What antibiotics are effective against Proteus (Proteus) species?

From the Guidelines

Proteus species, particularly Proteus mirabilis, are typically sensitive to several antibiotics, including fluoroquinolones, third-generation cephalosporins, aminoglycosides, and trimethoprim-sulfamethoxazole. The most effective antibiotics against Proteus include:

• Fluoroquinolones (such as ciprofloxacin 500mg twice daily for 7-14 days) 1
• Third-generation cephalosporins (like ceftriaxone 1-2g daily) 1
• Aminoglycosides (gentamicin 5-7mg/kg/day) 1
• Trimethoprim-sulfamethoxazole (160/800mg twice daily for 7-14 days) 1 Carbapenems (meropenem 1g every 8 hours) are highly effective for resistant strains 1. Ampicillin or amoxicillin combined with beta-lactamase inhibitors (such as amoxicillin-clavulanate 875/125mg twice daily) can also be effective 1. However, Proteus species are naturally resistant to nitrofurantoin, tetracyclines, and colistin, so these should be avoided 1. The choice of antibiotic should be guided by susceptibility testing whenever possible, as resistance patterns can vary 1. Treatment duration typically ranges from 7-14 days depending on the infection site and severity, with longer courses needed for complicated infections 1. It is essential to note that the use of antibiotics should be based on the clinical condition of the patient, individual risk for infection by resistant pathogens, and local resistance epidemiology 1. In the context of intra-abdominal infections, the main resistance problem is posed by ESBL-producing Enterobacteriaceae, which are prevalent in hospital-acquired infections but observed in community-acquired infections as well 1. Therefore, the selection of empiric antibiotic therapy is critical for preventing unnecessary morbidity and mortality from intra-abdominal infections. In patients with uncomplicated intra-abdominal infections, such as uncomplicated appendicitis and uncomplicated cholecystitis, where the source of infection is treated definitively, post-operative antibiotic therapy is not necessary 1. However, in patients with complicated intra-abdominal infections undergoing an adequate source-control procedure, a short course of antibiotic therapy (3-5 days) is always recommended 1. Patients who have ongoing signs of peritonitis or systemic illness beyond 5 to 7 days of antibiotic treatment normally warrant a diagnostic investigation to determine whether additional surgical intervention is necessary to address an ongoing uncontrolled source of infection or antimicrobial treatment failure 1. The prolonged and inappropriate use of antibiotics appears to be a key factor in the rapid rise of antimicrobial resistance worldwide over the past decade 1. A rational and appropriate use of antibiotics is particularly important both to optimize quality clinical care and to reduce selection pressure on resistant pathogens 1. Several strategies aiming at achieving optimal use of antimicrobial agents have been described, but it is essential that clinicians know antibiotic administration minimal requirements 1. Without these minimal requirements, clinicians worldwide will increase the likelihood of treatment failures and antibiotic resistance 1. The choice of empiric antibiotic regimens in patients with intra-abdominal infections should be based on the clinical condition of the patients, the individual risk for infection by resistant pathogens, and the local resistance epidemiology 1. Intra-abdominal infections may be managed with either single or multiple antibiotic regimens 1. Beta-lactam/beta-lactamase inhibitor combinations have an in vitro activity against gram-positive, gram-negative, and anaerobe organisms 1. Amoxicillin/clavulanate is still an option in mild community-acquired intra-abdominal infections 1. Broad-spectrum activity of piperacillin/tazobactam, including anti-Pseudomonas effect and anaerobic coverage, still makes it an interesting option for management of severe intra-abdominal infections 1. However, the use of piperacillin/tazobactam in patients with ESBL infections is still controversial 1, even if in stable patients, it may be still a therapeutic chance 1. Third-generation cephalosporins, including cefotaxime and ceftriaxone, in association with metronidazole, may be still options for the treatment of mild intra-abdominal infections 1. Ceftazidime and cefoperazone are third-generation cephalosporins with an activity against Pseudomonas aeruginosa 1. Cefepime, a fourth-generation cephalosporin, with broader spectrum activity than third-generation cephalosporins and effective against AmpC-producing organisms, should also be combined with metronidazole because it does not possess anti-anaerobic activity 1. Ciprofloxacin and levofloxacin are no longer appropriate choices as first-line treatment in many geographic regions because of the prevalence of fluoroquinolone resistance 1. However, when employed, these drugs should be used in association with metronidazole 1. In many current practices, the fluoroquinolones remain available for patients presenting allergy to beta-lactams, with mild intra-abdominal infections 1. Carbapenems offer a wide spectrum of antimicrobial activity against gram-positive and gram-negative aerobic and anaerobic pathogens (with the exception of MDR-resistant gram-positive cocci) 1. Group 1 carbapenems include ertapenem, which has activity against extended-spectrum beta-lactamase (ESBL)-producing pathogens, but not active against Pseudomonas aeruginosa and Enterococcus species 1. Group 2 includes imipenem/cilastatin, meropenem, and doripenem, which share activity against non-fermentative gram-negative bacilli 1. For more than two decades, carbapenems have been considered the agents of choice for multidrug-resistant infections caused by Enterobacteriaceae 1. The recent and rapid spread of K. pneumoniae carbapenem-resistant has become a critical issue in hospitals worldwide 1. The use of carbapenems should be limited so as to preserve activity of this class of antibiotics because of the concern of emerging carbapenem-resistance 1. Other options include aminoglycosides, particularly for suspected infections by gram-negative bacteria 1. They are effective against Pseudomonas aeruginosa, but are ineffective against anaerobic bacteria and need association with metronidazole 1. Because of their toxic side effects, some guidelines did not recommend aminoglycosides for the routine empiric treatment of community-acquired intra-abdominal infections, reserving them for patients with allergies to beta-lactam agents or in combination with beta-lactams for treatment of intra-abdominal infections with suspected MDR gram-negative bacteria 1. Tigecycline is a viable treatment option, especially in empiric therapy, for complicated intra-abdominal infections due to its favorable in vitro activity against anaerobic organisms, enterococci, several ESBL- and in association carbapenemase-producing Enterobacteriaceae, Acinetobacter species, and Stenotrophomonas maltophilia 1. It does not feature in vitro activity against Pseudomonas aeruginosa or Pseudomonas mirabilis 1. Caution is always advised for its use in suspected bacteremia and healthcare-associated pneumonia 1. The recent challenges of treating multidrug-resistant gram-negative infections, especially in critically ill patients, have renewed interest in the use of “old” antibiotics such as polymyxins and fosfomycin 1, now routinely used for treatment of MDR bacteria in critically ill patients. Ceftolozane/tazobactam and ceftazidime/avibactam are new antibiotics that have been approved for treatment of complicated intra-abdominal infections (in combination with metronidazole) including infection by ESBLs producing Enterobacteriaceae and Pseudomonas aeruginosa 1. These antimicrobials will be valuable for treating infections caused by MDR gram-negative bacteria in order to preserve carbapenems 1. Ceftolozane/tazobactam has excellent in vitro activity against MDR Pseudomonas aeruginosa 1. Ceftazidime/avibactam seems to have an in vitro activity against K. pneumoniae carbapenemase-producing bacteria 1. Although many reviews have been written, their precise role as empiric treatment for complicated intra-abdominal infections remains to be defined 1.

