Click here to load reader
Upload
samuel-gaytan-ramirez
View
212
Download
0
Embed Size (px)
Citation preview
8/13/2019 Lactobacillus CM Newsletter 2008
http://slidepdf.com/reader/full/lactobacillus-cm-newsletter-2008 1/5
Clinical Microbiology Newsletter 30:4,2008 © 2008 Elsevier 0196-4399/00 (see frontmatter) 23
IntroductionLactobacilli are non-spore-forming,
gram-positive rods that are an important
part of the normal human bacterial flora
commonly found in the mouth, gastro-
intestinal (GI) tract and female genito-
urinary tract (1-3). Microscopically,
these bacteria appear as non-motile, thin
rods varying in length from long to short.
They can also appear as coryneform
with a bent morphology or tend to grow
in chains. Most species of lactobacilli
are facultative anaerobes growing in
either the presence or absence of an
anaerobic environment. Only about 20%
of species isolated from humans are
obligate anaerobes. Lactobacilli tend to
grow well on blood agar (4). Some, but
not all, species will also grow on Lacto-
bacillus selective medium. Lactic acid
is the major metabolic end product of
lactobacilli during glucose fermentation
(2,3). Acetic and succinic acids are also
produced, but only in small amounts.
The GI tracts of various mammals
are commonly colonized with Lacto-
bacillus spp. (2,3). The most common
species of lactobacilli isolated from GI
tracts are Lactobacillus brevis, L. casei,
L. acidophilus, L. plantarum, L. fermen-
tum, and L. salivarius. Lactobacilli have
also been isolated from tooth plaque,
saliva, and the vaginal tracts of humans
and other mammals.
Lactobacilli are a rather diverse group
of bacteria, as is illustrated by their large
GC content, which ranges from 32 to 53
mol% (3). To date, greater than 70 differ-
ent species of Lactobacillus have been
identified; of these, only 34 have been
identified to the species level (2,3).
Pathogenesis and Clinical
SignificanceLactobacilli are required to maintain
a healthy GI tract and are not usually
considered to be pathogens in the healthy
host except when associated with dental
caries (5,6). They are considered pro-
tective organisms and are thought to
inhibit the growth of pathogenic organ-
isms via the production of lactic acid
and other metabolites. The clinical
significance of isolating Lactobacillus
from a normally sterile site is the sub-
ject of debate. When isolated by the
microbiology laboratory, some individ-
uals believe that lactobacilli should be
considered contaminants (7). Lactobac-
illi may go undetected in the laboratorybecause their growth requires special
media and extended incubation time.
Even after recovery, misidentification
can occur because morphologically
they resemble other genera, including
Corynebacterum, Clostridium, and
Streptococcus (5,8).
Although lactobacilli are considered
protective organisms, they have been
increasingly implicated as pathogens,
especially in the immunocompromised
patient (5,9-11). Numerous reports have
Lactobacillus: a ReviewChristine M. Slover, Pharm.D., Manager, Medical Information, Critical Care, Infectious Diseases, Astellas Pharma US, Inc.,
Deerfield, Illinois, and Larry Danziger, Pharm.D., Professor of Pharmacy, Associate Vice Chancellor for Research, University
of Illinois at Chicago, Chicago, Illinois
Abstract
Lactobacilli colonize the gastrointestinal and urinary tracts of humans, making them an integral part of the microbial flora.However, in certain circumstances, they can cause disease. Although lactobacilli are often misidentified as streptococci, it is
highly likely that these infections will be attributed to them due to current improvements in laboratory techniques. A recent resur-
gence in interesting natural products has caused an increased focus on the use of probiotics. Many of these probiotic formulations
contain Lactobacillus species. Although there have been reports of lactobacilli providing benefit in infectious diarrhea, the use of
these probiotic products in immunosuppressed or critically ill patients is not advised, since these populations are at increased risk
of developing infections due to lactobacilli.
