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Abstract

The genus Lactobacillus is a taxonomically complex and is composed of over 170 species that cannot be easily differentiated phenotypically and often require molecular identification. Although they are part of the normal human gastrointestinal and vaginal flora, they can also be occasional human pathogens. They are extensively used in a variety of commercial products including probiotics. Their antimicrobial susceptibilities are poorly defined in part because of their taxonomic complexity and are compounded by the different methods recommended by Clinical Laboratory Standards Institute and International Dairy Foundation. Their use as probiotics for prevention of Clostridium difficile infection is prevalent among consumers worldwide but raises the question of will the use of any concurrent antibiotic effect their ability to survive. Lactobacillus species are generally acid resistant and are able to survive ingestion. They are generally resistant to metronidazole, aminoglycosides and ciprofloxacin with L. acidophilus being susceptible to penicillin and vancomycin, whereas L. rhamnosus and L. casei are resistant to metronidazole and vancomycin.

Lactobacillus acidophilus, Lactobacillus rhamnosus, Lactobacillus casei, Probiotics, Lactobacillus susceptibility

Lactobacillales is one of the diverse and phylogenetically heterogeneous orders of lactic acid producing bacteria that include the type genus Lactobacillus, as well as the genera Facklamia, Granulicatella, Leuconostoc, Pediococcus, and Streptococcus. They utilize carbohydrates fermentatively and produce lactic acid as a major end-product [1]. Lactobacillus spp. are facultatively anaerobic, catalase-negative, Gram-positive, non-spore-forming rods that often grow better under microaerophilic conditions. Their Gram stain morphology can vary, including as short, plump rods, long, slender rods, in chains or palisades. Their colonial morphology can vary from small to medium gray colonies that usually exhibit alpha hemolysis on blood agar. Lactobacilli grow on a variety of other media including MRS (Man, Rogosa, and Sharpe) agar where they appear as white, usually mucoid colonies. Identification of Lactobacillus species is by molecular means (16S rRNA genes) as phenotypic identification is generally unreliable.

Newer taxonomic methods have shown that some Lactobacillus species were erroneously assigned to the genus and have been reassigned to new or other genera including Atopobium (A. minutum and A. rimae), Eggerthia (E. catenaformis), Olsenella (O. uli), and Weisella (W. confusus). Lactobacillus is composed of over 170 species and 17 subspecies that are validly published and have good standing in nomenclature. In humans, they are indigenous in the gastrointestinal tract and vagina but can be occasional opportunistic pathogens. In the human gastrointestinal tract, there is a variety of ecological niches and various lactobacilli including L. fermentum, L. plantarum, L. casei, and L. rhamnosus that have been isolated from the gut. L. antri, L. gastricus, L. kalixensis, L. reuteri, and L. ultunensis have been isolated from the stomach mucosa [2]. Lactobacillus crispatus, L. gasseri, L. jensenii, L. vaginalis, and L. iners are common vaginal isolates [3]. Lactobacillus acidophilus occurs naturally in the human and animal gastrointestinal tract and mouth [4]. In general, the most common human clinical isolates are L. rhamnosus and L. casei.

COMMERCIAL USES

Ljungh and Wadström [5] published a comprehensive review on the probiotic benefits of lactic acid bacteria, including lactobacilli. Lactobacilli have long been used to make dairy products such as cheese and yogurt. They also have a high tolerance for very low pH conditions, especially those used to ferment foodstuffs such as mustard, cabbage, and olives, which optimizes their travel through the stomach. In the gut, Lactobacillus adhesion to the mucus layer of the gut wall is mediated by protein surface layer called the S-layer. In addition, some strains of lactobacilli produce antioxidants. Ljungh and Wadström [5] also review perhaps the most interesting probiotic potential of lactobacilli, the ability to immunomodulate human cells to achieve an anti-inflammatory response.

Lactobacillusacidophilus is considered to have probiotic characteristics. It is used commercially in many dairy products.

Lactobacillus casei including strain Shirota (YIT9029) (Yakult Honsha Co. Ltd Japan) complements the growth of L. acidophilus, a producer of the carbohydrate-digesting enzyme amylase. It is involved in the production and ripening of cheddar cheese and is the dominant species in naturally fermented Sicilian green olives.

Lactobacillus brevis, L. fermentum, and L. parabuchneri are the 3 major species of dairy obligate heterofermenters that, when present in cheese during ripening, can influence the flavor and texture of the final product. L. parabuchneri is also used to produce sourdough bread and ferment vegetables.

Lactobacillus bulgaricus, first identified in 1905 by the Bulgarian doctor Stamen Grigorov, was reclassified in 1984 as L. delbrueckii subsp. bulgaricus and is used for the production of yogurt. It is also found in other naturally fermented products and is used to preserve milk. It produces bacteriocins [6], which can be bactericidal in vitro.

Lactobacillus rhamnosus GG (ATCC 53103) (Valio Ltd. Finland) is a strain of L. rhamnosus isolated in 1983 from the intestinal tract of a healthy human being. Initially classified as L. acidophilus GG it was later reclassified as a strain of L. rhamnosus. The patent claims the L. rhamnosus GG (ATCC 53 103) strain include acid- and bile-stability, and great avidity for human intestinal mucosal cells.

Other Probiotic Lactobacillus strains isolated from the human intestinal microbiota and used as probiotics include L. acidophilus strain LB (Forest Laboratories Inc. New York), L. acidophilus strain NCFM (Danisco A/S, Denmark), L. johnsonii NCC 533 (Nestle, Switzerland), L. casei DN-114 001 (Danone, France), L. reuteri (DSM 17 938 BioGaia AB, Sweden), L. plantarum 299v (DSM 14 241, Probi AB, Sweden), L. fermentum ME-3 (University of Tartu and Tere AS, Estonia) and L. acidophilus CL1285, L. casei LBC80R, and L. rhamnosus CLR2 (BioK+, Laval, Quebec, Canada) [4, 7].

HUMAN INFECTIONS

Although Lactobacillus species are part of the normal commensal human flora, they have also been isolated from a variety of human infections [1, 8, 9]. Table 1 lists some of the clinical infections associated with Lactobacillus. Although probiotics are widely used, serious infections are rare in the literature and often involve comorbidity. In a 2 part study, Simkins et al [28] investigated probiotic use and bacteremia at an academic medical center. In a two-year period from 2007 to 2008, only 0.4% of patients used probiotics. From 2000 to 2008, the risk of probiotic associated bacteremia was 0.2% (2 of 1176 patients). Mazaide et al [29] reported the use of a probiotic combination of L. acidophilus CL1285, L. casei LBC80R and L. rhamnosus CLR2 (Bio-K+) in 31 382 patients over a 7 year period and found no episodes of Lactobacillus bacteremia.

