Pediococci
Authors: William Riebel, M.D.
Microbiology
Pediococci are well-studied organisms known primarily for their spoilage-retarding, but also spoilage-producing properties, in the food industries. Their intrinsic vancomycin resistance led to their recognition in clinical microbiology in the late 1980's, having been previously confused with oral streptococci and enterococci (8,13,31).Pediococci are catalase-negative, gram-positive cocci, arranged in pairs and tetrads, whose colony morphologies resemble oral streptococci on blood agar. The only two species clinically isolated at this time are Pediococcus acidilactici and Pediococcus pentosaceus. Other recognized species are P. damnosus , P. dextrinicus , and P. parvulus , with the prior identifications of P. urinae-equi reassigned as Aerococcus viridans , P. halophilus renamed as Tetragenococcus halophilus , and P. cerevisiae being reassigned to P. acidilactici (4).
Epidemiology
Since pediococci are often found in foods, it is not surprising that they have been recognized as a part of both mouth and fecal flora (2,26,32,34,38). Areas from or near the gastrointestinal tract, or skin surfaces possibly contaminated with fecal flora, are the most common sites from which they have been clinically isolated. Prior vancomycin usage has been associated with increased stool recovery (26,38), as well as isolation associated with infections (1,5,9,18,25, 35).
Pediococci have been found in many clinical populations, including children (1,5,25), and pregnant women (29,33). Isolates have been found worldwide: from the United States (1,5,20,26,36), from Europe (8,9,18,26,38), Bernabeu, Heinz, Michalopoulos, Vento), from South America (4), from Southeast Asia (21,29), from Australia (16), and from India (33).
Clinical Manifestations
Reported infections arising from areas near the gastrointestinal tract include abdominal wall abscesses (27,31), intra-abdominal abscesses and fluid from ruptured bowel (27,31,35), and enterocutaneous fistulae (15,31). Although most blood culture isolates have arisen from unclear sources (5,9,14,18,25,33,35,38), many bacteremic patients have had gastrointestinal surgeries for perforations (1,5,9,14,18,25,27,35,36). Blood culture isolates from patients thought to have endocarditis have been reported (14,20,41).Some bacteremic isolates have been reported to arise from central venous catheters (1,16), although other bacteremias may have been line-related. Urine isolates have been reported, as have isolates from cyst material, lung, and bone (14). Isolates have been reported from CSF (14) and one strain appears to have caused meningitis (5).
Laboratory Diagnosis
Pediococci have been clinically isolated by conventional microbiologic cultures using standard media, although selective media can been used (34). Several papers have been written on conventional identification methods (4,15,24), but the combination of vancomycin resistance and tetrading morphology from growth in broth media in isolates that superficially resemble oral streptococci on blood agar suggests their species identification (13,31). More elaborate methods are required occasionally for speciation (4).
Pathogenesis
P. acidilactici has been reported relatively more frequently than P. pentosaceus from clinical sites (23 vs. 3 isolates in this review) in comparison to stool (105 vs. 26 isolates), which may suggest that P. acidilactici is the slightly more virulent organism of the two. However, there appears to be no particular disease process typical to either of the two species of pediococci clinically isolated. Overall, pediococci seem to be of limited clinical importance, but with only recent clinical recognition, information concerning their pathogenicity is still being gathered. In general, evidence suggests a pathogenic potential similar to, but probably less than, oral streptococci.
SUSCEPTIBILITY IN VITRO AND IN VIVO
Single Drug
Similar in vitro susceptibility results have been noted both by agar dilution using Müller-Hinton agar supplemented with 5% horse serum (26,38) and by broth microdilution using cation-supplemented Müller-Hinton broth with 5% lysed blood of different types (37); results from these methods are similar and are commented upon below. Slightly higher microdilution MIC's were occasionally found by using cation-supplemented Müller-Hinton broth without blood supplementation (42). Sensitivity testing by disc diffusion showed poor correlation to agar dilution and broth microdilution (37,38), although general agreement was noted elsewhere (42). Etest sensitivities correlated well with broth microdilution (19).
The sensitivity results of Tankovic are shown in (Table 1) and are fairly representative of most studies (38). In general the sensitivity profile of pediococci resembles the profile of enterococci, which undoubtedly has contributed to the identification confusion between these two species (31).
Among the beta-lactam type antimicrobials penicillin has shown an MIC90of less than or equal to 1 µg/ml, and a few isolates of pediococci have been susceptible at the non-enterococcal break point concentration of 0.12 µg/ml (11,22,38,43). Because of this, some authors have labeled their strains as penicillin-resistant (5,9,18), although beta-lactam therapy has been successful in all reported occasions save one (20).
Among the penicillins, amoxicillin and piperacillin have remained reasonably active, with the extended spectrum penicillins like piperacillin being less active (38). Among the beta-lactam-like agents, imipenem has proven very active in vitro, with MIC90generally less than or equal to 0.12 µg/ml (38,40).Cephalosporins have shown poor activity (11,38).
