- Email: [email protected]
Deep Neck Space Infections: Changing Trends in Pediatric Versus Adult Patients
Journal Pre-proof Deep Neck Space Infections: Changing trends in Paediatrics versus Adults Shivesh Maharaj, Sheetal Mungul, Sumaya Ahmed PII:
S0278-2391(19)31355-2
DOI:
https://doi.org/10.1016/j.joms.2019.11.028
Reference:
YJOMS 58992
To appear in:
Journal of Oral and Maxillofacial Surgery
Received Date: 24 September 2019 Revised Date:
24 November 2019
Accepted Date: 25 November 2019
Please cite this article as: Maharaj S, Mungul S, Ahmed S, Deep Neck Space Infections: Changing trends in Paediatrics versus Adults, Journal of Oral and Maxillofacial Surgery (2020), doi: https:// doi.org/10.1016/j.joms.2019.11.028. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier Inc on behalf of the American Association of Oral and Maxillofacial Surgeons
TITLE PAGE Deep Neck Space Infections: Changing trends in Paediatrics versus Adults Author names and affiliations: Shivesh Maharaj1 Sheetal Mungul 2, Sumaya Ahmed, 3
1)Shivesh Maharaj MBBCH, FCORL, MMED Head of Department Charlotte Maxeke Johannesburg Academic Hospital, School of Neurosciences, Department of Otolaryngology, University of the Witwatersrand, Johannesburg, South Africa. Email: [email protected] 2) Sheetal Mungul MBBCH, BSC( Biomedical science) Registrar Charlotte Maxeke Johannesburg Academic Hospital, School of Neurosciences, Department of Otolaryngology, University of the Witwatersrand, Johannesburg, South Africa. Email: [email protected] 3) Sumaya Ahmed MBBCH, FCORL, MMED Otorhinolaryngologist Department of Otolaryngology, University of the Witwatersrand, Johannesburg, South Africa. Email: [email protected]
Corresponding author: Dr S Maharaj, Academic Head of Department, email: [email protected] Present / Permanent address: Charlotte Maxeke Johannesburg Academic Hospital, School of Neurosciences, Department of Otolaryngology, University of the Witwatersrand, Johannesburg, South Africa Keywords: Deep neck space infection, Microbiology, Antibiotics
TITLE PAGE Deep Neck Space Infections: Changing Trends in Paediatrics versus Adults Author names and affiliations: Shivesh Maharaj1 Sheetal Mungul 2, Sumaya Ahmed, 3 1)Shivesh Maharaj MBBCH, FCORL, MMED Head of Department Charlotte Maxeke Johannesburg Academic Hospital, School of Neurosciences, Department of Otolaryngology, University of the Witwatersrand, Johannesburg, South Africa. Email: [email protected] 2) Sheetal Mungul MBBCH, BSC( Biomedical science) Registrar Charlotte Maxeke Johannesburg Academic Hospital, School of Neurosciences, Department of Otolaryngology, University of the Witwatersrand, Johannesburg, South Africa. Email: [email protected] 3) Sumaya Ahmed MBBCH, FCORL, MMED Otorhinolaryngologist Department of Otolaryngology, University of the Witwatersrand, Johannesburg, South Africa. Email: [email protected]
Corresponding author: Dr S Maharaj, Academic Head of Department, email: [email protected] Present / Permanent address: Charlotte Maxeke Johannesburg Academic Hospital, School of Neurosciences, Department of Otolaryngology, University of the Witwatersrand, Johannesburg, South Africa Keywords: Deep neck space infection, Microbiology, Antibiotics
ABSTRACT
Purpose: To study the clinical presentation and microbiology in patients with deep neck space infection in a developing nation so as to aid in determining relevent, appropriate and effective empiric antimicrobial treatment. To describe the demographics of pediatric verse adult patients affected and the predominant age-related subtypes of deep neck space infections
Methods: A retrospective review of patients with deep neck space infections over a 5,5-year period was conducted at the academic teaching hospitals in Johannesburg, South Africa. Diagnosis of deep neck space infection was determined by clinical, radiographic and laboratory findings. All patients received abscess drainage via either needle aspiration or surgical drainage using a sterile technique. Aerobic and anaerobic bacterial cultures and cultures for Mycobacterium tuberculosis were performed. Results were recorded, and statistical analysis was performed.