Table 1.
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Types of Infections Associated With Lactobacillus Species

Infection TypeLactobacillus SpeciesReference
BacteremiaL. jensenii[8, 10, 11]
L. rhamnosus[8, 12, 13]
L. fermentum[8]
L. casei[8]
L. jensenii[8]
L. salivarius[8]
L. gasseri[8]
Other Lactobacillus species[8]
CholecystitisL. fermentum[14]
L. plantarum[15]
Dental abscess/cariesL. acidophilus[16]
L. casei/paracasei[16]
L. gasseri[16]
L. plantarum[16]
EmpyemaLactobacillus species[17, 18]
EndocarditisL. acidophilus[19]
L. casei[20]
L. jensenii[11, 21]
L. paracasei[22]
L. rhamnosus[12,23]
MeningitisL. rhamnosus[23]
PeritonitisL. fermentum[24]
L. paracasei[25]
L. plantarum[15]
L. rhamnosus[26]
Prosthetic knee infectionLactobacillus species[27]
PyelonephritisL. jensenii[10]
Infection TypeLactobacillus SpeciesReference
BacteremiaL. jensenii[8, 10, 11]
L. rhamnosus[8, 12, 13]
L. fermentum[8]
L. casei[8]
L. jensenii[8]
L. salivarius[8]
L. gasseri[8]
Other Lactobacillus species[8]
CholecystitisL. fermentum[14]
L. plantarum[15]
Dental abscess/cariesL. acidophilus[16]
L. casei/paracasei[16]
L. gasseri[16]
L. plantarum[16]
EmpyemaLactobacillus species[17, 18]
EndocarditisL. acidophilus[19]
L. casei[20]
L. jensenii[11, 21]
L. paracasei[22]
L. rhamnosus[12,23]
MeningitisL. rhamnosus[23]
PeritonitisL. fermentum[24]
L. paracasei[25]
L. plantarum[15]
L. rhamnosus[26]
Prosthetic knee infectionLactobacillus species[27]
PyelonephritisL. jensenii[10]
Table 1.
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Types of Infections Associated With Lactobacillus Species

Infection TypeLactobacillus SpeciesReference
BacteremiaL. jensenii[8, 10, 11]
L. rhamnosus[8, 12, 13]
L. fermentum[8]
L. casei[8]
L. jensenii[8]
L. salivarius[8]
L. gasseri[8]
Other Lactobacillus species[8]
CholecystitisL. fermentum[14]
L. plantarum[15]
Dental abscess/cariesL. acidophilus[16]
L. casei/paracasei[16]
L. gasseri[16]
L. plantarum[16]
EmpyemaLactobacillus species[17, 18]
EndocarditisL. acidophilus[19]
L. casei[20]
L. jensenii[11, 21]
L. paracasei[22]
L. rhamnosus[12,23]
MeningitisL. rhamnosus[23]
PeritonitisL. fermentum[24]
L. paracasei[25]
L. plantarum[15]
L. rhamnosus[26]
Prosthetic knee infectionLactobacillus species[27]
PyelonephritisL. jensenii[10]
Infection TypeLactobacillus SpeciesReference
BacteremiaL. jensenii[8, 10, 11]
L. rhamnosus[8, 12, 13]
L. fermentum[8]
L. casei[8]
L. jensenii[8]
L. salivarius[8]
L. gasseri[8]
Other Lactobacillus species[8]
CholecystitisL. fermentum[14]
L. plantarum[15]
Dental abscess/cariesL. acidophilus[16]
L. casei/paracasei[16]
L. gasseri[16]
L. plantarum[16]
EmpyemaLactobacillus species[17, 18]
EndocarditisL. acidophilus[19]
L. casei[20]
L. jensenii[11, 21]
L. paracasei[22]
L. rhamnosus[12,23]
MeningitisL. rhamnosus[23]
PeritonitisL. fermentum[24]
L. paracasei[25]
L. plantarum[15]
L. rhamnosus[26]
Prosthetic knee infectionLactobacillus species[27]
PyelonephritisL. jensenii[10]

In 2004 Salminen, et al [30] reviewed 89 patients between 1990 and 2000 with Lactobacillus bacteremia, including L. rhamnosus, L. rhamnosus GG, and other Lactobacillus species. In all cases, underlying diseases were mainly malignancies or serious gastrointestinal disorders such as hepatic cirrhosis and cholecystolithiasis. Among the 3 groups of lactobacilli isolated, there were no differences in the use of foreign devices of any kind (eg, peripheral or central venous catheters and/or urine catheters) or in the proportion of patients with immunosuppression; however, the majority of patients in all groups had undergone a surgical intervention. Polymicrobial infections occurred in 39% of the cases. They concluded that severe underlying diseases were a significant predictor for mortality, whereas treatment with antimicrobials effective in vitro was associated with lower mortality indicating their clinical significance.

In a 2006 follow-up study, Salminen et al [8] compared the antimicrobial therapy and susceptibilities in 85 patients between 1984 and 2000 of Lactobacillus bacteremia, including 46 L. rhamnosus strains and 39 other Lactobacillus species. In 22 cases, the L. rhamnosus strain was identical with the probiotic L. rhamnosus GG. Combination therapy was given to 83% of the patients, but in 54% of them, therapy included only 1 microbiologically active agent, according to results of the susceptibility tests. All isolates demonstrated low minimum inhibitory concentrations (MICs) against imipenem, piperacillin-tazobactam, erythromycin, and clindamycin. The ranges for the MICs of cephalosporins, which are frequently used to treat bacteremic infections, were wide, and very high MICs were demonstrated for many isolates. In general, the second-generation cephalosporin, cefuroxime, showed greater activity against lactobacilli, compared with the third-generation cephalosporin, ceftriaxone, which is in accordance with earlier observations. Mortality at 1 week was 12% among patients who presumably were receiving adequate treatment and 27% among patients who were receiving inadequate treatment. Overall mortality at 1 month was only 26% in this study. The relatively large number of patients with rapidly fatal underlying diseases diluted the beneficial effects of the antimicrobial therapy in both studies.

SUSCEPTIBILITY/ANTIBIOTIC RESISTANCE

The in vitro susceptibility testing of human isolates of Lactobacillus species has been limited to a variety of small studies often using diverse methodologies. The results should be of interest to both clinicians for the treatment of clinical infections, industry where the concomitant ingestion of antibiotics may influence the efficacy of their products, as well as the food industry that use lactobacilli for starter cultures of fermented foods. There have also been concerns about the potential transfer of resistance from lactobacilli to other organisms. Lactobacilli can produce strain-specific bacteriocins and bacteriocin-like products that can inhibit the growth of other organisms [4]. The taxonomic complexity of this genus makes study and generalizations difficult. Some species of lactobacilli are intrinsically resistant to vancomycin and aminoglycosides [8, 31], whereas other glycopeptides have variable activity against different species and strains [32, 33]. It has been postulated that this variability with other glycopeptides is related to the pentapeptide structure in nascent cell wall peptidoglycans. Vancomycin resistance is the best-characterized intrinsic resistance in lactobacilli. Instead of vancomycin binding to the d-alanine terminus of peptidoglycan residues on the cytoplasmic side of the cell wall, terminal d-alanine residues are replaced by d-lactate or d-serine in the muramyl-pentapeptide, preventing vancomycin binding [31].

Several genes responsible for atypical antibiotic resistance properties among lactobacilli have been described. Gueimonde et al [31] reported that although often susceptible to macrolides, chromosomal mutations in lactobacilli such as in L. rhamnosus can reduce the affinity of erythromycin for the ribosome. In addition, whereas lactobacilli are generally susceptible to penicillins, they are less so to cephalosporins. Antibiotic resistance determinants found in lactobacilli include hydrolysis, acetylation, enzymatic modification, efflux, ribosomal methylation, and ribosomal protection [31]. Tigecycline was noted to be active against a variety of Lactobacillus species (15 strains, MIC90, 0.5 µg/mL) including multidrug resistant strains of L. casei [34]. Chromosomal mutations in lactobacilli have been observed also, including the single mutation in the 23S rRNA gene that reduces the affinity of erythromycin to the ribosome [35]. Nawaz, et al [36] characterized the acquired resistance to erythromycin and tetracycline of 19 lactobacilli used to make dairy and fermentative vegetable products.

