Nosocomial Infections Caused by ESBL

Risk Factors for Colonization and Infection with ESBL Producers

Patients at high risk for developing colonization or infection with ESBL-producing organisms are often seriously ill patients with prolonged hospital stays and in whom invasive medical devices are present (urinary catheters, endotracheal tubes, central venous lines) for a prolonged duration. The median length of hospital stay prior to isolation of an ESBL producer has ranged from 11 to 67 days, depending on the study [4].

Heavy antibiotic use is also a risk factor for acquisition of an ESBL-producing organism. Several studies have found a relationship between third-generation cephalosporin use and acquisition of an ESBL-producing strain. Furthermore, a tight correlation has existed between ceftazidime use in individual wards within a hospital and prevalence of ceftazidime-resistant strains in those wards. In a survey of 15 different hospitals, an association existed between cephalosporin and aztreonam usage at each hospital and the isolation rate of ESBL-producing organisms at each hospital [5].

The use of a variety of other antibiotic classes has been found to be associated with subsequent infections due to ESBL-producing organisms. These include quinolones, trimethoprim-sulfamethoxazole, aminoglycosides and metronidazole. Conversely, prior use of ß-lactam/ß- lactamase inhibitor combinations, penicillins, or carbapenems seems not to be associated with frequent infections with ESBL-producing organisms [6].

Modes of Spread of ESBL-Producing Organisms within Hospitals

A common environmental source of ESBL-producing organisms has occasionally been discovered. Examples have included contamination of ultrasonography coupling gel, bronchoscopes, blood pressure cuffs and glass thermometers (used in axillary measurement of temperature). Cockroaches have been implicated as possible vectors of infection; in one study, ESBL- producing Klebsiella pneumoniae isolated from cockroaches was indistinguishable from those infecting patients. ESBL-producing organisms have been isolated from patients' soap, sink basins and babies' baths, but the contribution of this environmental contamination to infection was impossible to determine [7].

Present evidence suggests that transient carriage on the hands of health care workers is a more important means of transfer from patient to patient. Hand carriage has been documented by most but not all investigators who have sought it. In these instances, the hand isolates were genotypically identical to isolates which caused infection in patients. Hand carriage by health care workers is usually eliminated by washing with chlorhexidine or alcohol-based antiseptics. However, prolonged, persistent skin carriage in a nurse with chronic dermatitis was documented. The use of artificial nails may also promote long-term carriage and has been associated with at least one outbreak [8].

The hands of health care workers are presumably colonized by contact with the skin of patients whose skin is colonized with the organism. It is important to recognize that many patients may have asymptomatic colonization with ESBL-producing organisms without signs of overt infection. These patients represent an important reservoir of organisms. For every patient with clinically significant infection with an ESBL-producing organism, at least another patient exists in the same unit with gastrointestinal tract colonization with an ESBL- producer. In some hyperendemic intensive care units and transplants units, 30 to 70% of patients have gastrointestinal tract colonization with ESBL- producers at any one time [9].

Primary gastrointestinal carriage of ESBL-producing Klebsiella pneumoniae is an independent variable Abdelmoktader A and El Far AT. Nosocomial Infections Caused by ESBL. Vaccines Vacccin 2019, 4(1): 000128.

associated with infection with ESBL-producing Klebsiella pneumoniae. At least 80% of patients with infection with ESBL-producing Klebsiella pneumoniae can be documented to have prior gastrointestinal tract carriage. Patients who develop infection usually do so within weeks of acquiring gastrointestinal tract colonization (range= 0 to 90 days) [10].

Infection Control Interventions to Overcome ESBL-Producing Organisms

Nosocomial bacterial infections are a major focus of concern for infection control programs. Such infections may occur as an outbreak (or epidemic) or may become established as a regular occurrence (endemic). Control of endemic ESBL producers is difficult, and may only be possible after significant nursing and medical reorganization, at substantial financial cost [11].

Therefore, control of the initial outbreak of ESBL- producing organisms in a hospital or specialized unit of a hospital is of critical importance .The initial stages of the infection control program in a hospital or unit which has not previously been affected by ESBLs should therefore include (i) performance of rectal swabs to delineate patients colonized (but not infected) with ESBL producers, (ii) evaluation for the presence of a common environmental source of infection, (iii) a campaign to improve hand hygiene, and (iv) introduction of contact isolation for those patients found to be colonized or infected [12].

Contact isolation implies use of gloves and gowns when contacting the patient. Several studies have documented that this practice alone can lead to reduction in horizontal spread of ESBL-producing organisms. However, compliance with these precautions needs to be high in order to maximize the effectiveness of these precautions [12].

In Marcadé G, et al. [13] were forced to close a ward temporarily in order to adequately control an outbreak which had been unresponsive to conventional measures.

A number of groups have previously attempted selective digestive tract decontamination as a means of interrupting transmission of ESBL-producing organisms. Erythromycin-based therapies have not been effective. However, three groups successfully used selective digestive tract decontamination with polymyxin, neomycin, and nalidixic acid, colistin and tobramycin, or norfloxacin to interrupt outbreaks of infection with ESBL- producing organisms that had not been completely controlled using traditional infection control measures. It should be noted that in many hospitals at least 15 to 30% of ESBL-producing organisms are quinolone resistant and therefore unlikely to be suppressed by use of norfloxacin prophylaxis. Additionally, multidrug-resistant isolates are unlikely to respond to selective digestive decontamination using aminoglycosides [14].

An alternative approach to digestive tract decolonization has been decolonization of the nasopharynx. A study has utilized a nasal spray with povidone-iodine as a means of decolonizing the upper respiratory tract. In this study (performed in a neurologic rehabilitation unit), only 1 of 10 patients had gastrointestinal carriage with an ESBL-producing organism but all had nasotracheal colonization [15].

Although infection control procedures continue to play a central role, changes in antibiotic policy may play an even greater role in this setting. It was suggested that use of ß-lactam/ß-lactamase inhibitor combinations, rather than cephalosporins, as empirical therapy for infections suspected as being due to gram-negative bacilli, may facilitate control of ESBL producers. The mechanism by which these drugs may reduce infections with ESBL producers is not certain. It should be noted, however, that many organisms produce multiple ß-lactamases, which may reduce the effectiveness of ß-lactam/ß-lactamase inhibitor combinations [16].