Macrolides and lincosomides have been particularly active, with an erythromycin and clindamycin MIC90's of 0.06-0.12 µg/ml and 0.015-0.15 µg/ml respectively (11,22,38).Occasional strains have shown high level macrolide resistance, however (37, 38,42,43). A strain of P. acidilactici highly resistant to macrolides was shown to be inducibly resistant to MLS antibiotics, mediated by a 46-b non-conjugative plasmid (38). Pediococci are known to host numerous plasmids encoding for antibiotic resistance, bacteriocin production, and carbohydrate fermentation changes.
Some of the agents active against gram positive bacteria show in vitro activity against pediococci.Rifampin and chloramphenicol have shown moderate susceptibility with MIC90of 2 -4 µg/ml (10,38,40).Quinopristin/dalfopristin activity has been variable (3,22,23,43), as has been the activity of linezolid (10,19,22).
Daptomycin has shown excellent in vitro activity against pediococci (7,11,19), and since daptomycin has been usually bactericidal against gram positive bacteria, its use has been recommended ( 20,36).However, tests of bactericidal activity have not been reported.
Several antimicrobials have shown poor activity against pediococci, in addition to vancomycin.Aminoglycosides have been inactive, although gentamicin has been more active than other aminoglycosides ( 38 ). Tetracyclines have been poorly active (MIC90= 32 -64 µg/ml), although minocycline and doxycycline have been 2 dilutions more active generally (22,38). Ciprofloxacin and other quinolones have been poorly active with MIC90= 16 -32 µg/ml (10,22,38,40).Pediococci are intrinsically resistant to trimethoprim, and are universally resistant to trimethoprim-sulfamethoxisole (22,38,40).
Theintrinsic vancomycin resistance that is characteristic of pediococci is due to the amino acid termination of d-Ala, d-Lac in the peptidoglycan cell wall precursors, which differs from the transferable resistance found in clinical isolates of enterococci (30). Teichoplanin is also inactive (28,38).
Combination Therapy
Time killcurves for penicillin and imipenem against two strains of pediococci showed only a one to two log10reduction in bacterial counts after 24 hours incubation, implying that neither agent was bactericidal (38). There has been no in vitro or in vivo synergy data reported for pediococci.
ANTIMICROBIAL THERAPY
General Drug of Choice
Since it has been difficult to determine the clinical significance of pediococcal isolates, it has been difficult to determine the optimal therapy for infections due to these organisms.Penicillin or penicillin derivatives, with or without aminoglycosides, have been used most frequently, with apparent success in bacteremias (5,9,16,25,33). Beta-lactam beta-lactamase combinations, such as piperacillin-tazobactam and ampicillin-sulbactam, have been successful in various infections (6,25,29), although beta-lactamase inhibitors provide no increased activity in vitro. Imipenem (18,35) and clindamycin (1,18) have been used with success. There have been no reports of erythromycin or erythromycin analogue use, despite good in vitro activity. Daptomycin has been successful in cases of endocarditis (20) and ascending cholangitis (36). From this limited clinical information, daptomycin would seem to be the drug of choice when bactericidal activity is desired.Penicillin or it derivatives or combinations would seem adequate when bactericidal activity is not necessary.
Special Situations
Gastrointestinal Perforations
When found in wound or intraabdominal fluid cultures associated with gastrointestinal perforations, pediococci have generally been a part of a mixed bacterial flora which usually has included recognized pathogens; there has been no suggestion that antimicrobial therapy needs to be directed at pediococci in these situations (31). One case of P. acidilactici bacteremia occurred at the same time as a polymicrobial bile and intraabdominal abscess infection, which included P. acidilactici (35).One case of pure P. pentosaceus bacteremia and necrotizing fasciitis of the abdominal wall, presumptively due to peritonitis due to colon perforation due to a perforating tumor was described (27). A Pediococcus sp. was found in pure culture in a case of a liver abscess, which responded to drainage and 2 weeks of piperacillin-tazobactam followed by 2 weeks of oral ampicillin-sulbactam (6). Infection of a vaginal remnant (pyocolpos) due to a Pediococcus sp. responded to drainage and 7 days of ampicillin-sulbactam (29).Drainage of infected material, correction of the perforation, and antimicrobials directed at more recognized pathogens has been successful when achieved (1,5,6,9,18,25,29,31, 35).
Endocarditis
Although there have been cases of endocarditis reported (14, 20,41), one case report of endocarditis is instructive ( 20).This was a case of P. acidilactici bacteremia presumptively due to an infected central line in a TPN-dependent patient with short gut syndrome.A transesophageal echocardiogram (TEE) showed a mitral valve vegetation.A patent foramen ovale was present as were apparent septic pulmonary emboli.Bacteremia and fevers persisted for 7 days on piperacillin-tazobactam, with bacteremia and fevers resolving after daptomycin initiation.Daptomycin was used for 39 days with clinical and microbiological cure at 1 year follow-up (20).In a different case a Pediococcus species was isolated from a bioprosthetic heart valve removed from a patient with Bartonella quintana endocarditis; clinical and microbiologic cure was achieved with one month of piperacillin-tazobactam followed by 1 year of doxycycline (41).With the limited in vitro data suggesting that beta-lactams are not bactericidal against pediococci (38), and the suspicion that daptomycin may be bactericidal against pediococci, confirmed by one case report, daptomycin is probably the preferred agent in endocarditis.A combination ofpenicillin and an aminoglycoside could also be used, although there is no evidence that this combination is bactericidal either. In vitro measurement of the minimal bactericidal concentration (MBC) of the chosen antimicrobial regimen would be optimal.