Many of our previous studies [33, 37] as well as those of others [32], have reported diverse Lactobacillus species together making it impossible to make specific comments about individual species. Consequently, we have re-compiled the results from several of our prior clinical studies from 2000 to 2012 [38–42]. Table 2 lists their molecular identification and human sources and Table 3 lists their susceptibilities. Re-analyses shows 4 distinct susceptibility patterns, 2 vancomycin resistant (VR-1,2) and 2 vancomycin susceptible (VS-1,2) groups. VR-1 consists of the L. casei/paracasei group and L. rhamnosus, the 2 most common clinical isolates and VR-2 several miscellaneous Lactobacillus species isolated from a variety of clinical sources. In addition to vancomycin resistance, the VR-1 group was more resistant to ceftriaxone and less susceptible to daptomycin than VR-2. Ertapenem was not active against VR-1 species, whereas imipenem was active for both VR-1 and VR-2. Clindamycin was more active against VR-2 strains. All groups were very susceptible to penicillin except for 2 isolates, 1 L. plantarum and 1 L. gasseri/johnsonii group were resistant (MIC 16 and >32 µg/mL, respectively). The VS-1 group consisted of the L. gasseri/johnsonii group and L. jensenii whereas VS-2 consisted of several less frequently isolated clinical strains. Vancomycin, ertapenem, and imipenem were active against groups VS-1 and VS-2. Linezolid was not active against VS-2 (MIC 16 µg/mL). Levofloxacin was active (MIC50 2 µg/mL) against half of the strains tested in our studies.

Table 2.
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Source Listing of 70 Strains of Lactobacillus Representing 17 Species

AbdominalBloodFGU-endo/pelvicaFGU-vagbOralSoft TissueRespiratoryStoolUrinary
L. acidophilus (1)1
L. animalis (1)1
L. antrumi (1)1
L. casei/ paracasei (10)712
L. crispatus (2)11
L. delbrueckii (1)1
L. fermentum (5)23
L. gasseri/ johnsonii (15)722121
L. iners (2)11
L. jensenii (5)1211
L. mucosae (1)1
L. oris (2)11
L. plantarum (1)1
L. reuteri (1)1
L. rhamnosus (15)91131
L. salivarius (2)11
L. vaginalis (5)2111
AbdominalBloodFGU-endo/pelvicaFGU-vagbOralSoft TissueRespiratoryStoolUrinary
L. acidophilus (1)1
L. animalis (1)1
L. antrumi (1)1
L. casei/ paracasei (10)712
L. crispatus (2)11
L. delbrueckii (1)1
L. fermentum (5)23
L. gasseri/ johnsonii (15)722121
L. iners (2)11
L. jensenii (5)1211
L. mucosae (1)1
L. oris (2)11
L. plantarum (1)1
L. reuteri (1)1
L. rhamnosus (15)91131
L. salivarius (2)11
L. vaginalis (5)2111

a FGU-endo/pelvic: Female genitourinary, endometrial-pelvic.

b FGU-vag: Female genitourinary, vaginal.

Table 2.
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Source Listing of 70 Strains of Lactobacillus Representing 17 Species

AbdominalBloodFGU-endo/pelvicaFGU-vagbOralSoft TissueRespiratoryStoolUrinary
L. acidophilus (1)1
L. animalis (1)1
L. antrumi (1)1
L. casei/ paracasei (10)712
L. crispatus (2)11
L. delbrueckii (1)1
L. fermentum (5)23
L. gasseri/ johnsonii (15)722121
L. iners (2)11
L. jensenii (5)1211
L. mucosae (1)1
L. oris (2)11
L. plantarum (1)1
L. reuteri (1)1
L. rhamnosus (15)91131
L. salivarius (2)11
L. vaginalis (5)2111
AbdominalBloodFGU-endo/pelvicaFGU-vagbOralSoft TissueRespiratoryStoolUrinary
L. acidophilus (1)1
L. animalis (1)1
L. antrumi (1)1
L. casei/ paracasei (10)712
L. crispatus (2)11
L. delbrueckii (1)1
L. fermentum (5)23
L. gasseri/ johnsonii (15)722121
L. iners (2)11
L. jensenii (5)1211
L. mucosae (1)1
L. oris (2)11
L. plantarum (1)1
L. reuteri (1)1
L. rhamnosus (15)91131
L. salivarius (2)11
L. vaginalis (5)2111

a FGU-endo/pelvic: Female genitourinary, endometrial-pelvic.

b FGU-vag: Female genitourinary, vaginal.

Table 3.
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MIC Activities of Various Antimicrobial Agents (µg/mL) Against 70 Strains of Molecularly Identified Lactobacillus Species Isolated From Human Sources and Compiled From Several in vitro Studies From 2000 to 2012 [38–42]

Organism / DrugNo.aRangeMIC50MIC90
Vancomycin Resistant
 Group 1b
  Penicillin140.25–40.52
  Ampicillin151–414
  Ceftriaxone178–>32>32>32
  Cefoxitin14>128>128>128
  Piperacillin-tazobactam240.5–814
  Imipenem240.25–1628
  Ertapenem1016–>16>16>16
  Vancomycin17>64>64>64
  Clindamycin190.06–10.251
  Daptomycin151–424
  Linezolid102–444
  Levofloxacin41–22…
 Group 2c
  Penicillin130.125–>320.52
  Ampicillin120.125–80.252
  Ceftriaxone41–164…
  Cefoxitin916–>128>128…
  Piperacillin-tazobactam130.5–414
  Imipenem15≤0.015–0.50.030.25
  Ertapenem80.5–41…
  Vancomycin1632–>32>32>32
  Clindamycin13≤0.03–0.5≤0.030.5
  Daptomycin80.125–0.50.25…
  Linezolid61–84…
  Levofloxacin61–81…
Vancomycin Susceptible
 Group 1d
  Penicillin100.05–0.250.1250.25
  Ampicillin17≤0.125–10.251
  Ceftriaxone52–82…
  Cefoxitin118–>12832128
  Piperacillin-tazobactam180.25–40.51
  Imipenem180.06–10.250.5
  Ertapenem81–84…
  Vancomycin180.5–212
  Clindamycin170.06–412
  Daptomycin130.5–>32432
  Linezolid121–444
  Levofloxacin11616…
 Group 2e
  Penicillin4≤0.06–0.50.125…
  Ampicillin40.125–10.25…
  Ceftriaxone31–44…
  Cefoxitin38–1616…
  Piperacillin-tazobactam60.25–40.5…
  Imipenem50.06–0.250.125…
  Ertapenem40.5–40.5…
  Vancomycin70.5–21…
  Clindamycin6≤0.03–0.1250.06…
  Daptomycin30.5–11…
  Linezolid44–>32>32…
  Levofloxacin20.50.5…
Organism / DrugNo.aRangeMIC50MIC90
Vancomycin Resistant
 Group 1b
  Penicillin140.25–40.52
  Ampicillin151–414
  Ceftriaxone178–>32>32>32
  Cefoxitin14>128>128>128
  Piperacillin-tazobactam240.5–814
  Imipenem240.25–1628
  Ertapenem1016–>16>16>16
  Vancomycin17>64>64>64
  Clindamycin190.06–10.251
  Daptomycin151–424
  Linezolid102–444
  Levofloxacin41–22…
 Group 2c
  Penicillin130.125–>320.52
  Ampicillin120.125–80.252
  Ceftriaxone41–164…
  Cefoxitin916–>128>128…
  Piperacillin-tazobactam130.5–414
  Imipenem15≤0.015–0.50.030.25
  Ertapenem80.5–41…
  Vancomycin1632–>32>32>32
  Clindamycin13≤0.03–0.5≤0.030.5
  Daptomycin80.125–0.50.25…
  Linezolid61–84…
  Levofloxacin61–81…
Vancomycin Susceptible
 Group 1d
  Penicillin100.05–0.250.1250.25
  Ampicillin17≤0.125–10.251
  Ceftriaxone52–82…
  Cefoxitin118–>12832128
  Piperacillin-tazobactam180.25–40.51
  Imipenem180.06–10.250.5
  Ertapenem81–84…
  Vancomycin180.5–212
  Clindamycin170.06–412
  Daptomycin130.5–>32432
  Linezolid121–444
  Levofloxacin11616…
 Group 2e
  Penicillin4≤0.06–0.50.125…
  Ampicillin40.125–10.25…
  Ceftriaxone31–44…
  Cefoxitin38–1616…
  Piperacillin-tazobactam60.25–40.5…
  Imipenem50.06–0.250.125…
  Ertapenem40.5–40.5…
  Vancomycin70.5–21…
  Clindamycin6≤0.03–0.1250.06…
  Daptomycin30.5–11…
  Linezolid44–>32>32…
  Levofloxacin20.50.5…

