Antibiotics Used for Urinary Tract Infections in Pregnancy

Antibiotics Used for Urinary Tract Infections in Pregnancy: History

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Subjects: Urology & Nephrology

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Urinary tract infection (UTI) is considered to be a major problem in pregnant women. It is also one of the most prevalent infections during pregnancy, being diagnosed in as many as 50–60% of all gestations. Therefore, UTI treatment during pregnancy is extremely important and management guidelines have been published worldwide to assist physicians in selecting the right antibiotic for each patient, taking into account the maternal and fetal safety profile.

urinary tract infection
UTI
pregnancy
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guideline

1. Introduction

Urinary tract infection (UTI) is considered to be a major problem in pregnant women [1,2,3]. It is also one of the most prevalent infections during pregnancy, being diagnosed in as many as 50–60% of all gestations [4].

UTIs can be classified as lower urinary tract infections, including both asymptomatic bacteriuria (ASB) or acute cystitis (AC), and upper urinary tract infections or acute pyelonephritis (APN) [5]. Most infections are caused by Enterobacteriaceae, commonly found in the gastrointestinal tract, with Escherichia coli (E. coli) being responsible for 80–90% of cases. However, we can find other bacteria such as Group-B Streptococcus saprophyticus (GBSS), Klebsiella pneumoniae, coagulase-negative Staphylococcus, Staphylococcus aureus and Proteus mirabilis in a lower percentage [2,6].

In pregnant women, ASB occurs in an estimated 2–10% [7], and if left untreated, it can turn into symptomatic AC in 30% of patients and may progress to APN in up to 50% of those patients [6], which have been associated with several complications for both the mother and the unborn child [2,8].

Therefore, UTI treatment during pregnancy is extremely important and management guidelines have been published worldwide to assist physicians in selecting the right antibiotic for each patient, taking into account the maternal and fetal safety profile [5,6,9].

2. Antibiotics in ABU

Without specifying the hierarchy of preference, the recommended antibiotics were: nitrofurantoin [11,15,18,19,20], trimethoprim/sulfamethoxazole (TMP/SMX) [20], fosfomycin [11,12,13,15,19], multiple penicillins such as amoxicillin [15,19,20], ampicillin [18], pivmecillinam [11], ampicillin/sulbactam [21], amoxicillin/clavulanate [15,20,21], first-generation cephalosporine (1stGC) such as cephalexin [15,18,19,20,21] and second-generation cephalosporine (2ndGC) such as cefuroxime [15,19].

When referring to lines of treatment, as first line, nitrofurantoin [16,21], fosfomycin [21] and amoxicillin [14] were proposed. Second-line treatments were pivmecillinam [14], cephalexin [16] and amoxicillin (if sensible) [16]. France was the only country that gives up to five-line treatments [14], with fosfomycin being the third-line treatment; trimethoprim, the fourth-line one; and nitrofurantoin, amoxicillin/clavulanate, cefixime and TMP/SMX, the fifth-line treatment. TMP/SMX was also suggested as the last antibiotic choice in Germany [11].

Results are summarized in Table 3, including the dosage recommended by each guideline.

Table 3. Antibiotic treatment for asymptomatic bacteriuria and cystitis during pregnancy.