Vol. 30, No. 4 www.cmnewsletter.com February 15, 2008
Mailing Address: Christine M. Slover,Pharm.D., Manager, Medical Information,Critical Care, Infectious Diseases, AstellasPharma US, Inc., Three Parkway North,
Deerfield, IL 60015. Tel.: 847-317-5028.Fax: 847-317-8229. Cell: 312-718-5334.
E-mail: [email protected]
ClinicalMicrobiologyNewsletter $ 8 8
8/13/2019 Lactobacillus CM Newsletter 2008
http://slidepdf.com/reader/full/lactobacillus-cm-newsletter-2008 2/5
been published of patients with AIDS or
neutropenia, or following organ trans-
plantation, with infections caused by
Lactobacillus spp. (9-11). Among the
more common clinical infections
reported to be caused by lactobacilli
are endocarditis, bacteremia, neonatal
meningitis, dental caries, abscesses,and chorioamnionitis (1,5,12). The three
most common infections caused by lac-
tobacilli are endocarditis, bacteremia,
and localized infections, such as
abscesses.
Endocarditis
Infective endocarditis (IE) with or
without associated bacteremia is the
most common infection caused by
lactobacilli reported in the literature
(1,6,12-14). Many of the patients who
develop Lactobacillus IE have recent
histories of dental procedures or poor
dentition, suggesting that this could beconsidered a risk factor, especially in
those patients with underlying immuno-
suppression (1,12,15). Patients who
develop IE also are also likely to have
underlying valvular heart disease (7,15).
The Lactobacillus species L. rham-
nosus and L. casei have been the
most frequently reported causes of
IE (1,12,14). The ability of these two
species of lactobacilli to cause IE is
thought to occur, in part, as a result of
their ability to induce platelet aggrega-
tion and generate fibrin, resulting in
clot formation (12,14,16). These char-
acteristics may allow the bacteria tocolonize thrombotic vegetations, per-
mitting the lactobacilli to grow and
evade host defenses (14). Oakey et al.
(14) reported that a factor X a-like
enzyme was produced by L. casei and
L. rhamnosus. Factor X a catalyzes steps
in the coagulation cascade leading to
the production of fibrin.
Numerous antibiotic treatment regi-
mens for endocarditis have been used.
Most patients receive penicillin with or
without an aminoglycoside (1,13,15,17).
These two regimens have been shown
to be moderately successful in treating
most cases of IE, but there are still a
number of treatment failures.
These disappointing results in the
treatment of IE may be due to the abil-
ity of lactobacilli to lower the pH of their environment via lactic acid pro-
duction. Kim et al. (17a) found that the
autolytic enzyme, which is essential for
the bactericidal effect of the β-lactam
antibiotics, is less active at a lower pH.
Sussman et al. (15) have suggested that
the large quantities of lactic acid pro-
duced by lactobacilli may hinder the
activity of the aminoglycoside antbi-
otics. This problem with loss of amino-
glycoside activity at lower pH levels
has been well described in the literature
in other infections caused by other
bacteria.
Monotherapy with vancomycin or
clindamycin has also been used for treat-
ment of patients with IE (1,7,15,17).
When either of these antibiotics was
used, patient outcomes have varied.
Overall, there tends to be decreased
susceptibility to vancomycin for Lac-
tobacillus spp. L. acidophilus and L.
delbrueckii seem to be the most suscep-
tible to vancomycin; however, these
species are the least likely to cause IE
(1,18). Griffiths et al. (17) reported in
vitro synergy with daptomycin and an
aminoglycoside against clinical isolates
of L. acidophilus and L. rhamnosus. This strategy may be a
potential treatment option for patients
with a penicillin allergy or when the
organism is vancomycin resistant.
Ciprofloxacin and other fluoroquino-
lones may also be considered treatment
options. In a retrospective review con-
ducted by Cannon et al. (1), Lactobac-
illus spp. were reported to be just over
60% susceptible to ciprofloxacin.
