Bacteria Associated with Intrinsic Antibiotic Resistance

Generally, when people (either the general public or a physician or laboratory personnel) listen/read the term “antibiotic resistance” they may think, ‘a bacterium which was previously sensitive to a particular antibacterial agent has now developed resistance against it (either through the acquisition of gene via horizontal gene transfer or by mutation)’ but in this universe, there are innumerable species of bacteria which are innately resistant to particular drugs.

According to CLSI, “Intrinsic resistance is so common that susceptibility testing is unnecessary. For example, Citrobacter species are intrinsically resistant to ampicillin”.

Intrinsic antibiotic resistance is a naturally occurring phenomenon independent of previous antibiotic exposure and is not caused by a horizontal gene transfer. Remember the famous example of intrinsic resistance, penicillin not working against Mycoplasma. Penicillin kills bacteria by interfering with their cell wall synthesis.

Will it be able to kill those that do not have a cell wall?

Intrinsic antibiotic resistance is mainly mediated by the impermeability of cellular envelopes, the activity of multidrug efflux pumps, or the lack of drug targets. Enzymes (such as transferases) involved in basic bacterial metabolic processes also confer intrinsic resistance in some bacterial species such as Pseudomonas aeruginosa, and Staphylococcus aureus.

According to the published findings, such natural insensitivity can be due to:

• lack of affinity of the drug for the bacterial target
• inaccessibility of the drug into the bacterial cell
• extrusion of the drug by chromosomally encoded active exporters
• innate production of enzymes that inactivate the drug

Intrinsic Antibiotic Resistance in Gram-Negative Bacteria

Bacterial pathogens that are Intrinsically resistant to Ampicillin are:

1. Acinetobacter baumanni complex
2. Citrobacter freundii
3. Citrobacter koseri
4. Klebsiella (formerly Enterobacter) aerogenes
5. Enterobacter cloacae complex
6. Klebsiella pneumoniae
7. Morganella morganii
8. Proteus vulgaris
9. Pseudomonas aeruginosa
10. Serratia marcescens
11. Yersinia enterocolitica

Bacterial pathogens that are Intrinsically Resistant to Amoxicillin-Clavulanate combination

1. Citrobacter freundii
2. Klebsiella (formerly Enterobacter) aerogenes
3. Enterobacter cloacae complex
4. Morganella morganii
5. Pseudomonas aeruginosa
6. Serratia marcescens
7. Yersinia enterocolitica
8. Burkholderia cepacia complex
9. Stenotrophomonas maltophilia

Bacterial pathogens that are Intrinsically Resistant to Ampicillin-sulbactam combination

1. Citrobacter freundii
2. Citrobacter koseri
3. Klebsiella (formerly Enterobacter) aerogenes
4. Enterobacter cloacae complex
5. Proteus vulgaris
6. Pseudomonas aeruginosa
7. Serratia marcescens

Citrobacter koseri is intrinsically resistant to piperacillin, whereas Proteus spp is intrinsically resistant to tetracycline/tigecycline, nitrofurantoin and polymyxin B, and colistin.

Serratia marcescens

Serratia marcescens is resistant to the following drugs.

1. Ampicillin
2. Amoxicillin-clavulanate
3. Ampicillin-sulbactam
4. Cephalosporins I: Cefazolin, Cephalothin
5. Cephamycins: Cefoxitin, Cefotetan
6. Cephalosporin II: Cefuroxime
7. Nitrofurantoin
8. Polymyxin B, Colisin

Yersinia enterocolitica

Yersinia enterocolita is resistant to the following drugs;

1. Ampicillin, Amoxicillin
2. Amoxicillin-Clavulanate
3. Ticarcillin
4. Cephalosporins I: Cefazolin, Cephalothin

Acinetobacter baumanni complex is a notorious pathogen that is resistant to most of the available antibiotics. It is intrinsically resistant to

1. Ampicillin, Amoxicillin
2. Amoxicillin-Clavulanate
3. Aztreonam
4. Ertapenem
5. Trimethoprim
6. Chloramphenicol
7. Fosfomycin

Similarly, Pseudomonas aeruginosa is intrinsically resistant to

1. Ampicillin, Amoxicillin
2. Ampicillin-sulbactam
3. Amoxicillin-Clavulanate
4. Cefotaxime
5. Ceftriaxone
6. Ertapenem
7. Tetracyclines/Tigecyclines
8. Trimethoprim
9. Trimethoprim-sulfamethoxazole
10. Chloramphenicol

Both Acinetobacter and Pseudomonas are also intrinsically resistant to penicillin (ie, benzylpenicillin), cephalosporin I (cephalothin, cefazolin), cephalosporin II (cefuroxime), cephamycins (cefoxitin, cefotetan), clindamycin, daptomycin, fusidic acid, glycopeptides(vancomycin, teicoplanin), linezolid, macrolides (erythromycin, azithromycin, clarithromycin), quinupristin-dalfopristin, and rifampin.

Bacteroides spp. which is one of the most frequently isolated anaerobic Gram-negative bacilli is intrinsically resistant to

• Aminoglycosides
• Penicillin and
• Ampicillin

Intrinsic Antibiotic Resistance in Gram-positive Bacteria

Among Gram-positive bacteria, S. saprophyticus is intrinsically resistant to novobiocin which is the basis for novobiocin sensitivity test done in urine isolate (if CONS is isolated).

Enterococcus faecalis/faecium are intrinsically resistant to

• Cephalosporin*
• Aminoglycosides*
• Clindamycin*
• Trimethoprim
• Trimethoprim-sulfamethoxazole*
• Fusidic acid
  *may appear active in vitro but are not effective clinically and should not be reported as susceptible.

Both Enterococci and Staphylococci are also intrinsically resistant to aztreonam, polymyxin B/colistin, and nalidixic acid.

Anaerobic Gram-positive bacilli, Clostridium spp. is resistant to aminoglycosides.

References and further reading 

1. CLSI: M100S: Performance Standards for Antimicrobial Susceptibility Testing