Abbreviation: MIC, minimum inhibitory concentration.

a No., number tested.

bL. casei/paracasei group (10) and L. rhamnosus (15).

cL. animalis (1), L. antrumi (1), L. fermentum (5), L. mucosae (1), L. plantarum (1), L. reuteri (1), L. salivarius (2) and L. vaginalis (5).

dL. gasseri/johnsonii group (15), L. jensenii (5).

eL. acidophilus (1), L. crispatus (2), L. delbrueckii (1), L. iners (2) and L. oris (2).

Table 3.
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MIC Activities of Various Antimicrobial Agents (µg/mL) Against 70 Strains of Molecularly Identified Lactobacillus Species Isolated From Human Sources and Compiled From Several in vitro Studies From 2000 to 2012 [38–42]

Organism / DrugNo.aRangeMIC50MIC90
Vancomycin Resistant
 Group 1b
  Penicillin140.25–40.52
  Ampicillin151–414
  Ceftriaxone178–>32>32>32
  Cefoxitin14>128>128>128
  Piperacillin-tazobactam240.5–814
  Imipenem240.25–1628
  Ertapenem1016–>16>16>16
  Vancomycin17>64>64>64
  Clindamycin190.06–10.251
  Daptomycin151–424
  Linezolid102–444
  Levofloxacin41–22…
 Group 2c
  Penicillin130.125–>320.52
  Ampicillin120.125–80.252
  Ceftriaxone41–164…
  Cefoxitin916–>128>128…
  Piperacillin-tazobactam130.5–414
  Imipenem15≤0.015–0.50.030.25
  Ertapenem80.5–41…
  Vancomycin1632–>32>32>32
  Clindamycin13≤0.03–0.5≤0.030.5
  Daptomycin80.125–0.50.25…
  Linezolid61–84…
  Levofloxacin61–81…
Vancomycin Susceptible
 Group 1d
  Penicillin100.05–0.250.1250.25
  Ampicillin17≤0.125–10.251
  Ceftriaxone52–82…
  Cefoxitin118–>12832128
  Piperacillin-tazobactam180.25–40.51
  Imipenem180.06–10.250.5
  Ertapenem81–84…
  Vancomycin180.5–212
  Clindamycin170.06–412
  Daptomycin130.5–>32432
  Linezolid121–444
  Levofloxacin11616…
 Group 2e
  Penicillin4≤0.06–0.50.125…
  Ampicillin40.125–10.25…
  Ceftriaxone31–44…
  Cefoxitin38–1616…
  Piperacillin-tazobactam60.25–40.5…
  Imipenem50.06–0.250.125…
  Ertapenem40.5–40.5…
  Vancomycin70.5–21…
  Clindamycin6≤0.03–0.1250.06…
  Daptomycin30.5–11…
  Linezolid44–>32>32…
  Levofloxacin20.50.5…
Organism / DrugNo.aRangeMIC50MIC90
Vancomycin Resistant
 Group 1b
  Penicillin140.25–40.52
  Ampicillin151–414
  Ceftriaxone178–>32>32>32
  Cefoxitin14>128>128>128
  Piperacillin-tazobactam240.5–814
  Imipenem240.25–1628
  Ertapenem1016–>16>16>16
  Vancomycin17>64>64>64
  Clindamycin190.06–10.251
  Daptomycin151–424
  Linezolid102–444
  Levofloxacin41–22…
 Group 2c
  Penicillin130.125–>320.52
  Ampicillin120.125–80.252
  Ceftriaxone41–164…
  Cefoxitin916–>128>128…
  Piperacillin-tazobactam130.5–414
  Imipenem15≤0.015–0.50.030.25
  Ertapenem80.5–41…
  Vancomycin1632–>32>32>32
  Clindamycin13≤0.03–0.5≤0.030.5
  Daptomycin80.125–0.50.25…
  Linezolid61–84…
  Levofloxacin61–81…
Vancomycin Susceptible
 Group 1d
  Penicillin100.05–0.250.1250.25
  Ampicillin17≤0.125–10.251
  Ceftriaxone52–82…
  Cefoxitin118–>12832128
  Piperacillin-tazobactam180.25–40.51
  Imipenem180.06–10.250.5
  Ertapenem81–84…
  Vancomycin180.5–212
  Clindamycin170.06–412
  Daptomycin130.5–>32432
  Linezolid121–444
  Levofloxacin11616…
 Group 2e
  Penicillin4≤0.06–0.50.125…
  Ampicillin40.125–10.25…
  Ceftriaxone31–44…
  Cefoxitin38–1616…
  Piperacillin-tazobactam60.25–40.5…
  Imipenem50.06–0.250.125…
  Ertapenem40.5–40.5…
  Vancomycin70.5–21…
  Clindamycin6≤0.03–0.1250.06…
  Daptomycin30.5–11…
  Linezolid44–>32>32…
  Levofloxacin20.50.5…

Abbreviation: MIC, minimum inhibitory concentration.

a No., number tested.

bL. casei/paracasei group (10) and L. rhamnosus (15).

cL. animalis (1), L. antrumi (1), L. fermentum (5), L. mucosae (1), L. plantarum (1), L. reuteri (1), L. salivarius (2) and L. vaginalis (5).

dL. gasseri/johnsonii group (15), L. jensenii (5).

eL. acidophilus (1), L. crispatus (2), L. delbrueckii (1), L. iners (2) and L. oris (2).

Table 4 lists the collated susceptibilities of the most commonly isolated lactobacilli from our studies, a bacteremia study [8] and from commercial dairy and fermentative products [36] against a variety of agents. For the most part, the susceptibilities were similar, regardless of source, except that ciprofloxacin was less active against commercial strains of L. casei, and erythromycin and clindamycin were less active against commercial strains of L. fermentum.