However, the newer fluoroquinolones,
such as moxifloxacin and gatifloxacin,
have better gram-positive coverage and
may potentially be better choices for
endocarditis treatment than ciprofloxacin.
The mean duration of treatment in
patients with endocarditis has been
reported to be about 49 days (1). Even
though there are multiple treatmentoptions for Lactobacillus endocarditis,
Cannon et al. (1) reported a mortality
of >20% in 61 patients with IE. Sig-
nificant morbidity is also frequently
reported in patients with endocarditis.
Patient outcomes have included valve
replacement, embolisms, and a high
risk of IE relapse (1,7,15).
Bacteremia
Lactobacillus bacteremia has a wide
array of clinical presentations; patients
can have severe sepsis or be asympto-
matic (10, 5,17,19-21). Fever is the most
common symptom in most patients, fol-lowed by leukocytosis and rigors (7).
Secondary lactobacillemias have been
reported in patients who have abscesses,
endocarditis, and pneumonia (10,15,17,
19-22).
Lactobacillus bacteremias are
believed to occur due to translocation
of bacteria across the intestinal mucosa
(11,23). Lactobacilli have been found to
be among the most frequently translo-
cating bacteria of the indigenous micro-
flora (23). When bacteria translocate
across the mucosa, they are typically
destroyed by the host immune system
(24). This again explains why immuno-suppression is the primary risk factor
for disease (7,21). Recent surgeries,
particularly abdominal procedures, have
also been implicated as causes of bac-
teremia (7,21). Recent antibiotic treat-
ment and prolonged hospitalization
have also been reported as risk factors
(19,21).
The treatment of bacteremia is simi-
lar to that for IE; the use of β-lactams
with or without aminoglycosides is the
24 0196-4399/00 (see frontmatter) © 2008 Elsevier Clinical Microbiology Newsletter 30:4,2008
8/13/2019 Lactobacillus CM Newsletter 2008
http://slidepdf.com/reader/full/lactobacillus-cm-newsletter-2008 3/5
Clinical Microbiology Newsletter 30:4,2008 © 2008 Elsevier 0196-4399/00 (see frontmatter) 25
most common therapy (1). The next
most commonly reported antibiotic
therapeutic regimen is combined therapy
using a cephalosporin with vancomycin.
In a recent review of the literature,
Cannon et al. (1) reported a mean
duration of treatment in patients with
bacteremia of approximately 14 days.Mortality attributed to lactobacillemia
has been reported to be relatively low
(1,7,19,21,25). In a review of 45 cases
of Lactobacillus bacteremia over a 15-
year period at a hospital in the United
States, only one patient death could be
attributed to lactobacillemia infection
(7). In many instances, patients will
have polymicrobial bacteremias, thus
making it difficult to truly discern if
infection caused by Lactobacillus spp.
was the specific cause of death (19,26).
Localized Infections
Localized infections due to Lac-tobacillus spp. are also increasingly
reported. Abdominal abscesses, pneu-
monia, other pulmonary infections,
and peritonitis are the most commonly
described in the literature (1). Once
again, underlying immunosuppression
is the major risk factor in these infec-
tions (5). Other risk factors are diabetes
and renal failure (1).
Treatment strategies for localized
infections differ from those for IE and
bacteremia, with most clinical isolates
showing susceptibility to erythromycin
and the fluoroquinolones (1). Mono-
therapy was employed most often inlocalized infection cases. High levels
of resistance have been reported to β-
lactam antibiotics and vancomycin in
these types of infections. Cannon et al.
(1) reported that half of the patients
with Lactobacillus sp. abscesses also
underwent surgical drainage as part of
their treatment. Mortality is low for
localized infections, with over 70%
of patients making full recoveries.
