Drugs And Pregnancy Part 3

Although there are no such reports, vancomycin could theoretically result in the same toxicity in the fetus, since this drug readily crosses the placenta.

Aztreonam Aztreonam belongs to a relatively new cla.s.s of antibiotics: the mon.o.bactams. It is effective against most of the aerobic Gram-negative rods or Enterobacteriaceae, and is used as an alternative to the aminoglycosides. There are no well-controlled studies in pregnant humans. However, according to its manufacturer, aztreonam has not been shown to be teratogenic in several animal models given several times the human dose.

Moreover, a particular advantage of this antibiotic over the aminoglycosides is that it is not a.s.sociated with either nephrotoxicity or ototoxicity in either the mother or the fetus.

Imipenem Imipenem is a carbapenem antibiotic that is derived from thienamycin. It is presently combined with cilastatin, which inhibits the renal metabolism of imipenem. Cilastatin has no intrinsic antimicrobial activity. Imipenem is effective against a wide variety of 34 34 Antimicrobials during pregnancy Gram-positive and Gram-negative aerobic and anaerobic organisms. It has the potential to be very effective as single-agent therapy for polymicrobial pelvic infections in women.

There are no available human reproductive studies, but the imipenemcilastatin combination has not been shown to be teratogenic in rats or rabbits, according to its manufacturer. There are few indications for the use of this very 'potent' antibiotic in pregnant women. Potential maternal side effects include hypersensitivity, central nervous system toxicity, and pseudomembranous colitis.

Quinolones Ciprofloxacin, norfloxacin, and ofloxacin belong to the fluoroquinolone group of antibiotics. They are very effective against the aerobic Gram-negative bacilli, and hence are especially useful for the treatment of urinary tract infections. They also exhibit good activity against a variety of aerobic Gram-positive organisms, although most anaerobes are resistant to both antibiotics. They may also be effective against C. trachomatis C. trachomatis and and N. gonorrhoeae N. gonorrhoeae.

Among 549 pregnancies that were exposed to quinolones during the first trimester, there were the following exposures: 318 norfloxacin, 93 oflaxacin, 70 ciprofloxacin, and 57 pefloxacin (Schaefer et al et al., 1996). a.n.a.lyses controlled for various confounding factors, and it was found that the frequency of congenital anomalies was not increased above background (3.5 percent) for first-trimester exposure to quinolones except for ofloxacin.

However, two of the defects a.s.sociated with ofloxacin exposure were secondary to prematurity (undescended t.e.s.t.i.c.l.e and inguinal hernia). When these two infants were excluded from the a.n.a.lysis, the frequency of congenital anomalies was not increased above background. Hence it appears that quinolones do not pose a teratogenic risk.

Norfloxacin was not found to be teratogenic when given to monkeys during the critical period of organogenesis (Cukierski et al et al., 1989). However, according to the manufacturer, quinolones may cause lameness or irreversible arthropathy in immature dogs Box 2.13 Potential adverse fetal and maternal effects of Box 2.13 Potential adverse fetal and maternal effects of quinolones quinolones Fetal effects None known Irreversible arthropathy in immature animalsa Maternal effects Central nervous system toxicity *

headache *

dizziness *

insomnia Gastrointestinal intolerance *

nausea *

vomiting *

anorexia Hypersensitivity aCukiersi et al., 1989; Christian, 1996.

Antifungals 35.secondary to lesions in the cartilage (Box 2.13). Thus, this cla.s.s of drugs is not recommended for use during pregnancy. The few serious maternal side effects are summarized in Box 2.13. It should be noted that approximately 2 percent of women taking these drugs experienced a reversible skin rash and photosensitivity (Christian, 1996).

Naldixic acid, another quinolone, was a.s.sociated with pyloric stenosis but the relations.h.i.+p is apparently not causal. Although data are not adequate to exclude a risk of birth defects following exposure during the first trimester, it seems unlikely that naldixic acid poses a substantial risk of birth defects (Friedman and Polifka, 2006). Other quinolones have not been investigated for use during pregnancy: moxifloxacin (Avalox), gatifloxacin (Tequin), levofloxacin (Levaquin), garebixacin, and gemifloxacin.

Azithromycin No epidemiological studies of azithromycin use during pregnancy have been published.

