Journal of Human Lactation http://jhl.sagepub.

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Use of Anti-Infective Agents During Lactation: Part 2Aminoglycosides, Macrolides, Quinolones,

Sulfonamides, Trimethoprim, Tetracyclines, Chloramphenicol, Clindamycin, and Metronidazole
Karen G. Chin, Charles E. McPherson III, Maria Hoffman, Ann Kuchta and Christina Mactal-Haaf
J Hum Lact 2001 17: 54
DOI: 10.1177/089033440101700111

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Chin et al.J Hum
J Hum LactLact 17(1),
17(1), 2001
2001Anti-Infective Agents

The Galactopharmacopedia

Use of Anti-Infective Agents During Lactation: Part 2Aminoglycosides,

Macrolides, Quinolones, Sulfonamides, Trimethoprim, Tetracyclines,
Chloramphenicol, Clindamycin, and Metronidazole
Karen G. Chin, PharmD, BCPS, Charles E. McPherson III, PharmD, Maria Hoffman, PharmD,
Ann Kuchta, PharmD, and Christina Mactal-Haaf, PharmD, BCPS

Abstract
Because many antibiotics are excreted into breast milk, it can be difficult for a practitioner to
choose an antibiotic for a lactating patient that will have minimal risks to her nursing infant.
This article is the second of a three-part series discussing the use of anti-infective agents dur-
ing lactation. The authors review general information regarding use and common side effects
for several classes of antibiotics. They also summarize information, including documented
milk concentrations, milk-to-plasma ratios, and other pharmacokinetic properties, in a table
that can help practitioners choose antibiotics that may be considered safe to use in the lactating
mother. J Hum Lact 2001;17(1):54-65.
Keywords: lactation, breastfeeding, human milk, anti-infectives

This article is the second of a three-part series discuss-
ing the use of anti-infective agents during lactation. We
have reviewed general information regarding usage and
common side effects for several classes of antibiotics.
We have also summarized information, including docu-
mented milk concentrations, milk-to-plasma ratios, and
other pharmacokinetic properties, in a table that can
help practitioners choose antibiotics that may be con-
sidered safe to use in the lactating mother (Table 1).
Please note that the table includes varying drug concen-
trations measured in breast milk based on the dose
administered, achievement of steady state, and the time
of sampling. Also note that the potential infant dosages
listed may vary widely based on the age and weight of
the infant and on the site and severity of the infection
Karen G. Chin, Charles E. McPherson III, Maria Hoffman, Ann
Kuchta, and Christina Mactal-Haaf are clinical assistant professors at the
University of Illinois at Chicago College of Pharmacy and pharmacothera-
pists in internal medicine at the University of Illinois at Chicago Hospital.
Address correspondence to Karen Chin, PharmD, BCPS, University of Illi-
nois at Chicago, Department of Pharmacy Practice, M/C 886, 833 S. Wood
Street, Room 164, Chicago, IL 60612, USA.
J Hum Lact 17(1), 2001
Copyright 2001 International Lactation Consultant Association
being treated. We have previously discussed some
physiologic and chemical factors that may affect the
1
excretion of medications into breast milk.
Aminoglycosides
Aminoglycosides are antibiotics used to treat infec-
tions caused by aerobic gram-negative bacteria, such as
Escherichia coli, Klebsiella oxytoca, and Pseudomonas
2
aeruginosa; staphylococci; and certain mycobacteria.
Aminoglycosides are commonly used to treat a variety
3
of infections in infants and children. Drugs within this
class include amikacin, gentamicin, kanamycin,
neomycin, netilmicin, streptomycin, and tobramycin.
These antibiotics have a polar structure, resulting in
negligible penetration across biological membranes and
2
poor oral absorption. Therefore, therapeutic serum lev-
els of aminoglycosides are achieved with parenteral
2
administration. Aminoglycosides are usually given in
combination with other antibiotics such as beta-lactams
2
to treat bacterial infections. Because of poor oral
absorption, some aminoglycosides are used for their
local effects on the gastrointestinal tract. For example,
kanamycin and neomycin are used in preoperative aero-