Probiotics
Due to a resurgence of interest in
“all-natural” products to treat illness,
Lactobacillus sp. supplemented prod-ucts have gained popularity. These
products are collectively termed probi-
otics. Aprobiotic is defined as a dietary
supplement consisting of living micro-
organisms that are found in normal
flora and have little, if any, pathogenic-
ity (27,28). When used, these products
are believed to have positive benefits
for health by preventing or treating
disease. Probiotics have been used in
a wide variety of gastrointestinal ill-
nesses, including infectious diarrhea,
irritable bowel syndrome, and inflam-
matory bowel disease. A number of
mechanisms have been proposed to
explain how probiotics exert theireffects. Acetic, propionic, and lactic
acids produced by lactobacilli may
reduce intestinal pH, thereby potentially
inhibiting the growth of pathogenic bac-
teria. However, the exact mechanism
by which lactobacilli may exert such
beneficial effects remains unknown.
In the last few years, the efficacy
of Lactobacillus sp. probiotics have
been extensively studied. Clinical trials
comparing Lactobacillus probiotics to
placebo or standard treatment options
have been done for numerous gastroin-
testinal disorders, attempts at cholesterol
management, and bacterial vaginoses,and even to attempt immunomodulation.
A meta-analysis of published studies
evaluating the efficacies of probiotics
(including an L. acidophilus mixture) in
preventing traveler’s diarrhea found the
pooled risk estimate to be 85%, show-
ing them to be effective and safe for
use (29). However, a recently published
double-blind, randomized trial using
L. acidophilus for prevention of trav-
eler’s diarrhea found the probiotic to be
ineffective (30). Comparable numbers
of cases of diarrhea were reported in the
two groups: 86.6 versus 63.9 cases per
100 person-months ( L. acidophilus
versus placebo, respectively; P = 0.29).
A randomized clinical trial conducted
in adult patients with chronic diverticu-
lar disease of the colon, currently in
remission, found that those patients
treated with a combination of mesala-
zine and L. casei DG had significant
improvements in their symptoms at
follow-up and more of these patients
remained in remission compared to
patients treated with either mesalazine
or the probiotic alone (31). Research
has also been conducted in pediatric
patients using probiotics for the treat-ment and prevention of a variety of GI
disorders. Several studies (32-35) have
reported success in treating irritable
bowel syndrome in school age children,
preventing diarrhea secondary to anti-
biotic treatment for respiratory infec-
tions, decreasing colic symptoms in
infants, and decreasing the duration of
acute diarrhea in young children living
in Thailand.
Since lactobacilli are common flora
of the urogenital tract, several studies
have been conducted to evaluate the
efficacies of probiotics in treating var-
ious conditions of the urogenital tract
in women. A recent study conducted inNigerian women found that two capsules
containing L. rhamnosus GR-1 and L.
reuteri RC-14 inserted intravaginally at
bedtime for 5 days were more success-
ful in treating bacterial vaginosis than
5 days of 0.75% metronidazole gel
inserted vaginally twice daily (30%
versus 75% positive for bacterial vagi-
nosis on day 6; P = 0.016) (36). How-
ever, a randomized trial conducted in
women being treated with antibiotics
for non-gynecological infections found
that post-antibiotic vulvovaginal can-
didiasis was not prevented by admini-
stering oral and/or vaginal probiotic
treatments containing L. rhamnosus
(37). Even for these two conditions,
bacterial vaginosis and vulvovaginal
candidiasis, the reports of probiotic
efficacy in the literature vary (38,39).
In 2006, the American Society
for Microbiology released a report
on probiotic use (40). The society
recommended that carefully designed,
randomized, placebo-controlled clinical
trials be conducted and also that in vitro
studies and in vivo models be standard-
ized to better study the effects of probi-
otics. The report also detailed the needfor affirming the potency and purity
of probiotic products prior to human
consumption. With renewed interest in
probiotics and some clinical studies
showing benefits of their use, this area
of research is likely to increase over
the next decade.