From the FDA Drug Label

Tobramycin has been shown to be active against most isolates of the following bacteria both in vitro and in clinical infections: Gram-positive bacteria Staphylococcus aureus Gram-negative bacteria Citrobacter species Enterobacter species Escherichia coli Klebsiella species Morganella morganii Pseudomonas aeruginosa Proteus mirabilis Proteus vulgaris Providencia species Serratia species

The antibiotics sensitive to Proteus are:

• Tobramycin 2
• Ceftazidime 3 Key points:
• Proteus mirabilis and Proteus vulgaris are sensitive to both tobramycin and ceftazidime.
• Both tobramycin and ceftazidime have been shown to be active against Proteus species in vitro and in clinical infections.

From the Research

Antibiotics Sensitive to Proteus

• Amikacin is effective against most gram-negative bacteria, including Proteus, and is considered the aminoglycoside of choice for treating serious gram-negative infections 4, 5, 6.
• Carbapenems, such as ertapenem, meropenem, and doripenem, are also effective against Proteus mirabilis, with all available isolates being susceptible to these antibiotics 7.
• Piperacillin/tazobactam is effective against Proteus mirabilis, with 95.6% of isolates being susceptible, but its effectiveness may depend on the MIC of the isolate 7.
• Gentamicin and tobramycin may not be effective against all Proteus strains, as some may be resistant to these antibiotics 4, 6.

Specific Studies

• A study from 1974 found that amikacin was effective in treating urinary tract infections caused by multiple-drug resistant Proteus rettgeri strains 5.
• A study from 2014 found that carbapenems and piperacillin/tazobactam were effective in treating bacteremia caused by extended-spectrum β-lactamase-producing Proteus mirabilis 7.
• A study from 2014 also found that the consumption of antibiotics, including amikacin and piperacillin/tazobactam, was associated with an increase in resistance to these antibiotics in Enterobacteriaceae, including Proteus mirabilis 8.