54

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J Hum Lact 17(1), 2001
2
bic gut sterilization. Tobramycin administered by inha-
lation is used in patients with cystic fibrosis to improve
2 8
pulmonary function. Systemic bioavailability of
inhaled tobramycin is low, with peak serum concentra-
tions of 0.95 to 1.05 mg/mL reported 1 hour after
4
tobramycin inhalation.
Gentamicin, tobramycin, and neomycin are also
available in ophthalmic dosage forms. Systemic side
effects have not been reported with ophthalmic
5
fixed-dose tobramycin-diclofenac use or with ocular
6
gentamicin topical administration. Neomycin is not
commercially available for parenteral administration.
The drug is administered orally as a solution or in tablets
or topically as a retention enema.
Significant adverse effects associated with therapeu-
tic aminoglycoside levels include nephrotoxicity,
2 12
ototoxicity, and rarely, neuromuscular block. Systemic
adverse reactions, which are similar to those reported in
3 7
adults treated with therapeutic aminoglycoside doses,
are unexpected in the nursing infant due to the fact that
aminoglycosides are secreted in breast milk in low con-
centrations and generally have poor oral absorption.
Macrolides
The macrolides have been widely used for infections
since the prototype erythromycin was introduced in
1952. Erythromycin is the drug of choice for
Mycoplasma pneumoniae infections, caused by
Legionella pneumoniae, Bordetella pertussis, and Chla-
mydia trachomatis. Other indications include pneumo-
nia caused by penicillin-sensitive streptococci includ-
ing Streptococcus pneumoniae and Staphylococcus
aureus. It is also useful against certain gram-negative
bacteria such as Neisseria meningitidis and gonor-
rhoea, Bordetella pertussis, Campylobacter jejuni, and
Moraxella catarrhalis. However, its activity against
Hemophilus influenzae is unreliable. It is a safer alterna-
tive to tetracycline for pregnant patients with
chlamydial pelvic infections and also an alternative to
7
penicillin G in patients allergic to the latter.
While erythromycin is safe and effective, the newer,
semisynthetic derivatives have the advantages of better
side-effect profiles, increased spectrum of activity, and
7
decreased risk for drug interactions. Clarithromycin
and azithromycin have increased activity against
Hemophilus influenzae and are effective in the treat-
ment and prophylaxis of Mycobacterium avium-
intracellulare. Clarithromycin is also used as part of a
number of combination regimens in the eradication of
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Anti-Infective Agents 55
Helicobacter pylori, an organism associated with peptic
7
ulcer disease. Roxithromycin displays no clear clinical
advantage over erythromycin. Troleandomycin, an
older agent, is marketed under an orphan drug status for
9
treatment of severe steroid-requiring asthma.
Clarithromycin, azithromycin, and roxithromycin
have increased stability in gastric acid and consequently
10,11
better absorption. Therefore, the nursing infant may
be able to absorb a larger percentage of these drugs.
Most adverse reactions with the macrolides,
erythromycin in particular, involve the gastrointestinal
tract, including nausea, vomiting, and diarrhea. Fewer
side effects of this nature are reported with clarithro-
mycin and azithromycin. Both drugs are extensively
distributed in body tissues with tissue concentration
greatly exceeding plasma levels. Azithromycin concen-
trates in tissues, particularly white blood cells, to such
an extent that a 5-day regimen can be given with efficacy
equal to that of a 7- to 10-day course of erythromycin.
Since the plasma concentration of azithromycin
12
declines rapidly over time after the last dose, the
amount of drug a nursing infant is exposed to should be
negligible. The nursing infant early in life can be
hypochlorhydric, which may result in increased absorp-
1
tion of weak bases such as macrolides.
Pyloric stenosis has been reported in infants treated
13,14
with erythromycin, and there is one case report of its
15
occurrence in a nursing infant. Topical erythromycin is
16
generally regarded as safe. However, gastrointestinal
motility was increased in neonates receiving
erythromycin ophthalmic ointment as prophylaxis
against chlamydial eye infections, indicating some
17
amount of systemic absorption.
Erythromycin and, to a lesser extent, clarithro-
18
mycin can inhibit the cytochrome-P450 metabolism of
multiple drugs, leading to potential toxicity in the nurs-
ing infant who may be receiving one of the interacting
drugs. Among those of possible significance in the
8 7
infant population are theophylline and caffeine, which
are used for neonatal apnea and other respiratory condi-
tions. Digoxin concentrations may increase due to an
inhibition of the digoxin-metabolizing bacteria in the
8
large bowel. In these instances, close monitoring of
signs and symptoms of toxicity as well as infant plasma
levels would be prudent. Human studies have shown no
7
major drug interactions with azithromycin.
The individual physical properties of each agent
must be taken into account when prescribing for the
nursing mother. Increased protein binding (clarithro-
56
mycin) and decreased oral absorption (dirithromycin,
azithromycin) would decrease the risk of absorption by
the nursing infant. The molecular weights as well as the
basic pH of most macrolides would favor passage into
breast milk (Table 1). However, in view of the low esti-
mated potential daily dose relative to the therapeutic
dose and benign side-effect profiles, maternal ingestion
of therapeutic doses of macrolides should not pose a
serious risk to most nursing infants.
Quinolones
The quinolones (nalidixic acid and cinoxacin) are
effective only for the genitourinary and gastrointestinal
tracts and have activity primarily against aerobic gram-
19
negative bacteria. The newer quinolones or the fluoro-
quinolones (ciprofloxacin, enoxacin, fleroxacin,
gatifloxacin, levofloxacin, lomefloxacin, moxifloxacin,
norfloxacin, ofloxacin, pefloxacin, sparfloxacin, and
trovafloxacin) have wider potential applications and a
19
broader spectrum of activity. The fluoroquinolones
are active against aerobic gram-positive cocci, gram-
negative bacilli, H. influenzae, M. catarrhalis, Legion-
20
ella species, M. pneumoniae, and C. pneumoniae.
Ofloxacin, levofloxacin, sparfloxacin, and trova-
floxacin show enhanced activity against S. pneumoniae
20
(including penicillin-resistant strains). Ciprofloxacin
remains the most potent agent against P. aeruginosa but
19
is not active against S. aureus and S. pneumoniae.
20
Trovafloxacin is the most active against anaerobes.
The fluoroquinolones (except norfloxacin) penetrate
most tissues well, especially bronchial mucosa, lung,
19
gallbladder, kidney, prostate, genital tract, and bone.
The fluoroquinolones are generally well tolerated,
with gastrointestinal upset occurring in approximately
19
5% of patients. Other adverse effects are allergic reac-
tions and photosensitivity, particularly with lome-
19
floxacin and sparfloxacin. Trovafloxacin has recently
been found to be associated with rare but fatal cases of
19
liver toxicity. Sparfloxacin prolongs the QT interval in
the electrocardiogram in approximately 3% of patients,
and there have been rare cases of cardiac arrhythmias
19
(i.e., Torsades de pointe).
The fluoroquinolones possess good oral bioavailability
(except norfloxacin), low protein binding, and good tis-
sue penetration (except norfloxacin), which enhances
21
the likelihood of their passage into breast milk. The
topical formulations of ciprofloxacin, norfloxacin, and
ofloxacin have been shown to have minimal systemic
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Chin et al. J Hum Lact 17(1), 2001
absorption (Alcon, Merck, and Allergan, personal com-
munications, September 2000).
The use of fluoroquinolones in children has been lim-
ited because of the potential to induce arthropathy in
juvenile animals, which has resulted in a moratorium
22
against their use in children. Therefore, the use of
fluoroquinolones is contraindicated in children, grow-
22
ing adolescents, and pregnant and lactating women.
Nevertheless, fairly extensive compassionate use of
ciprofloxacin and other fluoroquinolones (norfloxacin
and pefloxacin) have shown that prolonged use is well
tolerated in pediatric patients and that there has been no
23
significant evidence of chondrotoxicity in this group.
During the past 10 years, fluoroquinolones have been
used in pediatric patients in circumstances where they