Although, it does not seem to be a.s.sociated with a high risk of congenital anomalies following first-trimester exposure, a small risk cannot be excluded (Friedman and Polifka, 2006).

Ant.i.tuberculosis drugs There are several drugs utilized to treat tuberculosis. These are summarized in Box 2.14.

In a review of 15 studies involving 446 pregnancies exposed to rifampin, Snider and coworkers (1980) reported a malformation rate of 34 percent, similar to that of the general population. There were also over 600 pregnancies exposed to ethanbutol and almost 1500 exposed to isoniazid without evidence of an increase in congenital malformations (Snider et al et al., 1980). There is no information regarding the drug pyrazinamide during pregnancy. The maternal side effects are also listed in Box 2.14. More recently, thalidomide has been utilized for the treatment of tuberculosis, especially in HIV-infected patients (Kaplan, 1994; Klausner et al et al., 1996; Peterson et al et al., 1995; Tramontana et al et al., 1995). This most potent teratogen should obviously be avoided in pregnant women or those likely to become pregnant.

ANTIFUNGALS.

The more commonly used antifungal agents are summarized in Box 2.15. Many of these are for topical application.

Nystatin, clotrimazole, and miconazole These agents are utilized primarily for the treatment of candidiasis. In at least two recent reports there were no increases in malformations from their use (Jick et al et al., 1981; Rosa et al et al., 1987a).

Butoconazole, terconazole, and ketoconazole There are no large studies of the use of these three antifungal agents during pregnancy.

Butoconazole is a category B drug, and the other two are listed as category C by their 36 36 Antimicrobials during pregnancy Box 2.14 Potential adverse fetal and maternal effects of rifampin, ethambutol, isoniazid and pyrazinamide ethambutol, isoniazid and pyrazinamide Rifampin Isoniazid Fetal effects Fetal effects None known None known Maternal effects Maternal effects Discoloration of urine, feces, sweat, sputum, Gastrointestinal disturbance tears Hepat.i.tis Gastrointestinal intolerance Hypersensitivity Headache, fatigue, myalgia, fever Peripheral neuritis Hypersensitivity Pyrazinamide Ethambutol Fetal effects Fetal effects Unknown None known Maternal effects Maternal effects Arthralgias Hypersensitivity Elevated liver enzymes Hyperuricemia Gastrointestinal disturbance Optic and peripheral neuritis Rash Adapted in part from the USP DI (United States Pharmacopeial Convention, 2003); PDR, 2004.

manufacturers. It seems unlikely that these agents would have significant, if any, teratogenic risks.

Fluconazole Fluconazole is an azole antifungal similar to ketoconazole and is utilized for both local and systemic fungal infections (Hollier and c.o.x, 1995). It is useful in the treatment of v.a.g.i.n.al, oral, and systemic candidiasis, as well as for prophylaxis and treatment of cryp-tococcal infections in immunocompromised patients (i.e., HIV-infected). Among 239 women who took single low doses of fluconazole, 60 took it during the first trimester of pregnancy. None of the infants had any congenital anomalies (Inman et al et al., 1994).

Box 2.15 Antifungals Amphotericin B Ketoconazole Butoconazole Miconazole Ciclopirox Nystatin Clotrimazole Terconazole Fluoconazole Tolnaftate Griseofulvin Undecylenic acid From PDR, 2004.

Antifungals 37.However, four cases of craniosynostosis with radial-humeral bowing and tetrology of Fallot have occurred following repeated high-dose fluconazole for cocci meningitis (Aleck and Bartley, 1996; Lee et al et al., 1992; Pursley et al et al., 1996), although normal healthy children have been delivered following high-dose fluconazole treatment (Krcmery et al et al., 1995). In one study of 226 pregnancies exposed to fluconazole during the first trimester, the frequency of congenital anomalies was not increased (Mastroiacovo et al et al., 1996).

However, it should not be withheld in HIV-infected pregnant women who require cryp-tococcal prophylaxis. Maternal side effects may include headache, dizziness, or gastrointestinal upset.

Ciclopirox This is a relatively new, topical antifungal agent effective against various dermatophytes such as Trichophyton Trichophyton species and species and Candida albicans. Candida albicans. There is little, if any, information regarding its use during pregnancy but, according to its manufacturer, it was not teratogenic in various animal studies. It is a category B drug. There is little, if any, information regarding its use during pregnancy but, according to its manufacturer, it was not teratogenic in various animal studies. It is a category B drug.

