Acinetobacter : An Enemy after Head and Neck Cancer Operations with Microvascular Free Flap Reconstruction?

Abstract

Background:

Patients after head and neck cancer reconstructive surgical procedures are predisposed to have post-operative surgical site infections (SSI) develop. They are very often caused by multi-drug resistant strains, including Acinetobacter baumannii as the most common one.

Methods:

The aim of the study was to determine important risk factors contributing to SSI of A. baumannii origin. The analysis included 134 head and neck cancer patients after salvage operations with microvascular free flap reconstruction. The A. baumannii was cultured in 27 of all 48 infected patients.

Results:

The following risk factors were significantly associated with A. baumannii infection: re-hospitalization before reconstructive operation (p = 0.00011), massive blood loss (p = 0.00277), and need of revision surgical procedure (p = 0.00419). Of patients with A. baumannii infection, 48% were hospitalized in a general intensive care unit (ICU) after operation that, together with prolonged intubation, constituted a strong risk factor of that infection (p = 0.01077). Mean time of hospital stay was significantly longer in the A. baumannii group (58 days vs. 35 days; p = 0.02697).

Conclusions:

Our analysis identified a subset of head and neck cancer patients after salvage operation with microvascular free flap reconstruction who are at high risk of A. baumannii infection developing. Previously hospitalized patients with extensive blood loss and need of surgical revision necessitate increased monitoring for the development of this complication. Mechanical ventilation and hospital stay in an ICU should be shortened maximally or avoided in that challenging group of patients. Early recognition of patients at high risk remains a key point to prevent or limit the spread of A. baumannii infections.

During the last decade, Acinetobacter baumannii has emerged as one of the most challenging and demanding micro-organisms. It is one of the so-called ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, A. baumannii, Pseudomonas aeruginosa, and Enterobacter spp.), indicating their “escape” from the effects of antibacterial agents or the non-existence of newer active antibiotic agents [1]. Among the risk factors for colonization or infection with that multi-drug resistant (MDR) pathogen are prolonged hospitalization, intensive care unit (ICU) admission, recent surgical procedures, antimicrobial agent exposure, central venous catheter use, prior hospitalization, nursing home residence, and local colonization pressure on susceptible patients [2].

Patients undergoing head and neck oncologic surgical procedures are at a special risk for development of such a complication [3 –5]. Because it has been proven that SSI is associated with increased morbidity and death [6,7], prophylactic activities should be applied to minimize the rate of it.

The aim of the study was to determine the important risk factors contributing to A. baumannii infection in patients with head and neck cancer after salvage surgical procedures with microvascular free flap reconstruction to propose an appropriate prevention. The detailed aims concerned the analysis of the potential sources and ways of infection spread, sensitivity of the pathogen to various antibiotic agents, response to treatment time, as well as the impact of the infection on the long-term outcome. The problem of colonization by aggressive A. baumannii hospital strains and the question of the validity of that pathogen eradication in such a group of patients were also undertaken in the Discussion section.

Methods

The analysis included 134 consecutive head and neck cancer patients after salvage operation with microvascular free flap reconstruction. All procedures were performed in the Department of Otolaryngology, Head and Neck Surgery of Poznań University of Medical Sciences (a 70-bed tertiary referral center) in 2014–2018. Mean age in the group was 54 years (range: 38–69 years); 107 patients were male and 27 were female. Detailed patient characteristics can be found in Table 1.

Table 1.

Patient Characteristics, Statistical Analysis of Risk Factors Contributing to Acinetobacter baumannii Infection