were the only antibacterial agents active in infections
caused by multiresistant organisms. These included
children with cystic fibrosis, complicated urinary tract
infections, enteric infections (in developing countries),
22
and chronic ear infections.
Sulfonamides and Trimethoprim
Sulfonamides are a class of antibiotics that are used
primarily for the treatment of infections caused by
gram-positive and gram-negative aerobic bacteria.
These agents are commercially available in many differ-
ent dosage forms, including topical, ophthalmic, oral,
and parenteral formulations. Major side effects associ-
ated with sulfonamide use include gastrointestinal
intolerance, hypersensitivity, rash, bone marrow sup-
24
pression, and megaloblastic anemia.
Controversy surrounds the use of sulfonamides dur-
ing the neonatal period. In general, most of these drugs
are highly bound to serum albumin. The affinity of sul-
fonamides for albumin varies greatly; some are more
tightly bound than others. Consequently, these drugs
compete for albumin binding sites with bilirubin, in
25
addition to displacing bilirubin. Increased free, circu-
lating bilirubin in the neonate can readily cross the
blood-brain barrier and potentially deposit in the brain,
resulting in a condition known as kernicterus.26 For this
reason, systemic use of these drugs is avoided in prema-
ture infants and newborns younger than 2 months of
age. Also, there is a risk of hemolytic anemia in infants
who are glucose-6-phosphate-dehydrogenase
27
(G-6-PD) deficient.
Knowing the pharmacokinetic properties of sulfona-
mides can assist in making rational decisions about the
J Hum Lact 17(1), 2001
use of these agents in nursing mothers. These agents are,
for the most part, lipophilic and passively diffuse across
biologic membranes and, therefore, into breast milk.
Sulfisoxazole, however, is one of the most water soluble
of the sulfonamides and does not cross into breast milk
25
readily. The degree of protein binding also affects the
amount of drug that can transfer into breast milk, as only
unbound or free drug will cross. Extensive protein bind-
ing of sulfonamides limits the amount of free drug that
can cross into breast milk, which explains why sulfona-
mides are excreted in breast milk in low concentrations
(Table 1).
Oral absorption of sulfonamides in the infant is
another property that must be assessed when determin-
ing whether or not these drugs should be used in a nurs-
ing mother. These agents are readily absorbed from the
28
small intestine. Only sulfasalazine is poorly absorbed,
with only 10% to 15% of a dose reaching the plasma as
28
unchanged drug. Protein binding of sulfonamides is
28
variable, ranging from 32% to 90%. However, it is the
ability of these agents to displace bilirubin from serum
proteins that is of greatest concern. While all sulfona-
mides displace bilirubin from albumin-binding sites,
26
they do so to varying degrees. Sulfasalazine has the
greatest bilirubin-displacing ability. However, since this
drug is poorly absorbed from the gastrointestinal tract,
low maternal blood concentrations are achieved with
standard adult doses. The resultant concentration in
breast milk is not high enough to cause bilirubin dis-
26
placement upon ingestion by the nursing newborn.
Furthermore, sulfapyridine, the active metabolite of
26
sulfasalazine, has minimal displacing ability.
Sulfisoxazole (sulphafurazole) can also markedly dis-
place bilirubin from albumin.26 Bilirubin displacement
does not usually occur when infant sulfisoxazole serum
25
drug concentrations are less than 50 mcg/mL. This is
greater than the predicted serum sulfizoxazole concen-
trations in nursing infants absorbing sulfisoxazole-con-
taining breast milk.25 Of all the sulfonamides, however,
sulfadiazine and sulphanilamide are least likely to dis-
26
place bilirubin. Although specific human data regard-
ing sulfamethoxazole and breastfeeding are limited,
therapeutic concentrations of sulfamethoxazole and
trimethoprim (co-trimoxazole) in neonates do not
appear to displace bilirubin from albumin-binding
29
sites. There are no published accounts of adverse
effects in the nursing infant associated with maternal
use of topical or ophthalmic sulfonamide preparations.
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Anti-Infective Agents 57
Because of the pharmacokinetic properties of sul-
fonamides, little drug actually passes into breast milk.
Thus, adverse effects associated with their use in the
nursing infant have been minimal (Table 1). There is a
case report of bloody diarrhea in an infant whose mother
30
was receiving therapeutic doses of sulfasalazine. In
general, maternal sulfonamide use is considered safe
while breastfeeding healthy newborns. However, cau-
tion should be used in critically ill, preterm, G-6-PD
31
deficient, or hyperbilirubinemic neonates.
Trimethoprim is an oral or parenteral antibiotic that is
oftentimes used in combination with sulfonamides,
such as sulfamethoxazole. Although trimethoprim
passes into breast milk in low concentrations, no
31
adverse effects have been reported with its use. The
American Academy of Pediatrics considers trimetho-
prim, in combination with sulfamethoxazole, to be com-
patible with breastfeeding.32 Therapeutic concentrations
of trimethoprim, however, have been associated with
4
megaloblastic anemia and bone marrow suppression.
Tetracyclines
The class of antibiotics known as the tetracyclines
has been in clinical use since the 1940s. Although they
have activity against a variety of gram-positive and
gram-negative bacteria, tetracyclines are commonly
used to treat infections caused by atypical organisms,
such as mycoplasma and rickettsia, and sexually trans-
mitted diseases, including chlamydia and syphilis.
33
There are currently six agents that are commercially
available, and each is classified according to its duration
of action. Tetracycline and oxytetracycline are
short-acting, methacycline and demeclocycline are
intermediate-acting, and doxycycline and minocycline
are long-acting agents.
Common side effects associated with the use of
tetracyclines include gastrointestinal intolerance,
photosensitivity, dental staining, hepato-toxicity and
34
nephro-toxicity. One important fact about
tetracyclines is that they have an increased affinity for
divalent cations, such as calcium. For this reason, these
agents should not be used within 2 hours of administra-
tion of dairy products, antacids, or iron products
because decreased oral absorption of the antibiotic may
4
occur. Tetracyclines are contraindicated for use during
pregnancy and in children younger than 8 years of age,
as they have been associated with reduced bone growth
27
and permanent tooth discoloration. Generally speak-
58
ing, because these drugs bind to calcium in maternal
breast milk, there is little concern for oral absorption in
31
the nursing infant. Doxycycline and minocycline,
however, have a decreased affinity for calcium com-
pared to the older tetracyclines and, therefore, have an
21
increased likelihood for oral absorption. Though they
are not contraindicated for use during breastfeeding, tet-
racycline use generally is not recommended, as there
exist other classes of antibiotics with similar spectrums
of activity that have a better safety profile.
Miscellaneous
Chloramphenicol
Chloramphenicol possesses a broad spectrum of
activity against most aerobic and anaerobic bacteria. It
also possesses activity against rickettsia, chlamydia,
35
mycoplasma, and spirochetes. Chloramphenicol is
available in several formulations, including oral cap-
sules, an oral suspension, a parenteral preparation, and
topical agents for ophthalmic and otic use. Both the oral
suspension and the parenteral preparation require
hydrolysis in order to be activated. Malnourished chil-
dren and neonates may be unable to hydrolyze the drug
and thus be unable to achieve therapeutic serum
35
chloramphenicol concentrations. Unlike the systemic
formulations, ophthalmic preparations of chloram-
phenicol do not provide measurable systemic drug con-
36,37
centrations. Chloramphenicol is highly lipid soluble
and distributes well in most body fluids, including the
35
central nervous system and breast milk (Table 1).
Despite its broad spectrum of activity, the therapeutic
use of chloramphenicol has fallen out of favor due to its
side-effect profile. Chloramphenicol has been associ-
ated with a 13-fold increase in the risk of aplastic ane-
mia that is generally fatal and does not appear to be dose
35
related. Bone marrow suppression (anemia,
