10-Years Hospital Experience in Pseudomonas stutzeri and Literature Review

Pseudomonas stutzeri is infrequently isolated from clinical material and rarely associated with invasive infections in human. During the past decade we have witnessed a significant increase in the number of P. stutzeri isolations from clinical material. Review of the hospital’s experience revealed 93 isolations, the vast majority were from wounds and urine. Eighteen patients suffered from Pseudomonas stutzeri bacteremia. Ten patients died (10.8%) from whom only in two cases, death could be directly attributed to the infection. Despite the significant increase in P. stutzeri isolation from clinical material, it’s still rarely associated with adverse clinical outcome and usually represents colonization rather than infection.


INTRODUCTION
Pseudomonas stutzeri is an aerobic, nonfermenting, active, gram-negative oxidase-positive bacteria.It is mostly a saprophyte found in soil, water, and rarely leads to serious community or nosocomial acquired infections [1].Cases of P. stutzeri infection concern typically immunocompromised patients with underlying diseases or previous surgery [2].The most common reported sites of clinical isolates are surgical wounds, blood, respiratory tract, and urine [3,4].Previous literature review showed that when P. stutzeri is isolated from clinical material it most likely represents colonization in hospitalized patients and uncommonly indicates pathogenicity [2].During the past decade we have witnessed a significant increase of P. stutzeri isolations from clinical material in our medical center.The clinical significance of this increase remains unclear.The present study aimed to study the clinical significance of P. stutzeri isolations, type of antimicrobial therapy prescribed, antimicrobial susceptibility patterns, and determine the correlation between species isolation and clinical outcome.In addition, we have reviewed the literature on P. stutzeri infections.

MATERIALS AND METHODS
The microbiology computer records of Emek medical center, during 10 years period (2000-2010), were reviewed providing a list of all P. stutzeri isolations from clinical material.Infection was defined when P. stutzeri was isolated from a sterile site.The hospital medical charts for each isolate were reviewed and the following data were recorded: age, sex, site of isolation, the clinical setting, type of antimicrobial therapy (if prescribed), antibacterial Address correspondence to this author at the Department of Medicine D, Emek Medical center, Afula 18101, Israel; Tel: 972-4-6494520; Fax: 972-4-6494518; E-mail: bisharat_na@clalit.org.ilsusceptibility patterns of P. stutzeri isolates, number of blood culture sets obtained and number of sets that grow microorganisms, and outcome.Antimicrobial treatment failure was defined when the local or systemic clinical signs of infection persisted, with or without isolation of the pathogen from a sterile site, despite 3 days of antimicrobial therapy.We also retrieved an annual list of all pseudomonas spp.isolations during the study period.
Pseudomonas stutzeri isolates were identified initially by their typical wrinkled and dry colony morphology on MacConkey agar and subsequently through their metabolic profile as established till the year 2005 by the API non-Enterobacrteriaceae system (bioMérieux, France) and later on by Vitek II GN (Gram negative) card (bioMérieux, France).Antibiotic susceptibility testing was carried out using E Test (bioMérieux, France) and later on by employing the API Gram negative antimicrobial susceptibility testing (AST) card # NO98 (bioMérieux, France).The following antimicrobials were tested in the study: gentamicin, amikacin, ofloxacin, ciprofloxacin, amoxicillin-clavulanate, piperacillin, piperacillin-tazobactam, cephalothin, cefuroxime, ceftriaxone, cefotaxime, ceftazidime, cefepime, imipenem, meropenem, ertapenem, trimethoprim-sulfamethoxazole, nitrofurantoin, and polymyxin B.
The study was approved by the local ethics committee.
The number of isolations increased significantly from 2000 to 2010, the highest number of isolations was identified during 2010 (n=24).Stratifying the data according to the site of isolation (sterile or non-sterile) showed that nearly 74% of isolations from sterile sites (blood, synovial fluid, CSF, and peritoneal fluid) occurred during 2005-2010.This was in complete contrast to 3 isolations only from sterile sites during the 1990's at our medical center.
Twenty nine patients had P. stutzeri isolated from the urinary tract (Table 1), 65% suffered from chronic comorbiditeis, the mortality rate in this group was ~10%.Fifteen patients (52%) received empirical antimicrobial therapy (Table 2).Only 58% of the patients (n=17) complained of symptoms suggestive of urinary tract infection, the rest (42%) were asymptomatic and were not treated and none required therapy afterwards.Of those who were treated, nearly 66% received an empirical antimicrobial therapy that was eventually inappropriate (cefuroxime and nitrofurantoin) (Table 2).Three patients died in this group, all of whom received an empirical antimicrobial treatment active against P. stutzeri, their death was attributed to cardiovascular (n=2) and pulmonary causes (n=1).None of the patients in the whole group suffered from adverse outcomes directly related to the infection or lack of therapy.
In 26 cases P. stutzeri was isolated from superficial wounds, pressure sores, and post-operative wounds (Table 1), the mean age of the patients in this group was 33.4 (range 4-93).A third of the patients suffered from chronic comorbidities.Only in six cases a local anti-pseudomonal therapy was prescribed, none of the patients developed an invasive infection that required parenteral therapy.Three patients died (11.5%), two of whom due to massive stroke (n=1) and one due to nosocomial pneumonia (n=1).Ten patients had P. stutzeri isolated from the ear canal (Table 1), only five received empirical anti-pseudomonal therapy (3 received parenteral therapy and two received topical treatment), the other five received amoxicillin (n=3) and cefuroxime(n=2).In 10 cases P. stutzeri was isolated from other sites including synovial fluid (n=2), peritoneal fluid (n=4), cerebrospinal fluid (n=1), and conjunctiva (n=3).In 8 cases (80%) an empirical anti-pseudomonal therapy was prescribed.No death was reported in this group.
The antibiotic susceptibility patterns of isolates reviewed in the current study are shown in Table 3.During the study period there were 9971 isolations of Pseudomonas aeruginosa and Pseudomonas spp.from clinical samples with mild and steady increase over the past decade.P. stutzeri had comprised only ~ 0.9 % of all Pseudomonas isolations.