Tolnaftate, undecylenic, and terbinafine Both tolnaftate (Tinactin) and undecylenic acid (Desenex) are utilized for dermatophyte infections such as tinea pedis and tinea corporis, but are not effective against yeast (Davis, 1995). Terbinafine (Lamisil) is a topical antifungal that is effective against most dermatophytes as well as most Candida Candida species (Davis, 1995; PDR, 2004). There are no reports of these agents being teratogenic, and it would seem reasonable to cla.s.sify them as category B agents at the present time. species (Davis, 1995; PDR, 2004). There are no reports of these agents being teratogenic, and it would seem reasonable to cla.s.sify them as category B agents at the present time.

Amphotericin B Amphotericin B is an antifungal agent that is used primarily to treat systemic mycotic infections. There are no adequately controlled studies of this agent during pregnancy.

However, in a review of case reports by Ismail and Lerner (1982), there was no evidence of teratogenicity of amphotericin B.

The potential adverse maternal effects of amphotericin B are summarized in Box 2.16.

Griseofulvin Griseofulvin is an antifungal agent used primarily to treat mycotic infections of the skin, nails, and hair. It is incorporated in the keratin of the epidermis and nails and is fungista-tic (Davis, 1995). There are no adequately controlled studies of this antifungal agent during pregnancy. However, Rosa and a.s.sociates (1987b) reported two cases of conjoined twins born to mothers who took griseofulvin during early pregnancy. A variety of central nervous system malformations and skeletal anomalies have been observed in the offspring of animals treated with several times the human dose of griseofulvin during pregnancy (Klein and Beall, 1972; Scott et al et al., 1975). Because of these reports, griseofulvin is not recommended for use during pregnancy. The potential maternal adverse effects are summarized in Box 2.16.

38.Antimicrobials during pregnancy Box 2.16 Potential adverse fetal and maternal effects of antifungal agents antifungal agents Nystatin, Clotrimazole, Miconazole, Gastrointestinal disturbance Butoconazole, Terconazole, Ketoconazole Fetal effects Amphotericin B None known Fetal effects None known Maternal effects Local irritation Maternal effects Anemia, agranulocytosis Ciclopirox, Tolnaftate, Undecylenic acid, Hypokalemia Terbinafine Hypersensitivity Fetal effects Polyneuropathy None known Central nervous system toxicity Renal failure Maternal effects Skin irritation Griseofulvin Fetal effects Fluoconazole None known (humans) Fetal effects None known; case reports of skeletal Maternal effects abnormalities Headaches, confusion Hepat.i.tis Maternal effects Hypersensitivity Headache Leukopenia Hypersensitivity Peripheral neuropathy Liver dysfunction Photosensitivity Adapted in part from the USP DI (United States Pharmacopeial Convention, 2003); PDR, 2004.

ANTIVIRALS.

Some of the more common antiviral agents are summarized in Box 2.17. Many of these agents are given for life-threatening illnesses.

Acyclovir and valacyclovir Acyclovir is an antiviral agent used primarily in the treatment and prophylaxis of herpes simplex infections. The active metabolite of valacyclovir is acyclovir, and the use of valacyclovir during pregnancy will have risks similar to those of acyclovir. It has also been used in the treatment of other herpes infections, including varicella. There are no well-controlled studies in pregnant humans. However, in one review of seven women who received acyclovir during the second half of pregnancy, there were no congenital abnormalities detected (Leen et al et al., 1987). Moreover, according to the manufacturer, acyclovir was not teratogenic in a variety of animals tested. In a review of 239 pregnancies in which acyclovir was utilized in the first trimester (Andrews et al et al., 1992), there Antivirals Antivirals 39.Box 2.17 Antiviral agents Amantadine Osteltamivir Acyclovir Penciclovir Cidofovir Ribavirin Didanosine (ddI) Stavudine (d4T) Docosanol Valacyclovir Famciclovir Vidarabine Famvir Zalcitabine (ddC) Foscarnet Zanamivir Ganciclovir Zidovudine Idoxuradine Box 2.18 Potential adverse fetal and maternal effects of antiviral agents agents Acyclovir and valacyclovir Maternal effects Fetal effects Anemia, granulocytopenia None known Gastrointestinal intolerance Headache, dizziness, insomnia Maternal effects Agitation, confusion, anxiety Hypersensitivity Hypersensitivity Acute renal failure Hematuria Idoxuridine Arthralgia Fetal effects Gastrointestinal intolerance None known (humans) Dizziness Insomnia Maternal effects Anorexia Hypersensitivity Famvir Amantadine Fetal effects Fetal effects None known None known Maternal effects Maternal effects None known Anticholinergic effects Leukopenia Ribavirin Orthostatic hypotension Fetal effects Gastrointestinal intolerance Unknown in humans Central nervous system toxicity Maternal effects Vidarabine Conjunctivitis Fetal effects Hypotension None known (humans) Zidovudine Maternal effects Fetal effects Hypersensitivity None known Adapted from Gilstrap et al., 1991.