leukopenia, and/or thrombocytopenia), optic neuritis,
peripheral neuropathy, headache, confusion, and gas-
35
trointestinal complaints may also occur. Despite the
observation that ophthalmic preparations do not achieve
measurable systemic drug concentrations, reports exist
of bone marrow suppression following the use of oph-
36,37
thalmic preparations. Because of these reports, it is
reasonable to use caution when prescribing topical
chloramphenicol products to patients with other predis-
posing factors for blood dyscrasias (i.e., personal or
family history of blood dyscrasias, concomitant use of
other marrow-suppressive medications). There are no
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Chin et al. J Hum Lact 17(1), 2001
published reports of breastfeeding mothers who have
received ophthalmic chloramphenicol; thus, the effect
of these preparations on the nursing infant is unclear.
Gray baby syndrome, which primarily affects neo-
nates, has also been associated with the therapeutic use
of chloramphenicol in infants. Symptoms include
abdominal distention, vomiting, cyanosis, irregular res-
piration, flaccidity, and circulatory collapse. Gray baby
syndrome is dose related, generally occurs with serum
chloramphenicol levels higher than 50 mcg/ml, and is
35
potentially fatal.
Chloramphenicol may also reduce vitamin K synthe-
sis, leading to coagulation disorders. It may also inhibit
the metabolism of some drugs that are metabolized via
the cytochrome P-450 system such as phenytoin and
warfarin. In addition, drugs that induce the cytochrome
P-450 system, such as phenobarbital, phenytoin, and
rifampin, may decrease serum chloramphenicol con-
centrations. Chloramphenicol should not be used in
combination with clindamycin since these agents com-
petitively inhibit each other.35
While the drug is not contraindicated in breastfeed-
ing, the American Academy of Pediatrics suggests cau-
tion when prescribing chloramphenicol to breastfeed-
32
ing mothers. Based on the drugs potential to cause
potentially life-threatening side effects as well as its
ability to cross into breast milk, anti-infective therapy
with systemic chloramphenicol should be reserved for
patients with severe infections or those who cannot tol-
erate or have failed therapy with other anti-infective
agents. Recommendations for the use of topical
chloramphenicol are less clear however, as previously
mentioned; the practitioner may choose to avoid its use
in lactating mothers with risk factors for blood
dyscrasias.
Clindamycin
Clindamycin is active against most anaerobic organ-
isms as well as most gram-positive aerobic organisms
with the exceptions of Enterococcus and methicillin-
resistant S. Aureus. It has negligible activity against
35
gram-negative aerobic organisms. Clindamycin also
possesses some antiparasitic activity and has been used
in conjunction with other agents for the prophylaxis and
38
treatment of toxoplasmosis and pneumocystis carinii.
Topical preparations of clindamycin are often used in
the treatment of dermatologic disorders such as acne
vulgaris and rosacea. Intravaginal clindamycin is used
35
for the treatment of bacterial vaginosis. Clindamycin
J Hum Lact 17(1), 2001
has rapid and near complete absorption following oral
35
administration. In contrast, 1.7% to 7.5% of the dose
of topical clindamycin may be systemically absorbed
39,40
depending on the vehicle used. An average of 4%
(range 2.7-4.7%) of a 100-mg dose is systemically
absorbed following the administration of clindamycin
41
intravaginal cream. Clindamycin should not be used in
combination with macrolide antibiotics or chloram-
phenicol because these agents competitively inhibit
35
each other.
Common side effects of clindamycin include nausea,
vomiting, flatulence, and diarrhea. The incidence of
clindamycin-induced C. difficile colitis with associated
35
diarrhea has been reported from 0.01% to 10%. While
C. difficile colitis is often mild and self-limiting, it can
be a potentially life-threatening reaction. Other reac-
tions can include increased liver function tests and
35
hypersensitivity reactions. Though rare, reports of
42
diarrhea following use of topical clindamycin exist.
There are no published reports regarding the use of topi-
cal clindamycin in breastfeeding mothers; thus, the
effect of the drug on the nursing infant is unclear.
Although clindamycin does cross into breast milk
(Table 1), the American Academy of Pediatrics consid-
ers clindamycin a safe anti-infective agent to use in the
32
lactating mother.
Metronidazole
Metronidazole is active against most gram-negative
anaerobic and some gram-positive anaerobic organ-
isms. It also possesses activity against H. pylori and
some protozoa. Most aerobic organisms are resistant to
35
metronidazole. Topical preparations of metronidazole
can be used for the treatment of acne rosacea.
Intravaginal metronidazole is used for the treatment of
35
bacterial vaginosis. Metronidazole has rapid and
near-complete oral absorption and penetrates well into
35
all tissues, including the central nervous system. In
contrast, an average of 56% of a 37.5-mg dose is sys-
temically absorbed following intravaginal gel adminis-
43
tration, whereas an average of 19% of the dose of intra-
44
vaginal tablets may be absorbed. Metronidazole also
appears to cross readily into breast milk following sys-
temic administration to the lactating mother (Table 1).
Common side effects of metronidazole include nau-
sea, diarrhea, dry mouth, stomatitis, and metallic taste.
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Anti-Infective Agents 59
It has also been associated with the disulfiram reaction
when taken concomitantly with alcohol. This reaction
may be of concern if the nursing infant is prescribed
medications that are solubilized with alcohol (i.e., phe-
nobarbital, theophylline elixir). Other severe though
less common side effects include seizures, cerebellar
35
dysfunction, and peripheral neuropathy. Since
high-dose metronidazole has been associated with
tumorigenic effects in mice and rats, concerns exist for
35
its carcinogenic and mutagenic potential in humans.
Thus far, there is no documented evidence that
metronidazole possesses carcinogenic effects in
humans. Metronidazole may also inhibit the metabo-
lism of certain drugs metabolized via the cytochrome
35
P-450 pathway, such as warfarin. However, these
drugs are generally not administered in the neonatal and
infancy periods.
Based on the concerns for carcinogenic potential in
humans, the American Academy of Pediatrics suggests
caution regarding the therapeutic use of systemic
metronidazole in lactating mothers, including the tem-
32
porary cessation of breastfeeding ( Table 1). There is
no documented evidence to either support or oppose the
use of topical or intravaginal metronidazole therapy in
the nursing mother. However, as intravaginal
metronidazole does have limited systemic absorption, it
is possible for the nursing infant to ingest a small
amount of the drug that crosses into the breast milk.
References
1. Chin KG, Mactal-Haaf C, McPherson CE III. Use of anti-infective agents
during lactation: Part 1beta-lactam antibiotics, vancomycin,
quinupristin-dalfopristin, and linezolid. J Hum Lact. 2000;16:351-358.
2. Edson RS, Terrell CL. Symposium on antimicrobial agentsPart VIII:
the aminoglycosides. Mayo Clin Proc. 1999;74:519-528.
3. Henry NK, Hoecker JL, Rhodes KH. Antimicrobial therapy for infants
and children: guidelines for the inpatient and outpatient practice of pedi-
atric infectious diseases. Mayo Clin Proc. 2000;75:86-97.
4. Takemoto CK, Hodding JH, Kraus DM. Pediatric Dosage Handbook. 6th
ed. Cleveland, Ohio: Lexi-Comp; 1999.
5. Salva P, Costa J, Andreu D, Notivol R, Martinez M. Tolerability and
safety of 0.1% diclofenac plus 0.3% tobramycin fixed-dose ophthalmic
solution: a randomized, comparative, controlled study in healthy volun-
teers. Methods Find Exp Clin Pharmacol. 1999;21:203-208.
6. Trope GE, Lawrence JR, Hind VM, Everden A. Systemic absorption of
topical and subconjunctival gentamicin. Br J Ophthalmol. 1979;
63:692-693.
7. Alvarez-Elcoro S, Enzler MJ. Symposium on antimicrobial agentspart
IX: the macrolides: erythromycin, clarithromycin and azithromycin.
Mayo Clin Proc. 1999;74:613-634.
 60
Table 1. Anti-Infective Agents and Their Effect on Lactation.
American
Potential Therapeutic Academy of
Milk Milk-to- Infant Infant Pediatrics
Generic Name Dosage Concentrations Plasma Dose Dose (AAP)
Antibiotic Class (brand name) Forms* (mcg/ml) Ratio (mg/kg/d) **
(mg/kg/d) Compatible

