P. aeruginosa is a gram-negative bacteria which is widely distributed in nature. It’s a non-fastidious organism that has been isolated from sewage, distilled water, swimming pools, disinfectants, water baths, hot tubs, intravenous tubes and medical devices [1] . P. aeruginosa an opportunistic pathogen causes nosocomial infections and outbreaks with high mortality rates [2] [3] [4] . It rarely causes infection in healthy subjects but causes infection in the immunocompromised, burns patients, and organ transplant recipients and where there is disruption of physical barriers such as in the use of invasive devices [1] [5] . Most pathogens that cause nosocomial infections exhibit resistance to antimicrobial agents. Unfortunately, selection of the right drug is complicated by the organism’s ability to develop resistance to available classes of drugs even during treatment. Choice of treatment for Pseudomonas infection is limited. Drugs used for treatment include: beta lactams, aminoglycosides, fluoroquinolones with ciprofloxacin being the most active, and polymyxins (polymyxin B and colistin whose use is restricted to multi drug resistant P. aeruginosa (MDRPA) due to toxicity) [6] . P. aeruginosa is a multidrug resistant (MDR) organism and has several resistance mechanisms which include; chromosomal AmpC cephalosporinase depression, loss of permeability of the outer membrane (loss of OprD proteins), over expression of active efflux pumps, amino glycoside modifying enzymes synthesis, structural alterations of top oisomerase II and IV and plasmid or integron mediated beta-lactamases [7] [8] [9] . Carbapenems (meropenem, doripinem, imipenem) are the last line drugs for treatment of MDRPA but resistance to these drugs has been detected in some strains [10] . These strains produce carbapenem hydrolyzing enzymes (carbapenemases) which mediate resistance to carbepenems. Carbapenemases are mostly MBLs and include: Imipenemase (IMP), Australian imipenemase (AIM), Sao Paolo MBL (SPM), Verona integron encoded MBL (VIM), Seoul imipenemase (SIM) German imipenemase (GIM) and most recently New Delhi MBL (NDM) [11] . MBLs have a worldwide distribution and have been identified virtually in all continents and their spread is continuing [12] . This study was carried out to determine the resistance of P. aeruginosa against commonly used antibiotics and to determine MBL production.

The antimicrobial susceptibility of P. saeruginosa is given in Table 1 and Table 2.

More than half of the isolates (52.5%) were males and 44.4% were females.

More than three quarters (77.8%) of the isolates were from the intensive care unit (ICU), 15.2% were from other wards while 2% were obtained from outpatient department. The specimens taken were mainly tracheal aspirates (67.7%) while 23.2% were urine samples and 8.1% pus.

P. aeruginosa is a serious threat in health care settings. In this study, most isolates were from the ICU (77.8%) and the highest resistance was in ICU. This is because the ICU has one of the highest occurrence rates of nosocomial infections 20% - 30% [15] . Of the isolates tested 69.7% were resistant to piperacillin, 63.6% were resistant to aztreonam, 58.6% were resistant to levofloxacin, 55.6% were resistant to cefepime, 65.7% were resistant to ceftazidime, 68.7% were resistant to ticarcillin-clavulanate, 86.4% of urine isolates were resistant to ofloxacin, 72.2% were resistant to meropenem while 64.9% were resistance to imipenem. Of the isolates resistant to imipenem 87.3% were found to be MBL producers. A previous study carried out in Kenya in a private hospital showed that 53% of the isolates of P. aeruginosa were resistant to piperacillin and aztreonam, whereas 100% were resistant to ceftazidime, cefepime, tobramycin, gentamicin, amikacin and ciprofloxacin, in this study the results differ slightly [16] . Also, majority of our isolates were from the (ICU 77.8%), 15.2% were from other wards while 2% were from outpatients. Majority of our isolates were tracheal aspirates 67.7%, 23.2% were urine samples while 8.15 % were from pus, a similar study carried out Kenyain the Aga Khan University Hospital, of the isolates tested three (5%) were isolated from urine, four (7%) from blood, 17 (30%) from wounds (purulent), 30 (53%) from respiratory tract specimens, and the remaining three (5%) from various other specimens [16] .

The results obtained are comparable to a study carried out in Iran in 2015 [17] whereby the rate of resistance to imipenem was 72% while MBL production identified on isolates resistant to imipenem was 88.9% this was slightly higher compared to our study. A study carried out in a private hospital in Kenya in 2008 during an outbreak of P. aeruginosa infection to characterize the betalactamases content of carbapenem resistant P. aeruginosa found that all carbapenem resistant isolates were MBL producers and the gene isolated was VIM-2 [16] . These findings were slightly higher than the results we obtained. A study carried out in Tunisia showed that all the strains tested were resistant to all antipseudomonal drugs that is betalactams, aminoglycosides and fluoroquinolones, only 67% of the strains tested were MBL producers [18] . Variation in results obtained differ due to multiple factors which include geographical location, the drugs that are prescribed to treat P. aeruginosa infections ,the dosing regimen and local hospital practices in dealing with patients with resistant pathogens [19] [20] .

It’s important to note that resistance to carbapenems is not only due to MBL production but could also be due to many other mechanisms. These mechanisms include secondary changes in regulatory system of MBL gene expression, outer membrane permeability, active efflux systems in bacterial membrane and/or multiplication of structure gene. The most common mechanism of resistance to carbapenems besides MBL production is loss or alteration of the outer membrane porin protein OprD [11] [21] . The porin protein OprD is the major portal of entry for carbapenems [22] while impermeability due to loss of the OprD porin or upregulation of the active efflux pump system in the cytoplasmic membrane of the P. aeruginosa causes non-MBL resistance. In our study (12.7%) of the isolates were non-MBL producers [23] . This type of resistance requires the presence of AmpC (inducible or stably derepressed) [24] . From this study it is quite evident that MBL poses a serious risk in health setups considering that MBL resistant isolates can be resistant to all betalactams posing a serious problem in the treatment of P. aeruginosa infections.

P. aeruginosais highly resistant to the drugs currently used for treatment and also resistance to carbapenems is largely due to MBL production. It’s necessary to have a routine surveillance of MBL production in order to guide the physicians on the most effective treatment regimen and also to prevent further spread of the enzymes to other bacterial groups like the enterobacteriaceae family. It’s also important to test various combinations of drugs for treatment of infections that are resistant to carbapenems and use of polycationic antimicrobials (colistin and polymyxin B) should be considered for the carbapenem resistance isolates and also such antimicrobial susceptibility should regularly be tested.

I would like to thank Kenyatta national hospital for allowing me to carry out this study in their institution.

JN developed the concept and drafted the proposal and the manuscript. Miss. SO, Dr. AM and Dr. MM guided in the drafting the proposal and the manuscript and clean-up of the same.

None.

This study was approved by KNH-UoN Ethics and research committee which is a committee that regulates research and ensures adherence to ethical principles to help safeguard the dignity rights safety and well-being of all actual or potential research participants by vetting proposals and overseeing conduct of research.

JN is Masters student at the University of Nairobi School of Medicine Department of Microbiology. Miss. SO, DR. AM and DR. MM are all lecturers in the University of Nairobi, Department of Microbiology with vast experience in Microbiology and in proposal development.

Karuitha, J.N., Akinyi, O.S., Njeri, M.A. and Marianne, M. (2018) Prevalence and Antimicrobial Susceptibility Profile of Metallo-β-Lactamase Producing Pseudomonas aeruginosa Isolates at Kenyatta National Hospital. Advances in Microbiology, 8, 885-893. https://doi.org/10.4236/aim.2018.811059