Results: A total of 107 children and 52 adults with deep neck space infections were included in the study, with 121 and 70 pus specimens retrieved. The male: female ratio was 1.14:1 for the paediatric group with a total of 53% (n=57) males and 47% (n=50) females. The adult group comprised 63% (n=33) males and 37% (n=19) females. The ratio of males: females was 1.74:1.
In the paediatric group, the mean age was 5.8 years (range 2months – 15years). Age distribution was subcategorized into <2years, 2-10years and >10years 51 patients were < 2 years of age, 50 patients were between 2-10years of age and 6 patients were older than 10years. The age distribution of adult patients ranged from 19 to 77 years, with a mean of 40.9 (+ -15.5) yrs.
2
Multi-space involvement of deep neck infection occurred in 7.5% (n=8) of paediatric cases and 59.6% (n=31) of cases in the adult population.The submandibular space was the most common affected site (73.9%) in both groups.
Conclusion: Deep neck space infections differ in clinical presentation and microbiology in adults and paediatrics. The paediatric group predominantly cultured Staph. Aureus, whereas the adult population was mainly polymicrobial. There was a poorer patient outcome in the adult population with a greater number of Intensive Care Unit (ICU) admissions , theatre visits and prolonged hospital stay.
1. INTRODUCTION Deep neck space infection is defined as infection in the potential spaces and fascial planes of the neck 1.
3
The anatomical differences in peadiatric and adult neck anatomy lead to different manifestations of the disease process. Pediatric deep neck space infections are a distinct entity from adult deep neck space infections as lymph nodes are more predominant in different anatomical sites in children, resulting in different clinical presentations and inciting pathogens from drainage areas affected 2. The mainstay of treatment currently involves antibiotics and surgical drainage when required. Antimicrobial resistance is currently a critical issue worldwide and a higher pattern of resistance is seen in lower socioeconomic countries, such as those in Sub-saharan Africa 3,4. A comparison of the microbiology of pathogens in pediatric verse adult deep neck space infections has to our knowledge, never been investigated in South Africa before. The purpose of this study is to investigate the spectrum of pathogens and patterns of antibiotic resistance in adult versus paediatric patients with deep neck space infections seen at our tertiary teaching centers. It is hypothesized that although pediatric patients are younger and more at risk of serious complications, that our adult patients with deep neck space infections are in fact more severely affected. It is also expected that an overall higher incidence of antimicrobial resistance is seen in patients from a lower socioeconomic setting and that these pathogens differ between the paediatric and adult population. Our aim is therefore to investigate the differences between paediatric and adult deep neck space infections to gain a better understanding of pathogenesis of disease and guide patient management in a resource constrained setting.
2. METHODS 2.1 A retrospective review of all patients with deep neck space infections, who were admitted to the teaching hospitals affiliated to the University of the Witwatersrand Gauteng, South Africa from the 1 July 2008 to the 30June 2017
4
was performed. These spaces include the submandibular, parotid, masticator, peritonsillar, parapharyngeal, retropharyngeal, pretracheal and prevertebral spaces. Patients with superficial skin infection, non-suppurative lymphadenitis and congenital abnormalities were excluded. Patients with non-suppurative lymphadenitis were excluded due to the absence of pus for adequate laboratory testing in our setting, The diagnosis of deep neck space infection was determined by clinical, radiographic and laboratory findings. Most patients were investigated by means of ultrasonography due to cost-effectiveness and, where necessary, a CT scan or MRI was performed. All patients received abscess drainage via either needle aspiration or surgical drainage using a sterile technique. Aerobic and anaerobic bacterial cultures and cultures for Mycobacterium tuberculosis were performed under aseptic field and technique at the National Health Laboratory Service. Patients were treated with empiric intravenous broad-spectrum antimicrobial therapy, which was then culture-directed once microbiology results were available. The results of these pus specimens from the National Health Laboratory Service was evaluated and the following characteristics reviewed: •
The presence or absence of an organism
•
What organism was identified
•
The culture results
•
The antimicrobial sensitivities
•
Additional data such as age, gender, white cell count, differential count, hemoglobin level, platelets, C-reactive protein, albumin level, HIV status and duration of hospitalization were also retrieved when available.
