The goal of this study was to characterize the microbial spectrum and antibiotic susceptibility profile of gram-negative bacteria in cancer patients. The most frequently isolated gram-negative bacteria from all clinical specimens were Klebsiella pneumonia followed by Escherichia coli (Table 1). Other studies reported that Escherichia coli and Klebsiella species were the most frequently isolated gram-negative pathogens in nosocomial infections from cancer and non-cancer patients [9, 10]. Similarly, Bilal et al reported that Klebsiella pneumonia was the most common isolate in their hospital in Saudia Arabia .
Klebsiella pneumonia was the main isolated gram-negative bacteria from sputum and throat (Table 1). This is consistent with the work of Hoheisel et al in Germany who reported that Klebsiella species were among the most frequent gram-negative isolates from RTI . Results in table 1 indicated that the main isolated gram-negative bacteria from blood were Escherichia coli and Pseudomonas species (Table 1). Other studies also reported Escherichia coli and Pseudomonas species to be among the most prevalent organisms causing bloodstream infections in USA .
In the present study, 18% of cancer patients developed SI (data not shown). This is consistent with other studies which reported significant surgical site infection rates in cancer treatment centers [14, 15]. As shown in table 1, the most commonly isolated gram-negative bacteria from SI were Klebsiella pneumonia, Escherichia coli, and Pseudomonas aeruginosa. Vilar-Compte et al reported that Escherichia coli and Pseudomonas species were the most commonly isolated bacteria from surgical site infections at a cancer center in Mexico . The main isolated organisms from urine were Escherichia coli and Klebsiella pneumonia (Table 1). This is reminiscent of the study by Espersen et al who demonstrated that UTI due to Escherichia coli were the most frequent infections in patients with myelomatosis .
In addition to the present study, the isolation of Burkholderia cepacia and other less-frequent gram-negative bacteria had been reported in other studies of nosocomial infections in cancer and non-cancer patients [17–19] (Table 2). The low prevalence of Salmonella, Shigella, and Yersinia species reported in our study was not unusual in the realm of nosocomial infections in cancer patients. In his study on patients with acute leukemia, Gorschluter et al reported low frequency of enteric infections by Salmonella, Shigella, Yersinia, and Campylobacter .
As in tables 5 and 6, all gram-negative species examined were highly resistant to third-generation cephalosporins. Reports from Korea and other parts of the world indicted that nosocomial infections caused by Enterobacter, Citrobacter, and Serratia species were also resistant to third generation cephalosporins .
Isolates producing ESβL confer resistance to all β-lactam agents and to other classes of antimicrobial agents, such as amino glycosides and flouroquinolones, thus making it difficult to treat infections they produce . Reports indicate a significant increase in ESβL-producers in recent years . Invasive procedures, specifically catheterization, prolonged hospital stay and confinement in an oncology unit were found to be associated with ESβL production . Ceftazidime and cefotaxime resistance are potential markers for the presence of Extended-Spectrum β lactamases (ESβL). Aztreonam resistance is also a potential marker for the presence of an ESβL-producing organism. Levels of resistance to aztereonam among gram-negative isolates (Tables 5 and 6) were higher than those reported few years ago in Egypt . In addition, there were high percentages of cefotaxime/ceftazidime-resistant gram-negative isolates. All of this suggested ESβL production (Tables 5, 6, 7). However, further confirmatory tests are needed to confirm the presence of ESβL enzymes in such isolates. This is an important future avenue specially that previous reports suggested that ESβL-producing strains were endemic in Egypt .
Compared with second-generation quinolones (ciprofloxacin), the newest fluoroquinolones (levofloxacin, gatifloxacin) have enhanced activity against gram-positive bacteria with only a minimal decrease in activity against gram-negative bacteria . However, the newer generation quinolones are still quite active against most Enterobacteriaceae (such as Enterobacter, Escherichia, Klebsiella) and non-fermentative gram-negative bacilli (such as Acinetobacter) with the exception of Pseudomonas aeruginosa . Results in tables 5 and 6 demonstrated that whereas Klebsiella, Pseudomonas, and Acinetobacter were relatively more susceptible to newer quinolones than ciprofloxacin, Escherichia coli was more susceptible to ciprofloxacin. Enterobacter was particularly susceptible to levofloxacin. Thus, an older or newer quinolone may be more active depending on the particular gram-negative species involved.
Previous studies in Egypt reported that resistance to imipenem was totally absent or very low [25, 28]. A similar observation was made in a study in Turkey . Other studies in Turkey, Italy, and France reported the presence of low levels of resistance to imipenem [30–33]. Acinetobacter and Pseudomonas species exhibited the highest resistance levels to imipenem. Enterobacter still exhibited considerable resistance to imipenem. Escherichia coli and Klebsiella exhibited lower, but still noticeable, resistance to imipenem. To our knowledge, this is the first study which reports significant levels of imipenem resistance in Egypt.
Escherichia coli isolates were highly resistant to ampicillin, ampicillin-sulbactam, aminoglycosides, and other antibiotics. El Kholy et al reported that Escherichia coli isolates from cancer patients in Egypt exhibited a low susceptibility pattern .
In a study conducted in Turkey, Acinetobacter baumannii was resistant to most antibiotics tested except meropenem, tobramycin, and imipenem . Results in Table 6 showed that Acinetobacter species, as well as Pseudomonas species, were highly resistant to ceftazidime, aztereonam, piperacillin, and amino glycosides as was reported in other studies [35, 36]. Some investigators noticed that geographic differences affected the resistance patterns of gram-negative bacteria such as Acinetobacter species . In such a case, local surveillance will be important in order to determine the most adequate therapy for infections caused by such organisms.
Nosocomial outbreaks of the gram-negative pathogen Enterobacter cloacae were previously reported [37, 38]. Our study confirmed previous reports which indicated that Enterobacter species isolated from hospitalized cancer patients from Egypt were highly resistant to ceftazidime, cefotaxime and aztereonam .
The phenomenon of multi drug resistant pathogens had emerged in Egypt and worldwide in recent years due to excessive antibiotic misuse [25, 39]. Thus, Pathogens resistant to cephalosporins (third or fourth generation), carbapenems, aminoglycosides, and fluoroquinolone had emerged . This study showed that gram-negative isolates can be resistant to more than one non β-lactam drug.
As indicated in table 7, the mortality rate associated with Pseudomonas infections in cancer patients was 34.1%. Previous reports also indicated high mortality rates (22%–33%) associated with Pseudomonas and Escherichia coli infections in immuno-compromised patients [40, 41]. Similarly, the mortality rate (16%) attributed to Acinetobacter species infections was not very different from mortality rates attributed to Acinetobacter species infections in other reports (14–20%) [42, 43].
The high levels of antimicrobial resistance in gram-negative bacteria can be attributed to antibiotic misuse in Egypt. Policies on the control of antibiotic usage have to be enforced and implemented to avoid the evolution of newer generations of pathogens with higher resistance, not only to the older generation drugs, but also to the relatively new ones. In addition, the entire microbial spectrum in various infection sites, and not just bloodstream pathogens, should be taken into account when initiating empirical antibiotic therapy.