Risk factor	Number of patients			p (Acinetobacter baumannii infection vs. all)	p (Acinetobacter baumannii infection vs. with SSI)
Risk factor	All	With SSI	With Acinetobacter baumannii infection	p (Acinetobacter baumannii infection vs. all)	p (Acinetobacter baumannii infection vs. with SSI)
Gender (female:male)	134 (27:107)	48 (8:40)	27 (3:24)	^*0.45274	^*0.24157
Average age (y)	54	56	55	^**0.87246	^**0.78361
Smoking	108 (81%)	42 (88%)	23 (85%)	^*0.13114	^*0.58242
Alcohol overuse	64 (48%)	31 (65%)	18 (67%)	^*0.00359	^*0.73220
Diabetes	17 (13%)	12 (25%)	9 (33%)	^*0.00138	^*0.13057
Malnutrition (BMI <17)	53 (40%)	31 (65%)	17 (68%)	^*0.00001	^*0.79012
Re-hospitalization	43 (32%)	22 (46%)	19 (70%)	^*0.01089	^*0.00011
Re-operation	87 (65%)	32 (67%)	21 (78%)	^*0.75233	^*0.06408
Previous radio-/ radio-chemotherapy	87 (65%)	33 (69%)	19 (70%)	^*0.48823	^*0.78360
Average length of operation (h)	7,5	8	8,5	^**0.48153	^**0.38592
Time of hospital stay before operation (d)	3	4	5	^**0.79561	^**0.23847
Time of hospital stay (d)	35	41	58	^**0.04792	^**0.02697
Stay at ICU	27 (20%)	15 (31%)	13 (48%)	^*0.01670	^*0.01077
Mechanical ventilation >3 d	27 (20%)	15 (31%)	13 (48%)	^*0.01670	^*0.01077
Massive blood loss (>500 mL)	37 (28%)	22 (46%)	18 (67%)	^*0.00042	^*0.00277
Revision surgical procedure	21 (16%)	19 (40%)	16 (59%)	^*0.00000	^*0.00419
Titanium plate	19 (14%)	12 (25%)	8 (30%)	^*0.00730	^*0.40095
Tracheotomy	93 (69%)	33 (69%)	19 (70%)	^*0.90247	^*0.78360

SSI = surgical site infection, BMI = body mass index, ICU = intensive care unit.

Chi-square test, ^**Student t test.

The following variables were recorded as risk factors contributing to A. baumannii infection for all patients: Pre-operative variables such as age, gender, body mass index, history of smoking and alcohol consumption, relevant co-morbidities (such as diabetes mellitus), previous radiotherapy, chemoradiotherapy, operation or hospitalizations (in the same or another department within the year before the operation), time of hospital stay before the operation; operative variables, including duration of operation, amount of blood loss, tracheostomy, implants and post-operative variables such as hospital stay in the ICU, prolonged mechanical ventilation, need of revision surgical procedure, length of hospitalization.

Statistical analysis was conducted to determine whether these factors constitute risks for A. baumannii infection. The chi-square test was used for categoric data, while the Student t test was used for continuous variables. The level of significance was set at p < 0.05.

The article was prepared in accordance with the ethical standards of The Institutional Review Board of the Poznań University of Medical Sciences and with the Helsinki Declaration (1964, amended most recently in 2008) of the World Medical Association.

Results

In the analyzed group, there were 398 swabs performed for microbiologic testing altogether (266 post-operatively). The overall post-operative infection rate was 36% (31% surgical site infection [SSI]). In 42 swabs (in 27 of all 48 infected patients), A. baumannii was cultured. All cases were qualified as SSI (patients manifested clinical and biochemical signs of infection).

In the A. baumannii group, there were 24 men and three women with a median age of 55 years (range: 38–64 years). The most common primary tumor site was the tongue and the floor of the mouth (16 patients total), followed by the oropharynx (eight patients), hypopharynx (two patients), and maxillary sinus (one patient). Squamous cell carcinoma dominated in histopathologic diagnoses (26/27 patients). In 18 patients, free radial forearm flaps were used for reconstruction; in six, anterior thigh flaps were used, while in three, both types of flaps were used (as a consequence of flap necrosis). Titanium reconstruction plates were used in eight patients. The other analyzed data are presented in Table 1.

Results of the statistical analysis are presented in Table 1. Epidemiologic data such as age and gender did not differ significantly in groups with and without SSI as well as compared with the A. baumannii infection group. A comparable percentage of patients were smokers and drinkers in the analyzed subgroups; patients who abused alcohol were at significantly higher risk of SSI (p = 0.00359); however, A. baumannii was not considerably more common among them (p = 0.73220).