Antimicrobial Properties
As typical flora in the GI and uro-
genital tracts, lactobacilli have been
shown to prevent pathogenic bacteria
from causing infection. These bacteria
exhibit several properties that make
them useful for preventing infectiousdisease. One such property is the pro-
duction of low-molecular-weight anti-
microbials, also known as bacteriocins
(41). Bacteriocins are small proteins
produced by bacteria that can have
toxic effects on other bacteria (42,43).
These proteins are usually active against
identical or related species of bacteria
8/13/2019 Lactobacillus CM Newsletter 2008
http://slidepdf.com/reader/full/lactobacillus-cm-newsletter-2008 4/5
26 0196-4399/00 (see frontmatter) © 2008 Elsevier Clinical Microbiology Newsletter 30:4,2008
and eradicate neighboring bacteria by
attaching themselves to receptors on
their surfaces.
Lactobacilli also produce bacteriocin-
like substances. These compounds are
not as well defined chemically as bacter-
iocins, but they also control overgrowth
of potentially pathogenic bacteria (44).
Bacteriocin-like substances tend to have
broad spectra of action and inhibit both
gram-positive and gram-negative bacte-
ria, along with some fungi. McGroarty
and Reid (45) described an antimicro-
bial compound produced by L. casei
GR-1 that had activity against Escher-
ichia coli. The discovery of these agents
suggests that the presence of lactobac-
illi may prevent the overgrowth of var-
ious GI and urogenital bacteria, thus
preventing infection.
The presence of lactic acid andhydrogen peroxide, other byproducts
of lactobacillus metabolism, have also
been shown to be beneficial for control-
ling overgrowth of other, potentially
pathogenic bacteria (42,46). When
hydrogen peroxide-producing lacto-
bacilli are absent from the vaginal tract
of humans, there tends to be overgrowth
of catalase-negative bacteria, which in
turn causes bacterial vaginosis. Interest-
ingly, it has been reported that hydrogen
peroxide-producing Lactobacillus spp.
were isolated in only 6% of women
with the diagnosis of bacterial vaginosiscompared to 96% of women without the
disease (46). Antonio et al. (47) recently
reported that women who were not col-
onized with these hydrogen peroxide-
producing lactobacilli, either rectally
or vaginally, were 15 times more likely
to have bacterial vaginosis than women
who were colonized.
Lactic acid also inhibits the growth
of pathogenic microorganisms. Young
et al. (48) demonstrated in vitro inhibi-
tion of Candida albicans growth in a
mixed culture with lactobacilli. This
was attributed to a more acidic pH (pH
3.7 to 4.2) in the medium due to lactic
acid production by lactobacilli. All of
these characteristics make the lacto-
bacilli key bacteria in the human bac-
terial flora for keeping other “more
pathogenic” bacteria in check and not
allowing them to cause infection.
Food Industry
Lactobacilli and other lactic acid-
producing bacteria are also important
organisms used in industrial food pro-
duction (49). They are used to ferment
common foods, such as yogurt, cheese,
pickles, sauerkraut, and sourdough bread
(49,50). Fermentation produces lacticacid that causes a drop in pH. This drop
in pH then inhibits the growth of putre-
factive and pathogenic bacteria. In addi-
tion, these organisms also increase the
nutritional value of fermented foods.
This occurs because lactic acid-produc-
ing bacteria cause an increase in the pro-
duction of essential amino acids and
vitamins, along with an increased bio-
availability of minerals. Over the last
century, the food microbiology industry
has extensively studied lactobacilli and
deemed the bacteria safe for human
consumption.
Summary
Lactobacilli are an important part
of the human flora, but they can be
pathogenic under certain conditions.
The most common infections caused
by lactobacilli are bacteremias, IE, and
abscesses. These infections tend to occur
in immunosuppressed patients or those
patients with underlying anatomic
defects. Given the difficulty in isolating
these bacteria and the possibility that
they may often be misidentified, with
increasing improvements of our labo-
ratory technology it is possible that lac-
tobacilli will be implicated with greater
frequency as causative organisms in
infections.