40.Antimicrobials during pregnancy were 47 induced and 24 spontaneous abortions. Of 168 liveborn neonates, 159 had no congenital anomalies and of the nine neonates who did, no distinctive pattern of anomalies could be identified (Andrews et al et al., 1992). Acyclovir has also been used successfully during pregnancy to treat varicella pneumonia, disseminated herpes infection, and herpes hepat.i.tis (Johnson and Saldana, 1994; Petrozza et al et al., 1993; Zambrano et al et al., 1995). Recently, acyclovir has been used during the last 4 weeks of pregnancy to prevent recurrent herpes infections and prevent the need for cesarean delivery (Scott et al et al., 1996). The potential adverse maternal effects are summarized in Box 2.18.

Ganciclovir Ganciclovir is a nucleoside a.n.a.log similar to acyclovir. It has been shown readily to cross the human placenta (Gilstrap et al et al., 1994; Henderson et al et al., 1993). Ganciclovir is more toxic than acyclovir, and there is no information regarding its use during pregnancy.

Zidovudine (AZT) Zidovudine (Retrovir) is a thymidine a.n.a.log that inhibits viral replication by inhibiting DNA synthesis. It is used primarily in the treatment of the acquired immunodeficiency syndrome (AIDS) and may also be used as a 'prophylactic agent' to delay the onset of clinical disease or after accidental exposure to the AIDS virus. Zidovudine was not teratogenic in human or animal studies. Some of the maternal side effects secondary to the drug are difficult to distinguish from those caused by the disease process itself. The antepartum (as early as 14 weeks gestation) and intrapartum prophylactic use of this agent is currently recommended to reduce the frequency of perinatal HIV transmission to the fetus (ACOG, 1994; CDC, 1993). The risk of fetal HIV infection is substantially reduced in women carrying this virus who are treated with zidovudine during pregnancy (Lyall et al et al., 2001; Minkoff, 2001; Mofenson et al et al., 2002; Mueller and Pizzo, 2001; Watts, 2001). Zidovudine seems unlikely to be a.s.sociated with an increased risk of congenital anomalies and should be given for the treatment of HIV.

OTHER ANTI-HIV DRUGS.

Other anti-HIV drugs include nucleoside/nucleotide reverse transcriptase inhibitors (lamivudine, emtricitabine, zalcitabine, abacavir, tenofovir), protease inhibitors (aprenavir, indinavir, saquinavir, fosamprenavir, ritonavir, darunavir, atazanavir, nelfinavir), and non-nucleoside reverse transcriptase inhibitors (delaviridine, efavirenz, nevirapine).

A new type of anti-HIV drug is the 'entry inhibitors' that block HIV virus entry into the cell, and there is one currently available: enfuvirtide.

None of these drugs has been adequately studied during human pregnancy, but clearly the benefit (life-saving) of their use outweighs any theoretical risk.

Idoxuridine Idoxuridine is an ophthalmic antiviral agent used primarily for the treatment of herpes simplex eye infections. To date, there have been no reports of congenital anomalies in Antiparasitics Antiparasitics 41.infants born to women treated with this agent during pregnancy, but there have been no adequately controlled scientific studies in humans. Idoxuridine has been reported to be a.s.sociated with both eye and skeletal malformations in the offspring of pregnant rabbits who received this local antiviral agent in usual human doses (Itoi et al et al., 1975).