	Asymptomatic Bacteriuria			Cystitis
Antibiotic (Oral)	Treatment Line: Country/Region	Dosage (Guideline Reference)	Duration (Days)	Treatment Line: Country/Region	Dosage (Guideline Reference)	Duration (Days)
Nitrofurantoin	1st Line: UK, CO 5th Line: FR NS: DE, IE, USA, AR, BR	100 mg/6–8 [19,20,21] 100 mg/12 h * [11,15,16,21] or 50 mg/6 h [11,16]	5–7 5–7 7	1st Line: UK, DE, CO 3rd Line: FR NS: DE, IE, AR, BR	100 mg/6–8 [19,20,21] or 100 mg/12 h * [11,15,16] or 50 mg/6 h [11,16]	5–7 5–7 7
Amoxicillin	1st Line: FR 2nd Line: UK NS: IE, AR, BR	500 mg/8 h [15,16,19] or 875 mg/12 h [19]	5 or 7 7	1st Line: UK 2nd Line: AU NS: IE	500 mg/8 h [15,16,22]	5 or 7
Cephalexin (1stGC)	2nd Line: UK NS: IE, USA, AR, CO, BR	500 mg/6–8 h [19,20,21] or 500 mg/8–12 [15,16]	5–7	1st Line: AU 2nd Line: UK NS: IE, AR, CO	500 mg/6–8 h [20,21] or 500 mg/8–12 h [15,16,22]	5–7
Pivmecillinam	2nd Line: FR N.S: DE	400 mg/8–12 h [11]	3 or 7	2nd Line: FR NS: DE	400 mg/8–12 h [11]	3 or 7
Fosfomycin	1st Line: CO 3rd Line: FR NS: IE, DE, EU, CH, ES, BR	3 g [7,11,12,13,14,15,19,21]	Single dose	1st Line: FR, CO NS: IE, DE, EU, UK, ES, AR, BR	3 g [7,11,13,14,15,16,21]	Single dose
Trimethoprim	4th Line: FR	N.A	7	1st Line: AU	300 mg/24 h [22]	3
Amoxicillin/ clavulanate	5th Line: FR NS: IE, AR, CO	875 mg/12 h [20] or 500 mg/8 h [21] or 625 mg/8 h [15]	5–7	1st Line: CH 2nd Line: AU NS: IE, CO, BR	500/125 mg/12 h [19,22] or 875/125 mg/12 h [19] or 500 mg/8 h [21] or 625 mg/8 h [12,15]	5–7
Cefixime (3rdGC)	5th Line: FR	N.A	7	3rd Line: FR	N.A	7
TMP/SMX	5th Line: FR Last line: DE NS: AR	800/160 mg/12 h [11,20]	4–7	3rd Line: CH Last line: DE	800/160 mg/12 h [11,12]	4–7
Cefuroxime (2ndGC)	NS: IE, BR	250–500 mg/12 h [19] 500 mg/12 h [12]	5–7	2nd Line: CH NS: IE, BR	250 mg/12 h [19] 500 mg/12 h [12,15]	5–7
Ampicillin/ sulbactam	NS: CO	1.5 g/12 h [21]	5–7
Ampicillin	NS: USA	N.A	4–7
Ciprofloxacin	-	-	-	3rd Line: FR	N.A	5–7

NS: Not specified; *: Macrocrystals/Prolonged release; 2ndGC: Second-generation cephalosporin; TMP/SMX: Trimethoprim/Sulfamethoxazole; EU: Europe; CO: Colombia; FR: France; UK: United Kingdom; DE: Germany; IE: Ireland; USA: United States of America; AR: Argentina; BR: Brazil; CH: Switzerland; ES: Spain; AU: Australia.

3. Antibiotics in Cystitis

Without specifying the hierarchy of preference, the recommended antibiotics were: nitrofurantoin [11,15,19,20], fosfomycin [7,11,13,15,16,19,20], multiple penicillins such as amoxicillin [15], pivmecillinam [11], amoxicillin/clavulanate [15,19,21], 1stGC (cephalexin) [15,20,21] and 2ndGC (cefuroxime) [15,19].

When referring to lines of treatment, as first line, nitrofurantoin [11,16,21], fosfomycin [14,21], trimethoprim [22], cephalexin [22], amoxicillin [16] and amoxicillin/clavulanate [12] were proposed. For second-line treatment the chosen antibiotics were pivmecillinam [14], cephalexin [16], penicillins such as amoxicillin [22] and amoxicillin/clavulanate [22] and 2ndGC (cefuroxime) [12]. For third-line treatment, options were nitrofurantoin [14], ciprofloxacin [14], TMP/SMX [12] and third-generation cephalosporine (3rdGC) such as cefixime [14]. TMP/SMX was also suggested as the last antibiotic choice in Germany [11].

Results are summarized in Table 3, including the dosage recommended by each guideline.