DISCUSSION
Review of the hospital records during the past decade showed that despite the gradual increase in P. stutzeri isolations, the microorganism is still infrequently isolated, representing nearly 1% of all Pseudomonas isolations, and when it is isolated it frequently represents colonization rather than infection without significant pathogenicity.Ten patients died all of whom suffered from multiple and chronic comorbidities.Excluding two cases, death could directly be attributed to other, and rather significant, comorbidities than to the presence of P. stutzeri in the clinical material.
The antibiotic susceptibility patterns of the isolations are consistent with prior studies showing that the microorganism is almost invariably susceptible to aminoglycosides, quinolones, carbapenems (excluding ertapenem) antipseudomonal penicillins, polymyxin, and trimethoprimsulfamethoxazole [2,3,5,6].Excluding ceftazidime, third and fourth generation cephalosporins are not optimal therapies for P. stutzeri infections with a coverage rate ranging from 50-70%.P. stutzeri isolates were generally more sensitive than Pseudomonas aeruginosa strains (data not shown; NB) consistent with previous observations [7].
Literature review revealed that reported cases of P. stutzeri infections are primarily sporadic with very few outbreaks that were attributed to contamination of intravenous fluids [8], water system used for hemodialysis [9], or soap used to prepare skin for intravenous insertions [10], all of which occurred during the 1970's and 1980's.To our knowledge, no other outbreaks of P. stutzeri infections had occurred since then.Communityacquired infections caused by P. stutzeri have included pneumonia with empyema [11,12] and without empyema [13,14] including one case in a previously healthy child [15].P. stutzeri has also been associated with septicemia [9,[16][17][18][19][20] and bacteremia [21], as well as endocarditis on a prosthetic mitral valve [22], and a case of endocarditis with relapse after several years [23].Meningitis due to P. stutzeri has also been described [24][25][26].Bone and joint infections included vertebral osteomyelitis in a previously healthy young man [27], infection of an open fracture of the femur [28], hip joint infection [29], and a case of prosthetic knee infection [30].Pediatric cases include calcaneal osteomyelitis in a healthy 12-year-old boy who sustained a nail puncture through his sneaker [31], and a child with knee arthritis following knife puncture wound [32].Other reports include continuous ambulatory peritoneal dialysis (CAPD)-P.stutzeri associated peritonitis [33], conjunctivitis [34] and corneal infections [35].Cases of nosocomial transmission of P. stutzeri include secondary bacteremia caused by contamination of a dialysate, in hemodialysis patients [9]; endophthalmitis after cataract surgery [36]; orbital abscess after eye surgery [37]; and brain abscess after subdural grid implantation before surgery for refractory epilepsy [38].
In summary, the isolation of P. stutzeri from clinical material rarely indicates pathogenicity.Obviously, isolation of P. stutzeri from sterile sites should be given serious consideration prior to formalizing the cause of the infection and administer appropriate antimicrobial therapy.In contrast, isolation of P. stutzeri from non-sterile sites rarely indicates pathogenicity and therapy should be guided by the clinical symptoms and signs.

Table 2 . Types of Antimicrobial Therapy Prescribed for Patients Infected (or Colonized) with Pseudomonas stutzeri
Numbers in parentheses indicates no. of patients who died.§ Empirical antimicrobial therapy.* Cases where antimicrobial therapy was eventually switched to anti-pseudomonal therapy.