or birth outcomes among the three treatment arms.  Positive blood cultures were found 8.4% of the time.

Study #2:
RCT of women <24 weeks pregnant with pyelonephritis were randomized to either: three daily 2 gram IV doses of cefazolin (88 patients) or a single daily IV dose of 1 gram ceftriaxone along with two additional doses of normal saline solution (90 patients).  All infusions were given on an 8-hour schedule.  Treatment continued until the patient became afebrile and were discharged on antibiotics based on culture & sensitivity.   Patient demographics and presenting signs and symptoms were similar in both groups.  There were no differences noted between the two treatment arms in regards to morbidity, LOS, treatment failure, or febrile days.

Study #3
RCT of women <24 weeks pregnant with pyelonephritis comparing 60 inpatients treated with IV cefazolin until afebrile for 48 hours vs 60 outpatients received two injections of IM ceftriaxone, both followed by a 10-day course of cephalexin.  Both groups were similar with respect to age, parity, temperature, estimated gestational age, initial WBC, and incidence of bacteremia.  Three patients in each group had recurrent pyelonephritis.  Six inpatients were switched to gentamicin: two because of a worsening clinical picture and four due to  a prolonged febrile course; no outpatients required a change in antibiotic.

Study #4
Ninety pregnant women admitted with a diagnosis of pyelonephritis and randomized to either 500 mg of oral cephalexin every 6 hours or to intravenous cephalothin 1 gram every 6 hours.  There was no difference between the oral and IV groups concerning predefined criteria for successful therapy (91.4% versus 92.9% successful therapy, respectively).  No characteristic available at presentation predicted bacteremia or ultimate failure of therapy.

Conclusions? IV cefazolin, IV ampicillin / IV gentamicin, and IM / IV ceftriaxone are all equivalent to each other in the patient population for study one & two.  Study three suggests that IM ceftriaxone x 2 doses (once in the ED, another the following day at an infusion center or in the ED) is equivalent to IV cefazolin for the treatment of pyelonephritis in pregnancy <24 weeks, and as we’ve stated in the past, IV vs PO antibiotics are likely equivalent as study 4 suggests.
Septicemia in pregnancy is quite low at 2%, but if you think your pregnant patient is truly ill, then feel free to keep them in observation, as patients likely improve with a day or so of antibiotics anyway.  However, be confident that if patients are going to fail therapy, the difference between an oral medication and its IV counterpart is minimal at best.  The risk of spontaneous preterm birth goes up to about 10% from 8%, but choice of antibiotic does not seem to affect this.  Bottom line, if the patient looks well, and feels well, they can probably go home if they are agreeable to return for any decline (or failure to improve).
http://www.ncbi.nlm.nih.gov/pubmed/9699761
http://www.ncbi.nlm.nih.gov/pubmed/7675380
http://www.ncbi.nlm.nih.gov/pubmed/7847521
http://www.ncbi.nlm.nih.gov/pubmed/24100227
http://www.ncbi.nlm.nih.gov/pubmed/2193265

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