5
2.2 Statistical analysis with the Chi-square test was conducted using the Stata statistical program (Stata/IC 14.2 for Windows), to assess differences between patients of different age groups and with different anatomical subtypes of deep neck space infections. A p value of < 0.05 was considered statistically significant. Descriptive statistics such as percentages and frequencies were also used.
3. ETHICS Ethics approval was obtained by the Human Research Ethics Committee, University of the Witwatersrand. All personal and identifying information was kept confidential.
4. RESULTS A total of with 107 children and 52 adults with deep neck space infection were included in the study, respectively with 121 and 70 pus specimens retrieved. The male: female ratio was 1.14:1 for the paediatric group with a total of 53% (n=57) males and 47% (n=50) females. The adult group comprised of 63% (n=33) males and 37% (n=19) females. The ratio of males: females was 1.74:1.
In the paediatric group, the mean age was 5.8 years (range 2months – 15years). Age distribution was subcategorized into <2years, 2-10years and >10years 51 patients were < 2 years of age, 50 patients were between 2-10years of age and 6 patients were older than 10years. The age distribution of adult patients ranged from 19 to 77 years with a mean age of 40.9 (+ -15.5) yrs.
Multi-space involvement of deep neck infection occurred in 7.5% (n=8) of cases of paediatric patients and 65% (n=34) of adult patients. The distribution of neck space involvement in the 159 patients is illustrated in table 1. The submandibular space was the most common
6
affected site (73.9% of paediatric patients and 92.3% of adults). The average duration of hospitalization in our study was 5 days for paediatrics and 9 days in adults. The majority of adult patients required admission into the Intensive Care Unit (ICU) at some stage of their treatment and 10 of these adult patients (19%) demised. This subgroup of patients comprised 8 patients who died of overwhelming sepsis and 2 patients who died as a result of comorbid conditions namely dilated cardiomyopathy and renal failure respectively. These patients admitted to ICU had, on average, a longer duration of hospitalization of 19 days verse 7 days for adult patients not requiring ICU care. There was no significant difference in duration of hospitalization in children less than 2 years and children older than 2 years of age (p value 0.13). There was also no age-related difference regarding single space vs multispace infection, with children under 2years and older than 2 years being similarly affected (p value 0.15). There was also no significant difference in duration of hospital stay in patients with single space infection compared to those patients with multi-space deep neck infection (p value 0,103) in the paediatric population. However, the adult population presented with a much higher incidence of multispace involvement and this significantly increased duration of hospitalization as opposed to patients who had single space infection (p value > 0,05). Whereas the sources of paediatric infections were mainly as a result of upper respiratory tract infection, resulting in involvement of a variety of neck spaces, bacterial parotitis, submandibular, submental and parapharyngeal abscesses; there were 2 patients with TB parotitis. One child had TB with multispace involvement and as mirrored in the adult population, buccal, masticator and submandibular space infections occurred in older patients as a result of dental infections. All 159 patients had drainage of the abscess by either needle aspiration or surgical incision and drainage. Only 16 % of paediatric patients (17 patients) were tested for associated HIV infection as a predisposing factor due to the documentation of their status on the road to health card. Testing for HIV infection was therefore only done on the basis of clinical suspicion where the status of the child was uncertain. The prevalence of HIV infection in the adult population was, however, much higher 67% (n=36).