The following risk factors were significantly associated with A. baumannii infection: Re-hospitalization before reconstructive operation (p = 0.00011), massive blood loss (p = 0.00277), and need of a revision surgical procedure (p = 0.00419). Of patients with A. baumannii infection, 48% were hospitalized in a general ICU after operation, which, together with prolonged intubation, constituted a strong risk factor for that infection (p = 0.01077). Mean time of hospital stay was significantly longer in the A. baumannii group (58 days vs. 35 days; p = 0.02697).

The antibiotic susceptibility/resistance profile of all A. baumannii isolates was determined using 10 antibiotic agents (Table 2). The highest resistance was noted for ciprofloxacin (43%) and ampicillin/sulbactam (38%). Seventy-seven percent of isolates were susceptible to carbapenems, while 100% were susceptible to tigecycline and colistin. Species resistant to carbapenems were cultured from patients treated with these antibiotic agents previously.

Table 2.

Susceptibility/Resistance Pattern of All 42 Acinetobacter baumannii Isolates to Various Antibiotic Agents

Antibiotic	Sensitive		Resistant
Antibiotic	n	%	n	%
Ampicillin/sulbactam	26	62	16	38
Cefepime	28	67	14	33
Ceftazidime	29	69	13	31
Imipenem	31	74	11	26
Meropenem	34	81	8	19
Amikacin	32	76	10	24
Tigecycline	42	100	0	0
Ciprofloxacin	24	57	18	43
Piperacillin/tazobactam	36	86	6	14
Colistin	42	100	0	0

In most patients (21/27), meropenem (usually 3 × 1 g IV, in severe infections 3 × 2 g IV) was used. In more resistant cases (5/27), piperacillin/tazobactam (3 × 4.5 g IV) or colistin (1/27 patients; 3 × 2 mL n j IV) were administered. The treatment was continued for 16–22 days until bacteriologic/clinical clearance. Control swabs were performed every seven days. Increased resistance to antibiotic agents was noticed in most of the control isolates.

Discussion

Patients after major head and neck surgical procedures are predisposed to have post-operative complications develop. A SSI seems to be the most frequent one—in the literature data, SSIs count for 3% to even 41% [8]. Microvascular free flap reconstruction techniques, connected with prolonged duration of operation and length of hospital stay as well as greater degree of surgical invasion, create an additional strongly documented risk [3,4,9,10].

In the group analyzed by the authors, the operative field was clean-contaminated in all cases—it induced us to administer standard antibiotic prophylaxis, covering specific microflora of the oral cavity and pharynx (1.5 g of ampicillin/sulbactam introduced before the operation and continued every six hours for the next 24 hours). Despite this step, the level of SSI exceeded the level of 30%. In 56% of swabs, A. baumannii was cultured.

Statistical analysis revealed that some factors were notably related to A. baumannii SSI. Prolonged (>3 days) endotracheal intubation with mechanical ventilation to support vital functions after the operation constituted an important risk factor for A. baumannii infection to develop (p = 0.01077). The same findings are presented by many authors [11,12]. The ability of A. baumannii to survive for extended periods on humid surfaces, including a life-supporting device, is notorious and is likely important for transmission within the healthcare setting. Confirmed capacity of biofilm formation by clinical isolates of MDR A. baumannii reduces the antimicrobial effects of commonly used antiseptic agents, leading to long-term persistence in the hospital environment [13].

Most patients after reconstructive head and neck surgery require ventilation support for at least 24 hours post-operatively. Because of the length and specificity of the operations, gradual and smooth awakening is of great importance. While the course of emergence cannot be changed, the only way to avoid infection is identification of the potential source and respect for the rules of basic hygiene and aseptic procedures. The need to extubate the patients as soon as possible should also be emphasized.

Another important factor increasing the risk of A. baumannii infection was previous stay in the hospital (the same or another department within the year before the operation) (p = 0.00011). Our study also showed a correlation between A. baumannii infection and stay in the ICU (p = 0.01077). Both results can be explained by the fact that in such patients, their normal microflora is replaced partly with the pathogens from the hospital environment, which especially in the ICU could be multi-resistant. Such colonization can promote infection development at the time of the weakened immunity response.