Table 4.
Open in new tab

Susceptibilities (MICs, µg/mL) of Various Lactobacillus Species More Commonly Isolated From Human Sources and Found in Commercial Products to Selected Antimicrobial Agents Using Various Methodologiesa

Species/Drug [no. isolates]Goldstein [38–42]
Salminen [8]
Nawaz [36]
No.RangeMIC90No.RangeMIC90No.RangeMIC90
L. acidophilus
 Penicillin70.125–2…
 Ampicillin70.5…
 Erythromycin70.06–4…
 Clindamycin70.06–0.25…
 Vancomycin70.125–0.5…
 Ciprofloxacin72–16…
 Bacitracin70.5–2…
 Chloramphenicol70.25–4…
 Tetracycline70.5–2…
 Gentamicin72–64…
L. casei
 Penicillin70.5–2…120.25–4251–2…
 Ampicillin71–4…120.5–4250.125–1…
 Cefuroxime122–>25664
 Ceftriaxone88–>64…128–>256>256
 Cefoxitin7>128…
 Piperacillin-tazobactam90.5–8…120.5–84
 Ertapenem5>16…
 Imipenem90.25–8…120.5–22
 Erythromycin12≤0.03–0.250.1250.06–0.5…
 Clindamycin80.06–0.5…120.06–0.250.2550.5…
 Vancomycin7>64…12>256>2565>256…
 Ciprofloxacin120.5–4158–32…
 Bacitracin50.5–4…
 Chloramphenicol50.25–2…
 Daptomycin71–4…
 Linezolid54…
 Doxycycline120.25–11
 Tetracycline50.5–1…
 Gentamicin54–128…
 Netilmicin120.12–44
 Tobramucin120.5–1616
L. delbrueckii ssp. bulgaricus
 Penicillin10.125130.06.–0.250.25
 Ampicillin10.125130.125–0.250.25
 Cefoxitin116
 Piperacillin-tazobactam10.25
 Imipenem10.125
 Ertapenem10.5
 Erythromycin130.06–0.50.5
 Clindamycin1≤0.03130.06–0.50.5
 Vancomycin10.5130.125–0.50.5
 Daptomycin10.5
 Ciprofloxacin132–3232
 Levofloxacin10.5
 Bacitracin130.05–22
 Chloramphenicol130.25––162
 Tetracycline130.125–22
 Gentamicin134–6464
L. fermentum
 Penicillin30.25–0.5…120.25–0.50.2550.125–0.5…
 Ampicillin30.125–0.25…120.12–0.250.2550.125–0.5…
 Cefuroxime120.25–168
 Ceftriaxone116…120.5–>25632
 Cefoxitin2>128…
 Piperacillin-tazobactam50.5–2…121–21
 Imipenem5≤0.015–0.5…12≤0.03–10.06
 Ertapenem20.5–1…
 Erythromycin12≤0.03–0.250.1250.125–>64…
 Clindamycin3≤0.03…12≤0.06–0.250.0650.125–>64…
 Vancomycin532–>32…12>256>2565>256>256
 Daptomycin30.25…
 Linezolid24…
 Ciprofloxacin124–323254–8…
 Levofloxacin14…
 Bacitracin52–4…
 Chloramphenicol50.25–8…
 Doxycycline120.5–44
 Tetracycline50.125–4…
 Gentamicin54–128…
 Netilmicin120.06–20.25
 Tobramycin120.5–84
L. parabuchnerii
 Penicillin120.06–0.250.25
 Ampicillin120.125–0.50.5
 Erythromycin120.06–0.50.125
 Clindamycin120.06–0.50.125
 Vancomycin120.125–0.50.5
 Ciprofloxacin124–3232
 Bacitracin120.125–22
 Chloramphenicol120.25–162
 Tetracycline128–3232
 Gentamicin121–128128
L. plantarum
 Penicillin1>32…18…70.125–1…
 Ampicillin2…10.5…70.125–0.5…
 Cefuroxime12…
 Ceftriazone11…
 Piperacillin-tazobactam11…
 Erythromycin70.06–32…
 Clindamycin10.5…12…70.06–0.125…
 Vancomycin1>32…1>256…7>256…
 Imipenem1≤0.06…1≤0.03…
 Ertapenem14…
 Ciprofloxacin1>32…72–32…
 Bacitracin70.5–8…
 Chloramphenicol70.25–2…
 Tetracycline71–>128…
 Gentamicin74–128…
 Netilmycin11…
 Tobramycin18…
L. rhamnosus GG
 Penicillin220.25–21
 Ampicillin220.5–21
 Cefuroxime222–168
 Ceftriaxone22128–>256>256
 Piperacillin-tazobactam221–21
 Imipenem220.5–22
 Erythromycin220.06–0.250.25
 Clindamycin220.06–0.50.25
 Vancomycin22>256>256
 Ciprofloxacin220.25–11
 Doxycycline220.25–10.5
 Netilmicin222–44
 Tobramycin224–3216
L. rhamnosus, not GG*
 Penicillin70.25–4…240.12–4441–2…
 Ampicillin81–4…240.25–8240.5–1…
 Cefuroxime242–128128
 Ceftriaxone916–64…242–>256>256
 Cefoxitin7>128…
 Piperacillin-tazobactam151–84240.5–84
 Imipenem152–168240.25–44
 Ertapenem516–>16…
 Erythromycin24≤0.03–0.250.2540.06–0.5…
 Clindamycin110.06–11240.06–0.50.540.06–0.5…
 Vancomycin10>32>3224>256>2574>256…
 Daptomycin81–4…
 Linezolid52–4…
 Ciprofloxacin240.25–2144–32…
 Levofloxacin31–2…
 Bacitracin40.5–4…
 Chloramphenicol40.25–2…
 Doxycycline240.25–0.50.5
 Tetracycline41–4…
 Gentamicin432–128…
 Netilmicin240.5–44
 Tobramycin242–3216
L. salivarius
 Penicillin20.125–0.2530.12–0.25…50.125–>64…
 Ampicillin20.25–0.530.12–0.25…50.125–0.25…
 Cefuroxime30.25–0.5…
 Ceftriaxone1130.5–1…
 Cefoxitin116
 Piperacillin-tazobactam1131…
 Imipenem20.03–0.1253≤0.03–0.5…
 Ertapenam21
 Erythromycin30.06–0.25…50.06–>64…
 Clindamycin20.25–0.53≤0.03–0.25…50.06–0.5…
 Vancomycin2>323>256…5>256…
 Linezolid11
 Ciprofloxacin30.5–1…54–32…
 Levofloxacin11
 Bacitracin52–8…
 Chloramphenicol50.25–32…
 Doxycycline30.25–1…
 Tetracycline5>128…
 Gentamicin516–128…
 Netilmicin30.25–4…
 Tobramycin31–32…
Species/Drug [no. isolates]Goldstein [38–42]
Salminen [8]
Nawaz [36]
No.RangeMIC90No.RangeMIC90No.RangeMIC90
L. acidophilus
 Penicillin70.125–2…
 Ampicillin70.5…
 Erythromycin70.06–4…
 Clindamycin70.06–0.25…
 Vancomycin70.125–0.5…
 Ciprofloxacin72–16…
 Bacitracin70.5–2…
 Chloramphenicol70.25–4…
 Tetracycline70.5–2…
 Gentamicin72–64…
L. casei
 Penicillin70.5–2…120.25–4251–2…
 Ampicillin71–4…120.5–4250.125–1…
 Cefuroxime122–>25664
 Ceftriaxone88–>64…128–>256>256
 Cefoxitin7>128…
 Piperacillin-tazobactam90.5–8…120.5–84
 Ertapenem5>16…
 Imipenem90.25–8…120.5–22
 Erythromycin12≤0.03–0.250.1250.06–0.5…
 Clindamycin80.06–0.5…120.06–0.250.2550.5…
 Vancomycin7>64…12>256>2565>256…
 Ciprofloxacin120.5–4158–32…
 Bacitracin50.5–4…
 Chloramphenicol50.25–2…
 Daptomycin71–4…
 Linezolid54…
 Doxycycline120.25–11
 Tetracycline50.5–1…
 Gentamicin54–128…
 Netilmicin120.12–44
 Tobramucin120.5–1616
L. delbrueckii ssp. bulgaricus
 Penicillin10.125130.06.–0.250.25
 Ampicillin10.125130.125–0.250.25
 Cefoxitin116
 Piperacillin-tazobactam10.25
 Imipenem10.125
 Ertapenem10.5
 Erythromycin130.06–0.50.5
 Clindamycin1≤0.03130.06–0.50.5
 Vancomycin10.5130.125–0.50.5
 Daptomycin10.5
 Ciprofloxacin132–3232
 Levofloxacin10.5
 Bacitracin130.05–22
 Chloramphenicol130.25––162
 Tetracycline130.125–22
 Gentamicin134–6464
L. fermentum
 Penicillin30.25–0.5…120.25–0.50.2550.125–0.5…
 Ampicillin30.125–0.25…120.12–0.250.2550.125–0.5…
 Cefuroxime120.25–168
 Ceftriaxone116…120.5–>25632
 Cefoxitin2>128…
 Piperacillin-tazobactam50.5–2…121–21
 Imipenem5≤0.015–0.5…12≤0.03–10.06
 Ertapenem20.5–1…
 Erythromycin12≤0.03–0.250.1250.125–>64…
 Clindamycin3≤0.03…12≤0.06–0.250.0650.125–>64…
 Vancomycin532–>32…12>256>2565>256>256
 Daptomycin30.25…
 Linezolid24…
 Ciprofloxacin124–323254–8…
 Levofloxacin14…
 Bacitracin52–4…
 Chloramphenicol50.25–8…
 Doxycycline120.5–44
 Tetracycline50.125–4…
 Gentamicin54–128…
 Netilmicin120.06–20.25
 Tobramycin120.5–84
L. parabuchnerii
 Penicillin120.06–0.250.25
 Ampicillin120.125–0.50.5
 Erythromycin120.06–0.50.125
 Clindamycin120.06–0.50.125
 Vancomycin120.125–0.50.5
 Ciprofloxacin124–3232
 Bacitracin120.125–22
 Chloramphenicol120.25–162
 Tetracycline128–3232
 Gentamicin121–128128
L. plantarum
 Penicillin1>32…18…70.125–1…
 Ampicillin2…10.5…70.125–0.5…
 Cefuroxime12…
 Ceftriazone11…
 Piperacillin-tazobactam11…
 Erythromycin70.06–32…
 Clindamycin10.5…12…70.06–0.125…
 Vancomycin1>32…1>256…7>256…
 Imipenem1≤0.06…1≤0.03…
 Ertapenem14…
 Ciprofloxacin1>32…72–32…
 Bacitracin70.5–8…
 Chloramphenicol70.25–2…
 Tetracycline71–>128…
 Gentamicin74–128…
 Netilmycin11…
 Tobramycin18…
L. rhamnosus GG
 Penicillin220.25–21
 Ampicillin220.5–21
 Cefuroxime222–168
 Ceftriaxone22128–>256>256
 Piperacillin-tazobactam221–21
 Imipenem220.5–22
 Erythromycin220.06–0.250.25
 Clindamycin220.06–0.50.25
 Vancomycin22>256>256
 Ciprofloxacin220.25–11
 Doxycycline220.25–10.5
 Netilmicin222–44
 Tobramycin224–3216
L. rhamnosus, not GG*
 Penicillin70.25–4…240.12–4441–2…
 Ampicillin81–4…240.25–8240.5–1…
 Cefuroxime242–128128
 Ceftriaxone916–64…242–>256>256
 Cefoxitin7>128…
 Piperacillin-tazobactam151–84240.5–84
 Imipenem152–168240.25–44
 Ertapenem516–>16…
 Erythromycin24≤0.03–0.250.2540.06–0.5…
 Clindamycin110.06–11240.06–0.50.540.06–0.5…
 Vancomycin10>32>3224>256>2574>256…
 Daptomycin81–4…
 Linezolid52–4…
 Ciprofloxacin240.25–2144–32…
 Levofloxacin31–2…
 Bacitracin40.5–4…
 Chloramphenicol40.25–2…
 Doxycycline240.25–0.50.5
 Tetracycline41–4…
 Gentamicin432–128…
 Netilmicin240.5–44
 Tobramycin242–3216
L. salivarius
 Penicillin20.125–0.2530.12–0.25…50.125–>64…
 Ampicillin20.25–0.530.12–0.25…50.125–0.25…
 Cefuroxime30.25–0.5…
 Ceftriaxone1130.5–1…
 Cefoxitin116
 Piperacillin-tazobactam1131…
 Imipenem20.03–0.1253≤0.03–0.5…
 Ertapenam21
 Erythromycin30.06–0.25…50.06–>64…
 Clindamycin20.25–0.53≤0.03–0.25…50.06–0.5…
 Vancomycin2>323>256…5>256…
 Linezolid11
 Ciprofloxacin30.5–1…54–32…
 Levofloxacin11
 Bacitracin52–8…
 Chloramphenicol50.25–32…
 Doxycycline30.25–1…
 Tetracycline5>128…
 Gentamicin516–128…
 Netilmicin30.25–4…
 Tobramycin31–32…