4. Antibiotics in APN

For APN treatment, most guidelines recommended as a first-line treatment a monotherapy with 3rdGC [13,14,15,20] such as ceftriaxone [15,20] or 2ndGC [7,13] such as cefuroxime [13,17] and, if patient unstable or septic, adding an aminoside such as gentamicin [7,13,15] was recommended. Double parental therapy with amoxicillin/gentamicin [7,22] or ampicillin/gentamicin [22] was also proposed.

Second-line treatment included cefuroxime [12], gentamicin [20], aztreonam [7,20], 2ndGC such as cefuroxime [12] and 3rdGC (ceftriaxone or cefotaxime) [22]. Ireland proposed a dual parenteral therapy with clindamycin or vancomycin (based on the susceptibly results) and gentamicin.

As a third-line option, France proposed ciprofloxacin in case of beta-lactamase allergy [14]. The AFU also specified a 10 day-treatment for UTI caused by extended-spectrum beta-lactamase producing E. coli (ESBLE). Ciprofloxacin, levofloxacin or TMP-SMX was the first-line choice, amoxicillin–clavulanate was the second-line choice and cefoxitin, piperacillin–tazobactam or temocillin was the third-line choice.

Recommendations for oral therapy switch were: amoxicillin [14,22], amoxicillin/clavulanate [14,22], cephalexin [22], trimethoprim [22], cefixime [14] or ciprofloxacin [14].

A couple of European guidelines proposed oral antibiotics for uncomplicated AP: cephalexin (1stGC) [17] or amoxicillin/clavulanate [12] as a first-line treatment and TMP/SMX [12] as third-line treatment.

Results are summarized in Table 4, including the dosage recommended by each guideline.

Table 4. Antibiotic acute pyelonephritis during pregnancy.

Antibiotic	Treatment Line: Country/Region	Dosage (Guideline Reference)	Duration (Days) *	Remarks (Guideline Reference)
Ceftriaxone IV	1st Line: IE, FR, AR, ES 2nd Line: AU	1–2 g/24 h [14,15,22] 1–2 g/24 h [13,20]	10–14 or 7–10	If patient unstable: add G (i.e., es) [13,15] If contraindication for G [22] Consider 2 g dose in 2nd/3rd T of pregnancy [15]
Amoxicillin + Gentamicin IV	1st Line: AU, EU	Ax: 2 g/6 h [7,22] G: 5 mg/kg/24 h [7,22]	7–14
Ampicillin + Gentamicin IV	1st Line: AU	Ap: 2 g/6 h [22] G: 5 mg/kg/24 h [22]	10–14
2ndGC ± Aminoside IV	1st Line: EU	N.A	7–14	If sepsis: add aminoside [7]
Cephalexin (1stGC) PO	1st Line: UK	500 mg/8–12 h [17]	7–10
Amoxicillin/Clavulanate PO	1st Line: CH	1 g/12 h or 625 mg/8 h [12]	5–7
Cefuroxime (2ndGC)	1st Line: UK, ES 2nd Line: CH	750 mg–1.5 g/6–8 h [17] or 500 mg/12 h [12]	7–10 3–5	If PO is not suitable [17] If sepsis: add aminoside [13]
Ciprofloxacin	2nd Line: FR	NA	7–14
Clindamycin + Gentamicin IV	2nd Line: IE	C: 900 mg/8 h G: 1.5 mg/kg/8 h or 5 mg/kg/24 h [15]	10	If GBSS: choose vancomycin (1 g/12 h) or clindamycin based on the susceptible results [15]
Cefotaxime IV	2nd Line: AU	1 g/8 h [22]	10–14	If contraindication for G [22]
Gentamicin IV/IM	2nd Line: AR	240 mg/24 h [20]	10	If allergy to beta-lactams [20]
Aztreonam IV	2nd Line: AR, EU	1–2 g/8–12 h [20]	10	If allergy to beta-lactams [20]
TMP/SMX	3rd Line: CH	800/160 mg/12 h [12]	3–5

EU: Europe; FR: France; UK: United Kingdom; DE: Germany; IE: Ireland; AR: Argentina; CH: Switzerland; ES: Spain; AU: Australia; G: Gentamicin; 2nd/3rd T: Second/Third trimester; *: days of parenteral + oral treatment.

This entry is adapted from the peer-reviewed paper 10.3390/jcm11237226

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