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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 

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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

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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

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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.

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