Abbreviation: MIC, minimum inhibitory concentration.

a Goldstein, agar dilution, Clinical Laboratory Standards Institute; Salminen, Etest; Nawaz, International Organization of Standardization/International Dairy Federation.

Table 4.
Open in new tab

Susceptibilities (MICs, µg/mL) of Various Lactobacillus Species More Commonly Isolated From Human Sources and Found in Commercial Products to Selected Antimicrobial Agents Using Various Methodologiesa

Species/Drug [no. isolates]Goldstein [38–42]
Salminen [8]
Nawaz [36]
No.RangeMIC90No.RangeMIC90No.RangeMIC90
L. acidophilus
 Penicillin70.125–2…
 Ampicillin70.5…
 Erythromycin70.06–4…
 Clindamycin70.06–0.25…
 Vancomycin70.125–0.5…
 Ciprofloxacin72–16…
 Bacitracin70.5–2…
 Chloramphenicol70.25–4…
 Tetracycline70.5–2…
 Gentamicin72–64…
L. casei
 Penicillin70.5–2…120.25–4251–2…
 Ampicillin71–4…120.5–4250.125–1…
 Cefuroxime122–>25664
 Ceftriaxone88–>64…128–>256>256
 Cefoxitin7>128…
 Piperacillin-tazobactam90.5–8…120.5–84
 Ertapenem5>16…
 Imipenem90.25–8…120.5–22
 Erythromycin12≤0.03–0.250.1250.06–0.5…
 Clindamycin80.06–0.5…120.06–0.250.2550.5…
 Vancomycin7>64…12>256>2565>256…
 Ciprofloxacin120.5–4158–32…
 Bacitracin50.5–4…
 Chloramphenicol50.25–2…
 Daptomycin71–4…
 Linezolid54…
 Doxycycline120.25–11
 Tetracycline50.5–1…
 Gentamicin54–128…
 Netilmicin120.12–44
 Tobramucin120.5–1616
L. delbrueckii ssp. bulgaricus
 Penicillin10.125130.06.–0.250.25
 Ampicillin10.125130.125–0.250.25
 Cefoxitin116
 Piperacillin-tazobactam10.25
 Imipenem10.125
 Ertapenem10.5
 Erythromycin130.06–0.50.5
 Clindamycin1≤0.03130.06–0.50.5
 Vancomycin10.5130.125–0.50.5
 Daptomycin10.5
 Ciprofloxacin132–3232
 Levofloxacin10.5
 Bacitracin130.05–22
 Chloramphenicol130.25––162
 Tetracycline130.125–22
 Gentamicin134–6464
L. fermentum
 Penicillin30.25–0.5…120.25–0.50.2550.125–0.5…
 Ampicillin30.125–0.25…120.12–0.250.2550.125–0.5…
 Cefuroxime120.25–168
 Ceftriaxone116…120.5–>25632
 Cefoxitin2>128…
 Piperacillin-tazobactam50.5–2…121–21
 Imipenem5≤0.015–0.5…12≤0.03–10.06
 Ertapenem20.5–1…
 Erythromycin12≤0.03–0.250.1250.125–>64…
 Clindamycin3≤0.03…12≤0.06–0.250.0650.125–>64…
 Vancomycin532–>32…12>256>2565>256>256
 Daptomycin30.25…
 Linezolid24…
 Ciprofloxacin124–323254–8…
 Levofloxacin14…
 Bacitracin52–4…
 Chloramphenicol50.25–8…
 Doxycycline120.5–44
 Tetracycline50.125–4…
 Gentamicin54–128…
 Netilmicin120.06–20.25
 Tobramycin120.5–84
L. parabuchnerii
 Penicillin120.06–0.250.25
 Ampicillin120.125–0.50.5
 Erythromycin120.06–0.50.125
 Clindamycin120.06–0.50.125
 Vancomycin120.125–0.50.5
 Ciprofloxacin124–3232
 Bacitracin120.125–22
 Chloramphenicol120.25–162
 Tetracycline128–3232
 Gentamicin121–128128
L. plantarum
 Penicillin1>32…18…70.125–1…
 Ampicillin2…10.5…70.125–0.5…
 Cefuroxime12…
 Ceftriazone11…
 Piperacillin-tazobactam11…
 Erythromycin70.06–32…
 Clindamycin10.5…12…70.06–0.125…
 Vancomycin1>32…1>256…7>256…
 Imipenem1≤0.06…1≤0.03…
 Ertapenem14…
 Ciprofloxacin1>32…72–32…
 Bacitracin70.5–8…
 Chloramphenicol70.25–2…
 Tetracycline71–>128…
 Gentamicin74–128…
 Netilmycin11…
 Tobramycin18…
L. rhamnosus GG
 Penicillin220.25–21
 Ampicillin220.5–21
 Cefuroxime222–168
 Ceftriaxone22128–>256>256
 Piperacillin-tazobactam221–21
 Imipenem220.5–22
 Erythromycin220.06–0.250.25
 Clindamycin220.06–0.50.25
 Vancomycin22>256>256
 Ciprofloxacin220.25–11
 Doxycycline220.25–10.5
 Netilmicin222–44
 Tobramycin224–3216
L. rhamnosus, not GG*
 Penicillin70.25–4…240.12–4441–2…
 Ampicillin81–4…240.25–8240.5–1…
 Cefuroxime242–128128
 Ceftriaxone916–64…242–>256>256
 Cefoxitin7>128…
 Piperacillin-tazobactam151–84240.5–84
 Imipenem152–168240.25–44
 Ertapenem516–>16…
 Erythromycin24≤0.03–0.250.2540.06–0.5…
 Clindamycin110.06–11240.06–0.50.540.06–0.5…
 Vancomycin10>32>3224>256>2574>256…
 Daptomycin81–4…
 Linezolid52–4…
 Ciprofloxacin240.25–2144–32…
 Levofloxacin31–2…
 Bacitracin40.5–4…
 Chloramphenicol40.25–2…
 Doxycycline240.25–0.50.5
 Tetracycline41–4…
 Gentamicin432–128…
 Netilmicin240.5–44
 Tobramycin242–3216
L. salivarius
 Penicillin20.125–0.2530.12–0.25…50.125–>64…
 Ampicillin20.25–0.530.12–0.25…50.125–0.25…
 Cefuroxime30.25–0.5…
 Ceftriaxone1130.5–1…
 Cefoxitin116
 Piperacillin-tazobactam1131…
 Imipenem20.03–0.1253≤0.03–0.5…
 Ertapenam21
 Erythromycin30.06–0.25…50.06–>64…
 Clindamycin20.25–0.53≤0.03–0.25…50.06–0.5…