In recent years, there has been an
increased focus on the use of probiotics,
such as Lactobacillus spp. Various spe-
cies of lactobacilli may provide benefit
in certain infectious diarrheas or other
illnesses. While the use of lactobacilli
has few significant adverse effects in
healthy people, they have been associ-
ated with some serious infections in
critically ill or immunosuppresed
patients (22,51).
More research is needed to expandour basic understanding of the conditions
under which lactobacilli cause infection,
especially with the mounting interest in
using Lactobacillus sp. products as
“natural forms” of disease treatment.
References
1. Cannon, J.P. et al. 2005. Pathogenic
relevance of Lactobacillus: a retrospec-
tive review of over 200 cases. Eur. J.
Clin. Microbiol. Infect. Dis. 24:31-40.
2. Madigan, M.T. et al. 2006. Prokaryotic
diversity: the bacteria, p 329-418. In
M.T. Madigan and J.M. Martinko (ed.),
Brock: biology of microorganisms.
Prentice Hall, Upper Saddle River, NJ.
3. Kononen, E. and W.G. Wade. 2007.
Propionibacterium, Lactobacillus,
Actinomyces, and other non-spore-
forming anaerobic gram-positive rods,
p. 872-888. In P.R. Murray (ed.),
Manual of clinical microbiology.
ASM Press, Washington, DC.
4. Summanen et al. (ed.). 1993. Appendix
A, p. 145. In Wadsworth anaerobic
bacteriology manual. Star Publishing
Company, Belmont, CA.
5. Aguirre, M. and M.D. Collins. 1993.
Lactic acid bacteria and human clinical
infection. J. Appl. Bacteriol. 75:95-107.
6. Sharpe, M.E., L.R. Hill, and S.P. Lapage.
1973. Pathogenic lactobacilli. J. Med.Microbiol. 6:281-286.
7. Husni, R.N. et al. 1997. Lactobacillus
bacteremia and endocarditis: review of
45 cases. Clin. Infect. Dis. 25:1048-
1055.
8. Holliman, R.E. and G.P. Bone. 1988.
Vancomycin resistance of clinical iso-
lates of lactobacilli. J. Infect. 16:279-283.
9. Abgrall, S. et al. 1997. Lactobacillus
casei infection in an AIDS patient. Eur.
J. Clin. Microbiol. Infect. Dis. 16:180-
182.
10. Chomarat, M. and D. Espinouse. 1991.
Lactobacillus rhamnosus septicemia in
patients with prolonged aplasia receiv-ing ceftazidime-vancomycin. Eur. J.
Clin. Microbiol. Infect. Dis. 10:44.
11. Schlegel, L., S. Lemerle, and P. Geslin.
1998. Lactobacillus species as oppor-
tunistic pathogens in immunocompro-
mised patients. Eur. J. Clin. Microbiol.
Infect. Dis. 17:887-888.
12. Harty D.W.S. et al. 1994. Pathogenic
potential of lactobacilli. Int. J. Food.
Microbiol. 24:179-189.
13. Naude, W.D.T. et al. 1988. Endocarditis
caused by Lactobacillus casei subspecies
rhamnosus: a case report. S. Afr. Med.
J. 73:612-614.
14. Oakey, H.F., D.W.S. Harty, and K.W.
Know. 1995. Enzyme production by
lactobacilli and the potential link
with infective endocarditis. J. Appl.
Bacteriol. 78:142-148.
15. Sussman, J.I. et al. 1986. Clinical mani-
festations and therapy of Lactobacillus
endocarditis: report of a case and review
of the literature. Rev. Infect. Dis. 8:771-
776.