Special Considerations

General concerns for infant ingestion include potential for allergic re-
action, changes in bowel flora, and confounding of culture results by
the ingested antibiotic if a fever workup is done in the nursing
infant.
2
Aminoglycosides All aminoglycosides have negligible protein binding.
21,31
Amikacin (Amikin) P Trace Unknown Unknown 1522.5 NR Concentration during 6 h following 100- and 200-mg IM doses in 2 of
21,31
4 patients.
Downloaded from jhl.sagepub.com at BROWN UNIVERSITY on December 12, 2012

Gentamicin Op, Ot, P 0.41-0.4945 0.11-0.4421,31 0.074 7.50 NR Two bloody stools were reported in a breastfed infant; the nursing
(Garamycin) mother was on clindamycin and gentamicin. Causal relationship is
unknown.46
Kanamycin (Kantrex) O, P 18.447 0.05-0.4048 2.76 1549 Y Milk concentration following a 1-g IM dose.47
Neomycin O, Op, Ot, T Unknown Unknown Unknown 50 NR
(Neo-Fradin)
Netilmicin P Unknown Unknown Unknown NR
(Netromycin)
50
Streptomycin P 0.3-0.6 0.12-1.0 21,31 0.09 10-20 Y
21,31
Tobramycin (Nebsin) I, Op, P 0.52 Unknown 0.08 7.5 NR
Macrolides
51 51
Azithromycin O, P 0.64-2.8 Unknown 0.42 15-50 (in- NR 37% oral absorption. Protein binding is concentration dependent,
11
(Zithromax) fant age > decreasing with increasing concentration (15-50%).
6 mo)
Clarithromycin O Unknown Unknown Unknown 15 (infant NR MW 748.0, 50% oral absorption.52 72% protein binding, which de-
53
(Biaxin) age > 6 creases with increasing concentration.
mo)
Dirithromycin O Unknown Unknown Unknown Efficacy and NR MW 835, 6-14% bioavailable, protein binding 15-30%.55 Excreted in
54
(Dynabac) safety not milk of lactating rodents.
established
in patients
< 12
years.54
56,57 56,57 58
Erythromycin (various) O, Op, P, T 0.4-3.2 0.51.3 0.06-0.48 15-50 Y Diarrhea and irritability have been reported in nursing infants. Py-
15
loric stenosis has been reported in one breastfed infant.
59 60 11
Roxithromycin O Unknown 0.04 0.06 5-10 NR MW 837. Protein binding is also concentration dependent (80-96%).
(Assoral) Less than 0.05% of a 300 mg dose is excreted in breast milk over
59
12 h.
 || || 9
Troleandomycin (TAO) O, P 0.38 0.5 0.057 3.5-14 NR
Quinolones
Cinoxacin (Cinobac) O Unknown Unknown Unknown Unknown NR
61 61 61
Ciprofloxacin (Cipro, O, Op, Ot, P 0.98 4.67 0.147 7-40 NR Infant serum concentration was below assay limit (< 0.03 mcg/ml),
Ciloxan, Cipro HC but infant was breastfed 8 hours after single daily dose of
Otic) ciprofloxacin.61 Mother recovering from acute renal failure and had
received a single dose of ciprofloxacin; infant not allowed to breast-
feed.62 Case report of perforated pseudomembranous colitis in a
64
breastfed infant whose mother self-administered ciprofloxacin.
1.98-3.062 1.7 (mean)62 0.4562
63 61 63
0.02-3.79 0.85-2.14 0.57
Enoxacin (Penetrex) O Unknown Unknown Unknown Unknown NR
65
Fleroxacin (Megalocin, O, P 3.5 (mean) 0.625 0.525 Unknown NR Not commercially available in the US.
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65 65
Quinodis, others) (mean) (mean)
Gatifloxacin (Tequin) O, P Unknown Unknown Unknown Unknown NR
Levofloxacin O, P (see (see (see Unknown NR Levofloxacin is the optical isomer of ofloxacin, and its passage into
(Levaquin) ofloxacin ofloxacin ofloxacin milk should be similar; the milk concentrations of ofloxacin are sim-
31
data) data) data) ilar to those in serum.
Lomefloxacin O Unknown Unknown Unknown Unknown NR
(Maxaquin)
Moxifloxacin (Avelox) O Unknown Unknown Unknown Unknown NR
21 21 21 4 67
Nalidixic Acid O 5 0.08-0.13 0.75 55 Y Single case report of hemolytic anemia in an infant. Retrospective
(Negram) review of 63 women treated with nalidixic acid during pregnancy,
and none of the infants developed congenital deformity of
intracranial hypertension.68
0.3-1.166 0.06166 0.16566
Norfloxacin (Noroxin, O, Op Unknown Unknown Unknown Unknown NR Limited data available regarding secretion into breast milk, but it has
69
Chibroxin) been suggested that it is not secreted into breast milk. Package in-
70
sert states 200-mg dose not detectable in breast milk. Widely used
71
in the pediatric patient population in Japan.
63 63 63
Ofloxacin (Floxin, O, Op, Ot, P 0.05-2.41 0.98-1.66 0.36 Unknown NR
Ocuflox, Oculfox
Otic)
63
Pefloxacin (Abaktal, O, P 0.88-3.54 0.74-163 0.53163 PO: 12 mg NR Not commercially available in the US. Several case reports of
Azuben, others) (for salmo- pefloxacin-induced arthropathy in children.73,74,75
nella)72;
IV: 400mg
Q12H (for
meningitis
in children
6 mo to 12
yr)72
61