 Vancomycin2>323>256…5>256…
 Linezolid11
 Ciprofloxacin30.5–1…54–32…
 Levofloxacin11
 Bacitracin52–8…
 Chloramphenicol50.25–32…
 Doxycycline30.25–1…
 Tetracycline5>128…
 Gentamicin516–128…
 Netilmicin30.25–4…
 Tobramycin31–32…
Species/Drug [no. isolates]Goldstein [38–42]
Salminen [8]
Nawaz [36]
No.RangeMIC90No.RangeMIC90No.RangeMIC90
L. acidophilus
 Penicillin70.125–2…
 Ampicillin70.5…
 Erythromycin70.06–4…
 Clindamycin70.06–0.25…
 Vancomycin70.125–0.5…
 Ciprofloxacin72–16…
 Bacitracin70.5–2…
 Chloramphenicol70.25–4…
 Tetracycline70.5–2…
 Gentamicin72–64…
L. casei
 Penicillin70.5–2…120.25–4251–2…
 Ampicillin71–4…120.5–4250.125–1…
 Cefuroxime122–>25664
 Ceftriaxone88–>64…128–>256>256
 Cefoxitin7>128…
 Piperacillin-tazobactam90.5–8…120.5–84
 Ertapenem5>16…
 Imipenem90.25–8…120.5–22
 Erythromycin12≤0.03–0.250.1250.06–0.5…
 Clindamycin80.06–0.5…120.06–0.250.2550.5…
 Vancomycin7>64…12>256>2565>256…
 Ciprofloxacin120.5–4158–32…
 Bacitracin50.5–4…
 Chloramphenicol50.25–2…
 Daptomycin71–4…
 Linezolid54…
 Doxycycline120.25–11
 Tetracycline50.5–1…
 Gentamicin54–128…
 Netilmicin120.12–44
 Tobramucin120.5–1616
L. delbrueckii ssp. bulgaricus
 Penicillin10.125130.06.–0.250.25
 Ampicillin10.125130.125–0.250.25
 Cefoxitin116
 Piperacillin-tazobactam10.25
 Imipenem10.125
 Ertapenem10.5
 Erythromycin130.06–0.50.5
 Clindamycin1≤0.03130.06–0.50.5
 Vancomycin10.5130.125–0.50.5
 Daptomycin10.5
 Ciprofloxacin132–3232
 Levofloxacin10.5
 Bacitracin130.05–22
 Chloramphenicol130.25––162
 Tetracycline130.125–22
 Gentamicin134–6464
L. fermentum
 Penicillin30.25–0.5…120.25–0.50.2550.125–0.5…
 Ampicillin30.125–0.25…120.12–0.250.2550.125–0.5…
 Cefuroxime120.25–168
 Ceftriaxone116…120.5–>25632
 Cefoxitin2>128…
 Piperacillin-tazobactam50.5–2…121–21
 Imipenem5≤0.015–0.5…12≤0.03–10.06
 Ertapenem20.5–1…
 Erythromycin12≤0.03–0.250.1250.125–>64…
 Clindamycin3≤0.03…12≤0.06–0.250.0650.125–>64…
 Vancomycin532–>32…12>256>2565>256>256
 Daptomycin30.25…
 Linezolid24…
 Ciprofloxacin124–323254–8…
 Levofloxacin14…
 Bacitracin52–4…
 Chloramphenicol50.25–8…
 Doxycycline120.5–44
 Tetracycline50.125–4…
 Gentamicin54–128…
 Netilmicin120.06–20.25
 Tobramycin120.5–84
L. parabuchnerii
 Penicillin120.06–0.250.25
 Ampicillin120.125–0.50.5
 Erythromycin120.06–0.50.125
 Clindamycin120.06–0.50.125
 Vancomycin120.125–0.50.5
 Ciprofloxacin124–3232
 Bacitracin120.125–22
 Chloramphenicol120.25–162
 Tetracycline128–3232
 Gentamicin121–128128
L. plantarum
 Penicillin1>32…18…70.125–1…
 Ampicillin2…10.5…70.125–0.5…
 Cefuroxime12…
 Ceftriazone11…
 Piperacillin-tazobactam11…
 Erythromycin70.06–32…
 Clindamycin10.5…12…70.06–0.125…
 Vancomycin1>32…1>256…7>256…
 Imipenem1≤0.06…1≤0.03…
 Ertapenem14…
 Ciprofloxacin1>32…72–32…
 Bacitracin70.5–8…
 Chloramphenicol70.25–2…
 Tetracycline71–>128…
 Gentamicin74–128…
 Netilmycin11…
 Tobramycin18…
L. rhamnosus GG
 Penicillin220.25–21
 Ampicillin220.5–21
 Cefuroxime222–168
 Ceftriaxone22128–>256>256
 Piperacillin-tazobactam221–21
 Imipenem220.5–22
 Erythromycin220.06–0.250.25
 Clindamycin220.06–0.50.25
 Vancomycin22>256>256
 Ciprofloxacin220.25–11
 Doxycycline220.25–10.5
 Netilmicin222–44
 Tobramycin224–3216
L. rhamnosus, not GG*
 Penicillin70.25–4…240.12–4441–2…
 Ampicillin81–4…240.25–8240.5–1…
 Cefuroxime242–128128
 Ceftriaxone916–64…242–>256>256
 Cefoxitin7>128…
 Piperacillin-tazobactam151–84240.5–84
 Imipenem152–168240.25–44
 Ertapenem516–>16…
 Erythromycin24≤0.03–0.250.2540.06–0.5…
 Clindamycin110.06–11240.06–0.50.540.06–0.5…
 Vancomycin10>32>3224>256>2574>256…
 Daptomycin81–4…
 Linezolid52–4…
 Ciprofloxacin240.25–2144–32…
 Levofloxacin31–2…
 Bacitracin40.5–4…
 Chloramphenicol40.25–2…
 Doxycycline240.25–0.50.5
 Tetracycline41–4…
 Gentamicin432–128…
 Netilmicin240.5–44
 Tobramycin242–3216
L. salivarius
 Penicillin20.125–0.2530.12–0.25…50.125–>64…
 Ampicillin20.25–0.530.12–0.25…50.125–0.25…
 Cefuroxime30.25–0.5…
 Ceftriaxone1130.5–1…
 Cefoxitin116
 Piperacillin-tazobactam1131…
 Imipenem20.03–0.1253≤0.03–0.5…
 Ertapenam21
 Erythromycin30.06–0.25…50.06–>64…
 Clindamycin20.25–0.53≤0.03–0.25…50.06–0.5…
 Vancomycin2>323>256…5>256…
 Linezolid11
 Ciprofloxacin30.5–1…54–32…
 Levofloxacin11
 Bacitracin52–8…
 Chloramphenicol50.25–32…
 Doxycycline30.25–1…
 Tetracycline5>128…
 Gentamicin516–128…
 Netilmicin30.25–4…
 Tobramycin31–32…