Amantadine Amantadine is an antiviral agent used in the treatment and prophylaxis of influenza.

There are no adequately controlled human studies. However, this particular agent was not shown to be teratogenic in rats or rabbits. Amantadine is rarely, if ever, indicated for use during pregnancy. Pandit and a.s.sociates (1994) did report that one of four fetuses exposed to amantadine had tetralogy of Fallot.

Vidarabine Vidarabine is a DNA inhibitor used systemically to treat disseminated herpes simplex infections and locally to treat herpetic ophthalmic infections. There are no adequate human studies available. However, Schardein et al et al. (1977) and Kurtz and a.s.sociates (1977) reported congenital anomalies in rats given several times the usual human dose.

Hillard and colleagues (1982) reported on the use of this drug late in pregnancy for disseminated herpes simplex infections.

Ribavirin Ribavirin is used primarily as an inhalation aerosol to treat respiratory syncytial virus (RSV) infection in infants and young children. Although there are no reports of congenital abnormalities in well-controlled human studies, ribavirin has been reported to cause a variety of congenital anomalies in commonly used laboratory animals (Ferm et al et al., 1978; Kilham and Ferm, 1977; Kochhar et al et al., 1980). Since RSV infections in pregnant women are generally self-limited and do not normally require treatment, and because of the significant teratogenicity of ribavirin in a variety of animals, this drug is listed as FDA Category X and is not recommended for use during pregnancy.

Other antivirals Other antivirals (idofovir, docosanol, famciclovir, penciclovir, foscarnet, valganciclovir, osteltamivir, zabamivir) have not been studied during pregnancy, or a.s.sessed for the possible a.s.sociation with birth defects following use during the first trimester.

ANTIPARASITICS.

Although parasitic infections are relatively common during pregnancy, therapy (with a few exceptions) can usually be withheld until after pregnancy since many such infections are mild and asymptomatic. Metronidazole, the only effective antiparasitic agent for trich.o.m.oniasis, has already been discussed (p. 30).

42.Antimicrobials during pregnancy Box 2.19 Pediculicides Lice infestation Mite infestations Lindane (Kwell, Scabene) Crotamiton (Eurax) Pyrethrins and piperonyl butoxide (RID, A- Lindane (Kwell, Scabene) 200).

Sulfur (6%) in petrolatum Pediculicides Both lice ( Pediculosis pubis Pediculosis pubis) and mite (scabies) infestations during pregnancy generally require some form of therapy. Several agents are available for treatment and are summarized in Box 2.19.

Of these, lindane (cream, lotion, or shampoo) is probably the most commonly used agent for both mites and lice. According to its manufacturer, lindane was not teratogenic in a variety of animals, although there are no adequate human reproduction studies.

Lindane may be related to an increase in stillbirths in some animal studies (Faber, 1996).

However, lindane may be absorbed systemically, which on rare occasions may lead to central nervous system toxicity (Feldman and Maibach, 1974; Orkin and Maibach, 1983). Although this adverse effect could also theoretically occur in the fetus, it would appear to be very unlikely and to date has not been reported. There is no information to suggest that any of the other agents listed in Box 2.19 cause adverse fetal effects, and thus all are apparently safe for use during pregnancy.

Antihelmintics Several antihelmintics are available to treated infested women, although it is usually not necessary to treat helminth infections during pregnancy. Both mebendazole (Vermox) and thiabendazole (Mintezol) are effective for a variety of helminths, including pinworms (enterobiasis), whipworm (trichuriasis), roundworm (ascariasis), and hookworm (uninariasis). According to their manufacturer, none of these drugs was teratogenic in laboratory animals, although there are no adequate human reproduction studies.

Pyrantel pomoate (Antiminth) is used primarily for the treatment of roundworm and pinworm. It may also be of use in treatment of whipworm infestations. Although this agent has not been shown to be teratogenic in animals, there are no adequate studies in humans.