8/13/2019 Lactobacillus CM Newsletter 2008
http://slidepdf.com/reader/full/lactobacillus-cm-newsletter-2008 5/5
Clinical Microbiology Newsletter 30:4,2008 © 2008 Elsevier 0196-4399/00 (see frontmatter) 27
16. Harty, D.W.S. et al. 1993. The aggrega-
tion of human platelets by Lactobacillus
species. J. Gen. Microbiol. 139:2945-
2951.
17. Griffiths, J.K., J.S. Daly, and R.A.
Dodge. 1992. Two cases of endocarditis
due to Lactobacillus species: antimicro-
bial susceptibility, review and discussion
of therapy. Clin. Infect. Dis. 15:250-255.
17a. Kim, K.S., J.O. Morrison, and A.S.
Bayer. 1982. Deficient autolytic enzyme
activity in antibiotic-tolerant lactobacilli.
Infect. Immun. 36:582-585.
18. Hamilton-Miller, J.M.T. and S. Shah.
1998. Vancomycin susceptibility as an
aid to the identification of lactobacilli.
Lett. Appl. Microbiol. 26:153-154.
19. Antony, S., C.W. Stratton, and J.S.
Dummer. 1996. Lactobacillus bacter-
emia: description of the clinical course
in adult patients without endocarditis.
Clin. Infect. Dis. 26:773-778.
20. Connor, J.P. and R.E. Buller. 1994. Case
report: Lactobacillus sepsis with pelvicabscess. Gynecol. Oncol. 54:99-100.
21. Salminen, M.K. et al. 2004. Lactobac-
illus bacteremia, clinical significance,
and patient outcome, with special focus
on probiotic L. rhamnosus GG. Clin.
Infect. Dis. 38:62-69.
22. Rogasi, P.G. et al. 1998. Lactobacillus
casei pneumonia and sepsis in a patient
with AIDS. Case report and review
of the literature. Ann. Ital. Med. Int.
13:180-182.
23. Naaber, P. et al. 2000. Translocation of
indigenous microflora in an experimen-
tal model of sepsis. J. Med. Microbiol.
49:431-439.
24. Berg, R.D. 1992. Translocation of
enteric bacteria in health and disease.
Gut-derived infectious toxic shock
(GITS). Curr. Stud. Hematol. Blood
Transfusion 52:44-65.
25. Salminen, M.K. et al. 2002. Lactobacil-
lus bacteremia during a rapid increase
in probiotic use of Lactobacillus rham-
nosus GG in Finland. Clin. Infect. Dis.
35:1155-1160.
26. Horwitch, C.A. et al. 1995. Lactobac-
illemia in three patients with AIDS.
Clin. Infect. Dis. 21:1460-1462.
27. Alvarez-Olmos, M.I. and R.A.
Oberhelman. 2001. Probiotic agents
and infectious diseases: a modern per-spective on traditional therapy. Clin.
Infect. Dis. 32:1567-1576.
28. Salminen, S. and H. Arvilommi. 2001.
Probiotics demonstrating efficacy in
clinical settings. Clin. Infect. Dis.
32:1577-1578.
29. McFarland, L.V. 2007. Meta-analysis
of probiotics for the prevention of
traveler’s diarrhea. Travel Med. Infect.
Dis. 5:97-105.
30. Briand, V. et al. 2006. Absence of
efficacy of nonviable Lactobacillus
acidophilus for the prevention of trav-
eler’s diarrhea: a randomized, double-
blind, controlled study. Clin. Infect.
Dis. 43:1170-1175.
31. Tursi, A. et al. 2006. Mesalazine and/
or Lactobacillus casei in preventing
recurrence of symptomatic uncompli-
cated diverticular disease of the colon:
a prospective, randomized, open-label
study. J. Clin. Gastroenterol. 40:312-
316.
32. Pant, A.R. et al. 1996. Lactobacillus GG
and acute diarrhea in young children in
the tropics. J. Trop. Pediatr. 42:162-165.33. Arvola, T. et al. 1999. Prophylactic
Lactobacillus GG reduces antibiotic-
associated diarrhea in children with
respiratory infections: a randomized
study. Pediatrics. 104:1-4.