Abbreviation: MIC, minimum inhibitory concentration.

a Goldstein, agar dilution, Clinical Laboratory Standards Institute; Salminen, Etest; Nawaz, International Organization of Standardization/International Dairy Federation.

It is well known that susceptibility results are affected by medium composition, inoculum and atmosphere of incubation, and time of incubation. To complicate the issue, the Clinical Laboratory Standards Institute (CLSI) and the International Organization of Standardization/International Dairy Federation (ISO/IDF) have published and promulgated different methods for antimicrobial susceptibility testing. The focus of CLSI is clinical isolates from human infections, whereas the Dairy Federation is focused on species or strains not typically associated with clinical infections.

The CLSI M45-A2 document recommended cation-adjusted Mueller-Hinton broth supplemented with 5% lysed horse blood with incubation in an augmented CO2 atmosphere at 37°C for 24–48 hours [43]. Tables for interpretation of MICs are included in this document. In our laboratory, we have often tested lactobacilli by the CLSI anaerobic agar dilution testing methods (CLSI M11-A8) [44] using Brucella blood agar supplemented with hemin and vitamin K1with incubation under anaerobic conditions. Some isolates, especially the vaginal isolates of L. crispatus, and L. iners are best grown in an anaerobic environment (Citron, personal observation).

In 2008, using lactic acid bacteria susceptibility medium based media developed by the ISO/IDF, Mayrhofer et al [45] compared the broth microdilution, Etest, and agar disk diffusion methods against 104 strains of the L. acidophilus group. They found that compared to broth microdilution tests, Etest MICS were lower for ampicillin, clindamycin, erythromycin, and streptomycin, whereas they are conversely higher for vancomycin and gentamicin. They also reported MIC variations with tetracycline when tested by the broth method. However, they concluded that disk diffusion results “correlated well with the MICs from Etest and broth microdilution” methods.

CONCLUSION

Lactobacillus species are taxonomically complex, and the paucity of data make it difficult to generalize about the genus. Lactobacilli survive in an acid pH as in the stomach, and many of the probiotic type strains are both metronidazole and vancomycin resistant suggesting that they should survive with some concurrent treatments. However, many of the species are susceptible to penicillin and ampicillin; therefore, caution is advised. Further research and study are required to characterize their taxonomy, in vitro susceptibilities and their roles in health and disease.

Notes

Supplement sponsorship. This article appeared as part of the supplement “Probiotics: Added Supplementary Value in Clostridium difficile Infection,” sponsored by Bio-K Plus International.

Potential conflicts of interest. E. J. C. G. is a member of the Bio K+ Scientific Advisory Board. All other authors report no potential conflicts.

All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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