Antimalarials The two major antimalarial drugs are chloroquine and quinine. Chloroquine is the primary drug used for the treatment of malaria, as well as for chemoprophylaxis in pregnant women who must travel to endemic areas (Diro and Beydoun, 1982). Although there have been no studies of infants whose mothers were treated for malaria during pregnancy with chloroquine, one study reported no increased frequency of congenital anomalies among 169 infants whose mothers received weekly low doses of the drug for malaria prophylaxis during pregnancy (Wolfe and Cordero, 1985). Quinine is used Special considerations Special considerations 43.primarily for chloroquine-resistant falc.i.p.arum malaria. Although there are no large studies regarding its use during pregnancy, increased malformations have been reported when large doses were used to attempt abortion (Nis.h.i.+mura and Tanimura, 1976).

Quinine sulfate tablets have also been utilized for leg cramps, but their efficacy is unproven. Although not recommended for the treatment of leg cramps during pregnancy, the antimalarial quinines should not be withheld in the seriously ill pregnant woman with chloroquine-resistant malaria.

Pyrimethamine, spiramycin, and sulfadiazine These agents are used primarily to treat toxoplasmosis. Pyrimethamine, a folic acid antagonist, is also used to treat malaria. There are no adequate scientific studies of its use during pregnancy, but Hengst (1972) reported no increase in the malformation rate in 64 newborns whose mothers had taken this drug during the first half of pregnancy.

Spiramycin has been used extensively in Europe during the first trimester with no apparent adverse fetal effects. Sulfadiazine, a sulfonamide, has not been reported to be teratogenic when used in the first trimester. However, as with all sulfonamides, it could potentially be related to hyperbilirubinemia in the newborn, especially in the premature infant.

SPECIAL CONSIDERATIONS.

There is a paucity of information regarding the most efficacious and safe antimicrobial regimens for the treatment of specific infection-related conditions during pregnancy (Table 2.3). The recommendations given in this section are derived from the author's experience or opinion.

Urinary tract infections Urinary tract infections are among the most common infections encountered in pregnant women (Duff, 1994). For example, asymptomatic bacteriuria occurs in 210 percent of all pregnant women (Whalley, 1967). The majority of these infections are caused by the Enterobacteriaceae or enteric group of organisms, with Escherichia coli Escherichia coli being the single most commonly isolated organism. Although it is often not necessary to treat these infections in nonpregnant women, it is of paramount importance to screen for and, if possible, eradicate bacteriuria in the pregnant woman, since acute pyelonephritis will develop in as many as 25 percent of untreated pregnant women with bacteriuria (Ka.s.s, 1978). being the single most commonly isolated organism. Although it is often not necessary to treat these infections in nonpregnant women, it is of paramount importance to screen for and, if possible, eradicate bacteriuria in the pregnant woman, since acute pyelonephritis will develop in as many as 25 percent of untreated pregnant women with bacteriuria (Ka.s.s, 1978).

The majority of pregnant women with asymptomatic bacteriuria can be treated successfully with a short course (35 days) of the antimicrobial regimens listed in Box 2.20.

An alternative regimen is to use nitrofurantoin macrocrystals, 100 mg given once a day at bedtime, for 710 days (Leveno et al et al., 1981). Single-dose regimens, as listed in Box 2.21, may also prove useful. Regardless of the antimicrobial regimen used, approximately two-thirds of the patients will be cured and remain bacteriuria-free for the remainder of the pregnancy; approximately one-third of the patients will experience a recurrence and require further therapy.

Symptomatic infection of the lower urinary tract (acute cyst.i.tis) can be treated with a variety of antimicrobial regimens similar to that used for asymptomatic bacteriuria, with 44 44 Antimicrobials during pregnancy Table 2.3 Summary of antimicrobial drugs: Teratogen Information System (TERIS) and Food and Drug Administration (FDA) risk estimates Summary of antimicrobial drugs: Teratogen Information System (TERIS) and Food and Drug Administration (FDA) risk estimates Drug TERIS risk FDA risk rating Acyclovir Topical: undetermined Bm Systemic: unlikely Amantadine Undetermined Cm Amoxicillin Unlikely Bm Amphotericin B Undetermined Bm Ampicillin None B.

Azithromycin Undetermined Bm Aztreonam Undetermined Bm Butoconazole Undetermined Cm Cefamandole Undetermined Bm Cefixime Undetermined Bm Chloramphenicol Unlikely C.

Chloroquine Daily therapeutic dose: minimal C.