(continued)
 62
Table 1 Continued
American
Potential Therapeutic Academy of
Milk Milk-to- Infant Infant Pediatrics
Generic Name Dosage Concentrations Plasma Dose Dose (AAP)
Antibiotic Class (brand name) Forms* (mcg/ml) Ratio (mg/kg/d)** (mg/kg/d) Compatible Special Considerations

Sparfloxacin (Zagam) O Unknown Unknown Unknown Unknown NR

Trovafloxacin/Alatro- O, P Unknown Unknown Unknown Unknown NR Alatrofloxacin is the intravenous formulation that is metabolized to
floxacin (Trovan) trovafloxacin.
Sulfonamides and
Trimethoprim
Sulfabenzamide T Unknown Unknown Unknown Unknown NR
Sulfacetamide O, Op, T Unknown Unknown Unknown Unknown NR
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(Sulamyd and others)

21
Sulfadiazine (Silvadene O, T Unknown Unknown Unknown 100 NR Absorption is complete after oral administration ; 32-56% protein
28
and others) binding.
28
Sulfamethizole O Unknown Unknown Unknown Unknown NR Readily absorbed after oral administration; 90% protein binding.
(Thiosulfil forte)
Sulfamethoxazole O Unknown 0.0621 Unknown 50-75 Y (in com- 50-70% protein bound.28
(Gantanol, Urobak) bination
with
trimetho-
prim)
Sulfanilamide (Vagitrol T Unknown Unknown Unknown Unknown NR
and others)
76,77 77
Sulfapyridine O 10.3 0.5 1.54 Y
21 21
Sulfasalazine O 0.5-2 0.09-0.17 0.3 Contraindi- Y 10-15% oral absorption as unchanged drug. Poor bilirubin displacing
(Azulfidine) cated in ability; one episode of bloody diarrhea reported in the nursing infant
children < of a mother who was a slow acetylator.30
2 yrs
Sulfathiazole O, T Unknown unknown unknown unknown NR
25 28
Sulfisoxazole (Gantri- O, Op 0.45% of 0.06 Unknown 120-150 in Y Readily absorbed; 88% protein bound.
sin) maternal infants 2
dose found mos
in breast
25
milk
21 21 58
Trimethoprim O 2 1.25 0.3 4-6 Y (in com- Co-trimoxazole: poor feeding has been reported in nursing infants.
(Proloprim, Trimpex) bination
with
sulfameth-
oxazole)
 4
Tetracyclines Tetracyclines are contraindicated for oral use in children < 8 yrs.
Demeclocycline O Unknown Unknown Unknown Unknown NR
(Declomycin)
21 31
Doxycycline O, P 0.38-0.77 0.3-0.4 0.115 Unknown NR
(Vibramycin and oth-
ers)
Methacycline Unknown Unknown Unknown Unknown NR
Minocycline (Minocin, O, P Unknown Unknown Unknown Unknown NR
Dynacin)
Oxytetracycline (Terra- O, P Unknown Unknown Unknown Unknown NR
mycin and others)
21 21
Tetracycline (Sumycin O, Op, T 0.43-2.58 0.6-0.8 0.39 Unknown Y
and others)
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Miscellaneous
77
Chloramphenicol O, Op, Ot, P, 16-25 0.51-0.6277 3.75 20-100 U Refusal of the breast, somnolence during feeding, gas, and
(Chloromycetin and T postfeeding emesis has been reported in nursing infants.31 Lactating
others) mothers received multiple doses of chloramphenicol in references
77 and 78 versus single-dose therapy in reference 57.
78
0.54-6.10 NA
57
trace-4.2
79 79 46
Clindamycin (Cleocin O, P, T, V < 0.5-3.1 0.08-3.1 0.570 10-40 Y Bloody stools in a nursing infant has occurred. Lactating mothers
and others) received multiple doses of clindamycin in references 79 and 80 ver-
sus single dose therapy in reference 57.
80
0.74-3.8 NA
57
trace-1.2
Metronidazole (Flagyl O, P, T, V 3.5-45.881 NA 6.87 7.5-50 U Loose stools, feeding problems, and candidiasis have been reported in
82
and others) nursing infants. One report of diarrhea and secondary lactose intol-
83
erance in a nursing infant exists. Lactating mothers received multi-
ple doses of metronidazole in reference 82 versus single-dose ther-
apy in reference 81.
82 82
8.99-15.52 0.88-0.96

* I = inhalation, O = oral, Op = ophthalmic, Ot = otic, P = parenteral, T = topical, V = vaginal.