34. Gawronska, A. et al. 2007. Arandom-
ized double-blind placebo-controlled
trial of Lactobacillus GG for abdominal
pain disorders in children. Aliment.
Pharmacol. Ther. 25:177-184.
35. Savino, F. et al. 2007. Lactobacillus
reuteri (American Type Culture
Collection Strain 55730) versus sime-
thicone in the treatment of infantile
colic: a prospective randomized study.
Pediatrics 119:124-130.
36. Anukam, K.C. et al. 2006. Clinical
study comparing probiotic Lactobac-
illus GR-1 and RC-14 with metronida-
zole vaginal gel to treat symptomatic
bacterial vaginosis. Microbes Infect.
8:2772-2776.
37. Pirotta, M. et al. 2004. Effect of lacto-
bacillus in preventing post-antibiotic
vulvovaginal candidiasis: a randomised
controlled trial. Br. Med. J. 329:548-552.
38. McGroarty, J.A. 1993. Probiotic use of
lactobacilli in the human female uro-
genital tract. FEMS Immunol. Med.
Microbiol. 6:251-264.
39. Hilton, E., P. Rindos, and H.D. Isenberg.1995. Lactobacillus GG vaginal suppos-
itories and vaginitis. J. Clin. Microbiol.
33:1433.
40. Walker, R., M. Buckley, and the
American Academy of Microbiology.
Probiotic microbes: the scientific basis.
http://www.asm.org . Accessed:
September 10, 2007.
41. Sablon, E., B. Contreras, and E.
Vandamme. 2000. Antimicrobial pep-tides of lactic acid bacteria: mode of
action, genetics and biosynthesis. Adv.
Biochem. Eng. Biotechnol. 68:21-60.
42. Tagg, J.R., A.S. Dajani, and L.W.
Wannamaker. 1976. Bacteriocins of
gram-positive bacteria. Bacteriol.
Rev. 40:722-756.
43. Reid, G. et al. 1990. Is there a role for
lactobacilli in prevention of urogenital
and intestinal infections? Clin. Microbiol.
Rev. 3:335-344.
44. Boris, S. and C. Barbes. 2000. Role
played by lactobacilli in controlling
the population of vaginal pathogens.
Microbes Infect. 2:543-546.
45. McGroarty, J.A. and G. Reid. 1988.
Detection of lactobacillus substance
that inhibits Escherichia coli. Can. J.
Microbiol. 34:974-978.
46. Eschenbach, D.A. et al. 1989. Preva-
lence of hydrogen peroxide-producing
Lactobacillus species in normal women
and women with bacterial vaginosis.
J. Clin. Microbiol. 27:251-256.
47. Antonio, M.A.D., L.K. Rabe, and
S.L. Hillier. 2005. Colonization of the
rectum by Lactobacillus species and
decreased risk of bacterial vaginosis.
J. Infect. Dis. 192:391-398.
48. Young, G., R.I. Krasner, and P.L.
Yudkofsky. 1956. Interactions of oralstrains of Candida albicans and lacto-
bacilli. J. Bacteriol. 75:525-529.
49. Hammes, W.P. and P.S. Tichaczek. 1997.
The potential of lactic acid bacteria for
the production of safe and wholesome
food. Z. Lebgensm. Unters. Forsch.
198:193-201.
50. Bernardeau, M., M. Guguen, and J.P.
Vernoux. 2006. Beneficial lactobacilli
in food and feed: long-term use, bio-
diversity and proposals for specific and
realistic safety assessments. FEMS
Microbial. Rev. 30:487-513.
51. Wood, G.C. et al. 2002. Lactobacillus
species as a cause of ventilator associ-ated pneumonia in a critically ill patient.
Pharmacotherapy 22:1180-1182.