Weekly prophylactic dose: none to minimal Ciclopirox Undetermined Bm Ciprofloxacin Unlikely Cm Clarithromycin Undetermined Cm Clindamycin Undetermined Bm Clotrimazole Unlikely B.

Erythromycin None Bm Famvir B.

Fluconazole Undetermined Cm Gentamicin Undetermined C.

Griseofulvin Undetermined C.

Idoxuridine Undetermined C.

Imipenem/cilastatin Undetermined Cm Ketoconazole Undetermined Cm Lindane Undetermined Bm Metronidazole None Bm Nitrofurantoin Unlikely Bm Norfloxacin Unlikely Cm Nystatin None Cm Penicillin None Bm Pyrazinamide Undetermined Cm Pyrimethamine Minimal Cm Quinine Very large doses: moderate D*

Low therapeutic doses: unlikely Ribavirin Undetermined Xm Spectinomycin Undetermined B.

Spiramycin Undetermined C.

Streptomycin Deafness: small Dm Malformations: none Sulfadiazine Unlikely NA.

Sulfamethoxazole Unlikely NA.

Terconazole Undetermined Cm Continued Special considerations 45.Table 2.3 Continued Continued Drug TERIS risk FDA risk rating Tetracycline Unlikely D.

Thalidomide High Xm Tolnaftate Undetermined NA.

Trimethoprim Minimal to small Cm Valacyclovir B.

Vancomycin Undetermined Bm Vidarabine Undetermined Cm Zidovudine Unlikely Cm NA, not available.

Compiled from: Friedman et al., Obstet Gynecol 1990; 75 75: 594; Briggs et al., 2005; Friedman and Polifka, 2006.

Box 2.20 Outpatient antimicrobial regimens for treatment of asymptomatic bacteriuria or cyst.i.tis during pregnancya asymptomatic bacteriuria or cyst.i.tis during pregnancya Ampicillin 250500 mg qid Ampicillin 250500 mg qid Nitrofurantoin 50100 mg qid Cephalosporins 250500 mg qid Sulfonamides 500 mg to 1 g qid aOral dose for 35 days.

Box 2.21 Single-dose antimicrobial regimens for the treatment of uncomplicated bacteriuria during pregnancy uncomplicated bacteriuria during pregnancy Amoxicillin 2 ga Nitrofurantoin 200 mg Ampicillin 2 ga Sulfisoxazole 2 Cephalexin 2 g aWith or without 1 g probenecid.

the exception that there is little information regarding the treatment of pregnant women with single-dose regimens, which are thus not recommended. These women can generally be treated as outpatients with an oral antimicrobial agent for 35 days (Box 2.20).

As with asymptomatic bacteriuria, recurrence in women with cyst.i.tis is common.

Therefore, it is important to have frequent surveillance cultures.

Symptomatic infection of the upper urinary tract or acute pyelonephritis is a relatively common complication occurring in approximately 1 percent of all pregnant women.

Many of these women experience nausea and vomiting, are dehydrated, and are unable to tolerate oral antimicrobial therapy. These women should be hospitalized for intravenous antibiotic therapy with one of the regimens listed in Box 2.22. As many as 25 percent of women with acute pyelonephritis during pregnancy will experience another such episode during either the antepartum or postpartum periods. Because of the attendant risks a.s.sociated with acute pyelonephritis during pregnancy, such as septic shock and premature labor, consideration should be given to continuous suppressive antimicrobial therapy following an initial episode of pyelonephritis. One particularly useful regimen is nitrofurantoin macrocrystals, 100 mg orally every night (Hankins and Whalley, 1985).

46.Antimicrobials during pregnancy Box 2.22 Inpatient antimicrobial regimens for the treatment of pregnant women with acute pyelonephritis pregnant women with acute pyelonephritis Ampicillin 500 mg IV q 6 h Piperacillin 34 g IV q 6 h Cefoxitin 12 g IV q 6 h Aminoglycoside plus antibiotic listed below: Cephalosporin (first generation) 500 mg IV q Gentamicin 3 mg/kg.day IV in divided doses 6 h Tobramycin 3 mg/kg.day IV in divided doses Mezlocillin 34 g IV q 6 h Cefazolin 12 g q 8 h is also useful.

Adapted from Duff, 1994.