** Calculated by multiplying maximum known concentration achieved in breast milk by average milk intake (150 ml/kg/day).
Obtained from reference 4, unless otherwise specified.
Obtained from reference 32: Y = yes, NR = not reviewed, U = effect in nursing infants unknown but may be of concern.
Percentage oral absorption and percentage protein binding noted in adult patients.
|| Pfizer, personal communication, October 2000.
AAP suggests cessation of breastfeeding for 12-24 h after single-dose therapy is given to the mother to allow for clearance of the drug.
63
64
8. Guay RP. Macrolide antibiotics in paediatric infectious diseases. Drugs.
1996;4:515-536.
9. Eitches RW, Rachelefsky GS, Katz RM, Mendoza GR, Siegel SC.
Methylprednisolone and troleandomycin in treatment of steroid-depend-
ent asthmatic children. AJDC. 1985;139:264-268.
10. Klein JO. History of macrolide use in pediatrics. Pediatr Infect Dis J.
1997;16:427-431.
11. Nilsen OG. Pharmacokinetics of macrolides: Comparison of plasma, tis-
sue and free concentrations with special reference to roxithromycin. In-
fection. 1995;(suppl)1:5-9.
12. Amsden GW, Nafziger AN, Foulds G. Pharmacokinetics in serum and
leukocyte exposures of oral azithromycin, 1,500 milligrams given over a
3- or 5-day period in healthy subjects. Antimicrob Agents Chemother.
1999;43:163-165.
13. Honein MA, Paulozzi LJ, Himelright IM, et al. Infantile hypertrophic py-
loric stenosis after pertussis prophylaxis with erythromycin: a case re-
view and cohort study. Lancet. 1999;354:2101-2105.
14. SanFilippo JA. Infantile hypertrophic pyloric stenosis related to ingestion
of erythromycin estolate: a report of five cases. J Ped Surg. 1976;
11:177-179.
15. Stang H. Pyloric stenosis associated with erythromycin ingested through
breast milk. Minn Med. 1986;69:669-682.
16. Rothman KF, Pochi PE. Use of oral and topical agents for acne in preg-
nancy. J Am Acad Dermatol. 1988;3:431-442.
17. Moussa F, Alaswad B, Gardia J. Erythromycin eye ointment: effect on
gastroinstestinal motility. Am J Gastroenterol. 2000;3:826.
18. Fraschini F, Scaglione F, Demartini G. Clarithromycin clinical
pharmacokinetics. Clin Pharmacokinet. 1993;3:189-204.
19. Walker RC. The fluoroquinolones: symposium on antimicrobial
agentspart XIII. Mayo Clin Proc. 1999;74:1030-1037.
20. Bartlett JG, Breiman RF, Mandell LA, File TM. Guidelines from the In-
fectious Diseases Society of America. Clin Infect Dis. 1998;26:818-838.
21. Hale T. Medications and Mothers Milk. 8th ed. Amarillo, Tex:
Pharmasoft Medical Publishing; 1999.
22. Schaad UB. Pediatric use of quinolones. Ped Infect Dis J.
1999;18:467-470.
23. Ball P, Mandell L, Niki Y, Tillotson G. Comparative tolerability of the
newer fluoroquinolone antibacterials. Drug Safety. 1999;21:407-421.
24. Kucers A, Crowe SM, Grayson ML, Hoy JF: Sulfonamides. In Kucers A,
et al., eds. The Use of Antibiotics: A Clinical Review of Antibacterial,
Antifungal, and Antiviral Drugs. Oxford, UK: Butterworth-Heinemann;
1997:805-835.
25. Kauffman RE, OBrien C, Gilford P. Sulfisoxazole secretion into human
milk. J Pediatr. 1980;97:839-841.
26. Walker PC. Neonatal bilirubin toxicity: a review of kernicterus and the
implications of bilirubin displacement. Clin Pharmacokin. 1987;
13:26-50.
27. Dillon AE, Wagner CL, Wiest D, Newman RB. Drug therapy in the nurs-
ing mother. Obstet Gynecol Clin. 1997;24:675-697.
28. Sulfonamides. In AHFS Drug Information. Bethesda, Md: American So-
ciety of Health-System Pharmacists; 2000:755-766.
29. Springer C, Eyal F, Michel J. Pharmacology of trimethroprim-
sulfamethaxazole in newborn infants. J Pediatr. 1982;100:647-649.
30. Branski D, Kerem E, Gross-Kieselstein E, Hurvitz H, Litt R, Abrahamov
A. Bloody diarrheaa possible complication of sulfasalazine trans-
ferred through human breast milk. J Pediatr Gastroenterol Nutr.
1986;5:316-317.
31. Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation.
5th ed. Baltimore, Md: Williams & Wilkins; 1998.
32. American Academy of Pediatrics Committee on Drugs. Transfer of drugs
and other chemicals into human milk. Pediatrics. 1994;93:137-150.
33. Kucers A, Crowe SM, Grayson ML, Hoy JF: Tetracyclines. In Kucers A,
et al., eds. The Use of Antibiotics: A Clinical Review of Antibacterial,
Downloaded from jhl.sagepub.com at BROWN UNIVERSITY on December 12, 2012
Chin et al. J Hum Lact 17(1), 2001
Antifungal, and Antiviral Drugs. Oxford, UK: Butterworth-Heinemann;
1997:719-762.
34. American Academy of Pediatrics Committee on Drugs. Requiem for
tetracyclines. Pediatrics. 1975;55:142-143.
35. Kasten MJ. Symposium on antimicrobial agentspart XI: clindamycin,
metronidazole, and chloramphenicol. Mayo Clin Proc. 1999;74:825-833.
36. Trope GE, Lawrence JR, Hind VMD, Bunney J. Systemic absorption of
topically applied chloramphenicol eyedrops. Br J Ophthalmol.
1979;63:690-691.
37. Walker S, Diaper CJM, Bowman R, Sweeney G, Seal DV, Kirkness CM.
Lack of evidence for systemic toxicity following topical chloram-
phenicol use. Eye. 1998;12:875-879.
38. Fletcher C, Kakuda TN, Collier AC. Human immunodeficiency virus
infection. In DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BR,
Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 4th
ed. Stamford, Conn: Appleton and Lange; 1999:1930-1956.
39. Eller MG, Smith RB, Phillips JP. Absorption kinetics of topical
clindamycin preparations. Biopharm Drug Dispos. 1989;10:505-512.
40. Barza M, Goldstein JA, Kane A, Feingold DS, Pochi PE. Systemic ab-
sorption of clindamycin hydrochloride after topical application. J Am
Acad Dermatol. 1982;7:208-214.
41. Borin MT, Powley GW, Tackwell KR, Batts DH. Absorption of
clindamycin after intravaginal application of clindamycin phosphate 2%
cream. J Antimicrob Chemother. 1995;35:833-841.
42. Voron DA. Systemic absorption of topical clindamycin. Arch Dermatol.
1978;114:798.
43. Cunningham FE, Kraus DM, Brubaker L, Fischer JH. Pharmacokinetics