Baran et al [14] reported that there is a three-fold higher risk of imipenem-resistant A. baumannii infection in an ICU (p = 0.005). If possible, considering general patient condition, it would be a good trend not to hospitalize patients after operation with microvascular free flap reconstruction at the main hospital ICU but rather in the small ward with increased monitoring within the native department.

Another crucial correlation was found between A. baumannii SSI and increased intra-operative blood loss (p = 0.00277). It might suggest that improvement of techniques and surgical skills to reduce blood loss is of great importance. Moreover, allogenic blood transfusion was thought to cause an immunosuppressive effect that increased the likelihood of infection [15]. Weaker defense against infections is also typical for patients with such co-morbidities as diabetes mellitus or malnourishment [16,17]. Both factors were also of significant importance in SSI in our study group (p = 0.00138, p = 0.00001); however, they did not correlate specifically with A. baumannii infection.

The ability of A. baumannii strains to adhere to surfaces and to form biofilm is an important mechanism that explains its higher pathogenicity in cases with the implantation of any prostheses or wafers. Rodríguez-Baño et al [18] and Tripathi et al [19] reported 63% biofilm formation in A. baumannii isolates. In our material, surgical sites of patients with mandible reconstruction were significantly more often infected (p = 0.00730), but not with A. baumannii isolates.

A. baumannii has a great documented ability to develop resistance to even the most potent antimicrobial agents [5]. Antimicrobial resistance among Acinetobacter spp. has increased substantially in the past decade and has created a major public health dilemma [19]. In the UK, the resistance to carbapenems, which are the mainstay in the therapy of serious infections caused by these pathogens, has increased from 0.5% in 1990 to 24% in 2011 [5]. In many hospitals, A. baumannii species have been reported to be resistant to all conventionally administered antibiotic agents [20,21].

Fortunately, in our study group, most A. baumannii species were susceptible to carbapenems; in more resistant cases, piperacillin/tazobactam and colistin were used. Species resistant to carbapenems were cultured from patients treated by these antibiotic agents in the past. Previous administration of carbapenems is a documented risk of MDR A. baumannii infection [12].

An SSI very often causes necrosis of the reconstructive flap, brings the need of another procedure, and increases the length of hospital stay [4,9,22]. In our group, there was a necessity of revision operation in 16 patients. Two of them were infected with MDR A. baumannii species. Mean time of hospital stay was significantly longer in the A. baumannii group than in all patients after reconstructive procedures (58 days vs. 35 days; p = 0.02697); it applied to all patients requiring revision surgical procedures and prolonged antibiotic use. Our results are comparable to those from the literature [23].

A. baumannii appears to be as much a colonizer as it is a true pathogen. In the Cisniros et al study [24], 51% patients were colonized with imipenem-resistant A. baumannii strains while 49% of them were infected. The mortality rate of patients with infection was higher than that of patients with A. baumannii colonization (27% vs. 11%). The authors emphasize a need to distinguish between colonization and infection to avoid unnecessary use of antimicrobial agents.

Similar conclusions are presented by Weingarten et al [23]. The authors underline that unnecessary treatment of A. baumannii colonization can lead to a significant increase of other pathogens' resistance to these antibiotic agents and can generate complications and considerable costs. Colonized patients should be isolated and monitored (clinically, biochemically, and bacteriologically). The decision to treat on the basis of a clinical culture result remains, of course, in the hands of the clinician.

Conclusions

Our analysis identified a sub-set of head and neck cancer patients after salvage surgical procedures with microvascular free flap reconstruction who are at high risk of A. baumannii infection developing. Previously hospitalized patients with extensive blood loss and need of surgical revision require increased monitoring for the development of this complication. Mechanical ventilation and hospital stay in an ICU should be shortened maximally or avoided in that challenging group of patients. Early recognition of patients at high risk, environmental hygiene measures (hand disinfection, isolation procedures, efficient equipment sterilization) remain key points to prevent or limit the spread of A. baumannii infection.

Footnotes

Funding Information

No funding was received.

Author Disclosure Statement

No competing financial interests exist.

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