Bacteremia and Intravascular Line Infections
Successful therapies have been described for bacteremias of various causes (1,5,6,9,18, 20,25, 35,36). Intravascular line infections have resolved without catheter removal (16), although bacteremia continued after catheter removal in one instance prior to active antimicrobial therapy (1). In many cases of bacteremia, central line usage was not described, although central lines were likely used.
Underlying Diseases
As mentioned above pediococci have been isolated from patients after gastrointestinal perforations or surgeries (1,5,6,9,18,25,27,31, 35,36), after use of enteral feedings (5,19), after long term antibiotic treatments (5,9,16,18,25,26,31, 35), after placement of central lines (1,5,16,20,25), after chemotherapy-induced leukopenia in marrow-related malignancies or organ transplantation (5,17,26), and after prolonged hospitalizations (1,5,6,9,16,18,25,26,31, 35,36,41). The specific risk of each of these related situations is unknown. Prior vancomycin use has been found frequently in reports of pediococcal isolation (5,9,16,17,18,25,26, 35,36). The fecal flora of volunteers given glycopeptides frequently shows emergence of pediococci (12,39).
Alternative Therapy
With usual excellent in vitro susceptibilities, either erythromycin or clindamycin would seem reasonable for the penicillin allergic patient, with clindamycin having been reported effective (1,18). Erythromycin resistance has been found in a minority of isolates; as yet, there have been not reported use of his drug to treat a patient with a pediococcal infection.Imipenem would be a good alternative agent to the penicillins (18, 35). In general, therapies other than penicillin or daptomycin would be best selected from in vitro data on the individual pediococcal isolate.
Combination Therapy
There is no reported information to support combination therapy in pediococcal infections.Si nce beta-lactam-type antimicrobials may be bacteriostatic against pediococci (38), the addition of an aminoglycoside to penicillin may be wise in clinical situations such as endocarditis, although there is as yet no proof that this combination is synergistic. Ampicillin and gentamicin combination therapy was successful in a case of apparent nosocomial meningitis (5).
VACCINES
There are no vaccines in use or in development against pediococci.
ENDPOINTS FOR MONITORING THERAPY
There are no special endpoints except to reculture the site of infection if clinical response is poor.
ADJUNCTIVE THERAPY
There are no specific adjunctive therapies.
PREVENTION
There are no special preventive measures.
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Tables
Table 1. MIC's (in µg/ml) of 28 Antimicrobial Agents for 36 Strains of Pediococcus spp (38).
| Range | MIC50 | MIC90 |
|---|---|---|---|
| Penicillin G | 0.25-1 | 0.5 | 0 5 |
| Amoxicillin | 0.25-2 | 1 | 1 |
| Ticarcillin | 4-32 | 16 | 16 |
| Piperacillin | 0.5-2 | 2 | |
| Imipenem | 0.03-0.12 | 0.12 | 0 12 |
| Cefaclor | 32-128 | 64 | 128 |
| Cefotaxime | 1-8 | 4 | 8 |
| Gentamicin | 0.25-2 | 1 | 1 |
| Netilmicin | 0.25-2 | 0.5 | 1 |
| Tobramycin | 2-32 | 4 | 32 |
| Amikacin | 2-32 | 4 | 16 |
| Erythromycin | 0.06>128 | 0.12 | 0 12 |
| Spiramycin | 0.12->128 | 0.5 | 0 5 |
| Lincomycin | 0.O6>128 | 0.5 | 1 |
| Clindamycin | <0.008-16 | 0.015 | 015 |
| Pristinamycin factor I | 1-16 | 4 | |
| Pristinamycin factor II | 16>128 | 64 | >128 |
| Pristinamycin | 0.25-2 | 0.25 | 1 |
| Tetracycline | 4-128 | 32 | 64 |
| Minocycline | 1-32 | 8 | 16 |
| Novobiocin | 0.5-128 | 1 | 64 |
| Vancomycin | 512->1,024 | >1,024 | >1,024 |
| Teicoplanin | 32->1,024 | >1024 | >1,024 |
| Daptomycin | 0.12-0.5 | 0.25 | 0.5 |
| Ramoplanin | 0.25-2 | 0.5 | |
| Rifampin | 0.5-8 | 2 | 4 |
| Chloramphenicol | 1-8 | 2 | 4 |
| Ciprofloxacin | 1-32 | 16 | 32 |
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