of intravaginal metronidazole gel. J Clin Pharmacol. 1994;
34:1060-1065.
44. Fredricsson B, Hagstrom B, Nord C, Rane A. Systemic concentrations of
metronidazole and its main metabolites after intravenous, oral and vagi-
nal administration. Gynecol Obstet Invest. 1987;24:200-207.
45. Celiloglu M, Celiker S, Guven H, Tuncok Y, Demir N, Erten O.
Gentamicin excretion and uptake from breast milk by nursing infants.
Obstet Gynecol. 1994;84:263-265.
46. Mann CF. Clindamycin and breast-feeding. Pediatrics. 1980;
66:1030-1041.
47. OBrien T. Excretion of drugs in human milk. Am J Hosp Pharm.
1974;31:844-854.
48. Wilson JT. Milk/plasma ratios and contraindicated drugs. In Wilson JT,
ed. Drugs in Breast Milk. Balgowlah, Australia: ADIS Press; 1981:79.
49. Tran JH, Montakantikul P. The safety of antituberculosis medications
during breastfeeding. J Hum Lact. 1998;14:337-340.
50. Snider DE, Powell KE. Should women taking antituberculotic drugs
breast-feed? Arch Inter Med. 1984;144:589-590.
51. Kelsey JJ, Moser LR, Jennings JJ, Munger MA. Presence of azithromycin
breast milk concentrations: a case report. Am J Obstet Gynecol.
1994;170:1375-1376.
52. Biaxin [package insert]. Chicago, Ill: Abbott; May 1999.
53. Davey PG. The pharmacokinetics of clarithromycin and its 14-OH me-
tabolite. J Hosp Inf. 1991;19(suppl A):29-37.
54. Dynabac [package insert]. Tewksbury, Mass: Muro Pharmaceuticals; Oc-
tober 1999.
55. Sides GD, Cerimele BJ, Black HR, Bush U, DeSante KA. Pharmaco-
kinetics of dirithromycin. J Antimicrob Chemoth. 1993;31(suppl
C):65-75.
56. Knowles JA. Drugs in milk. Pediatr Currents. 1972;21:28-32.
57. Matsuda S. Transfer of antibiotics into maternal milk. Biol Res Pregnan
Perinatol. 1984;5:57-60.
58. Ito S, Blajchman A, Stephenson M, Eliopoulos C, Koren G. Prospective
follow-up of adverse reactions in breast-fed infants exposed to maternal
medication. Am J Obstet Gynecol. 1993;168:1393-1399.
59. Lassman HB, Puri SK, Ho I, Sabo R, Mezzino MJ, Pharmacokinetics of
roxithromycin (RU 965). J Clin Pharmacol. 1988;28:141-152.
J Hum Lact 17(1), 2001 Anti-Infective Agents
60. Young RA, Gonzalez JP, Sorkin EM. Roxithromycin: a review of its anti-
bacterial activity, pharmacokinetic properties and clinical efficacy.
Drugs. 1989;37:8-41.
61. Gardner DK, Galbe SG, Garter C. Simultaneous concentrations of
ciprofloxacin in breast milk and serum in mother and breast-fed infant.
Clin Pharm. 1992;11:352-354.
62. Cover DL, Mueller BA. Ciprofloxacin penetration into human breast
milk. DICP. 1990;24:703-704.
63. Giamerellou H, Kolokythas E, Petrikkos G, Gazis J, Aravantinos D,
Sfikakis P. Pharmacokinetics of three newer quinolones in pregnant and
lactating women. Am J Med. 1989;87(suppl 5A):49S-51S.
64. Harmon T, BurkhardtG, Appelbaum H. Perforated pseudomembranous
colitis in the breast-fed Infant. J Pediatr Surg. 1992;27:744-746.
65. Dan M, Weidekamm E, Sagiv r, Portmann R, Zakut H. Penetration of
fleroxacin into breastmilk and pharmacokinetics in lactating women.
Antimicrob Agents Chemother. 1993;293-296.
66. Traeger A, Peiker G. Excretion of nalidixic acid via mothers milk. Arch
Toxicol. 1980;S4:388-390.
67. Belton ME, Jones VR. Hemolytic anemia due to nalidixic acid. Lancet.
1965;2:691.
68. Murray EDS. Nalidixic acid in pregnancy. Br Med J. 1981;282:224.
69. Wise R. Norfloxacin: a review of pharmacology and tissue penetration. J
Antimicrob Chemother. 1984;13:59-64.
70. Noroxin [package insert]. West Point, Pa: Merck & Co.; October 1999.
71. Alghasham AA, Nahata MC. Clinical use of fluoroquinolones in chil-
dren. Ann Pharmacother. 2000;34:347-359.
72. Pefloxacin. Healthcare Series. Vol. 106. Micromedex; 1974-2000.
73. Chevalier X, Albengres E, Voisin MC, Tillement JP, Larget-Piet B. A case
of destructive polyarthropathy in a 17-year old youth following
pefloxacin treatment. Drug Safety. 1992;7:310-314.
74. Le LX, Fessard C, Noblet C, Ait SL, Moore N. Severe polyarthropathy in
an adolescent treated with pefloxacin. J Rheumatol. 1991;18:1941-1942.
75. Chang H, Chung MH, Kim JH, Kim JH. Pefloxacin-induced arthropathy
in an adolescent with brain abscess. Scand J Infect Dis. 1996;28:641-643.
76. Azad Khan AK, Truelove SC. Placental and mammary transfer of
sulphasalazine. Br Med J. 1979;2:1553.
77. Smadel JE, Woodward TE, Ley HL Jr., Lewthwaite R. Chloramphenicol
(Chloromycetin) in the treatment of Tsutsugamushi disease (scrub ty-
phus). J Clin Invest. 1949;28:1196-1215.
Downloaded from jhl.sagepub.com at BROWN UNIVERSITY on December 12, 2012
65
78. Havelka J, Hejzlar M, Popov V, Viktorinova D, Prochazka J. Excretion of
chloramphenicol in human milk. Chemotherapy. 1968;13:204-211.
79. Steen B, Rane A. Clindamycin passage into human milk. Br J Clin
Pharmacol. 1982;13:661-664.
80. Smith JA, Morgan JR, Rachlis AR, Papsin FR. Clindamycin in human
breast milk. Can Med Assoc J. 1975;112:806.
81. Erickson SH, Oppenheim GL, Smith GH. Metronidazole in breast milk.
Obstet Gynecol. 1981;57:48-50.
82. Passmore CM, McElnay JC, Rainey EA, DArcy PF. Metronidazole ex-
cretion in human milk and its effect on the suckling neonate. Br J Clin
Pharmacol. 1988;26:45-51.
83. Clements CJ. Metronidazole and breast feeding. NZ Med J. 1980;92:329.
Resumen
Debido a que muchos antibiticos se excretan por la
leche materna, los profesionales de la salud se
encuentran en la dificultad de escoger el medicamento
antibitico para las madres que amamantan con el mas
mnimo riesgo para sus bebs. Este artculo es uno de
una serie de tres artculos que discute el uso de agentes
anti-infecciosos durante la lactancia. Los autores
revisaron informacin general del uso y efectos
colaterales de diferentes clases de antibiticos. Tambin
se resume informacin, incluyendo concentraciones
que se encuentran en la leche, la relacin de
concentraciones leche-plasma y otras propiedades
farmacoquinticas, en una tabla que ayuda a los
profesionales para elegir los antibiticos que se
consideran seguros para utilizar en la madre que
amamanta.