7
Laboratory results analysis of the paediatric population showed an average white blood cell count of 21 (x 109L), C-reactive protein of 78 mg/L, hemoglobin level of 11.2 g/dL, platelet count of 504. 57 (x 109L), patients had blood tests for anemia and 46% of these patients were anemic as seen in Table 2. Analysis of the adult population demonstrated an average white blood cell count of 17 (x 109L),, C-reactive protein of 98 mg/L and hemoglobin level of 11 g/dL, with 52% of adult patients being anaemic. 5 In paediatric patients, 97 pus samples were sent for TB microscopy, culture and sensitivity. Only 3 results were positive for TB, and all organisms were sensitive to isoniazid, with one patient having concomitant HIV infection. All of the 52 adult patients had specimens tested for TB and 2 patients were positive. Analysis of the 191 pus specimens demonstrated an identifiable organism in 71% (n=135) of all cases, with no bacterial growth in 29% (n=56) of specimens. (75.5 % identified in paediatric group and 66.5 % in the adult group). Staphylococcus aureus was the most predominant organism cultured in the paediatric group, with a prevalence of 65% of positive pus cultures. 100% of these organisms were sensitive to cloxacillin, and all were resistant to penicillin / ampicillin. This was followed by Streptococcus pyogenes with a prevalence of 5.8%. Streptococcus anginosus, Streptococcus constellatus and coagulase-negative Staphylococcus had an equal prevalence of 3.5% of positive cultures. The incidence of MRSA was 1.2% in our study and only occurred in one paediatric patient. With respect to positive cultures, there was an overall organism sensitivity to cloxacillin of 67% and overall resistance to penicillin / ampicillin of 76% The adult culture results were more diverse, with the majority of organisms being aerobic in nature (n=24), with a smaller incidence of anaerobes (n=2) and TB (n=2), respectively. Extended spectrum beta lactamase producing Klebsiella (ESBL KLESP), Enterobacter cloacae (ENTCL), Serratia marcescens (SERMA), Citrobacter freundii (CITFR) and Morganella morganii (MOGMO), interestingly all gram negative bacilli (GNB), were the 5 of 26 identified microbes (19%) in this study with reported resistance to amoxicillin – clavulanic acid, 7 of 57 microbes (12%) when all pathogens were considered. Recommended alternative antimicrobial
8
coverage for these organisms included: Ertapenem effective against MOGMO, CITFR, ENTCL, SERMA and ESBL KLESP; cefepime effective.(table 3)
5. DISCUSSION Deep neck space infection is defined as infection in the potential spaces and fascial planes of the neck, within the confines of the deep layer of cervical fascia1. These infections include lymphadenitis, cellulitis, necrotic nodes and abscesses6. Ear, nose or throat infections may spread to these spaces via contiguous or lymphatic spread and may lead to abscess formation and subsequent life-threatening complications if left untreated2.
These
complications include airway compromise, jugular vein thrombosis, carotid artery aneurysm or rupture, mediastinitis and sepsis 6. It is hypothesized that although pediatric patients are younger and more at risk of these complications, that our adult patients with deep neck space infections are in fact more severely affected. It is also expected that an overall higher incidence of antimicrobial resistance is seen in patients from a lower socioeconomic setting and that these pathogens differ between the paediatric and adult population.
The anatomical spaces deep to the deep layer of cervical fascia of the neck may be divided into those above the hyoid bone, those below it and those that involve the entire length of the neck7. Those above the hyoid bone include the peritonsillar, submandibular, parapharyngeal, masticator, buccal and parotid spaces7. Deep neck spaces below the hyoid bone refer to the anterior visceral / pre-tracheal space and spaces which involve the whole length of the neck include the retropharyngeal, danger, pre-vertebral and carotid spaces respectively 7.
9
In our study, there was no age-related difference in the spectrum of deep neck spaces affected in both groups as the submandibular space was the most commonly affected across all ages. It is also evident that although retropharyngeal abscesses are commonly seen in some countries in the younger pediatric population, it is relatively rare in our population as none of the patients presented with retropharyngeal abscesses during our study period.8,9 The incidence of peritonsillar abscess was low in our study due to our inclusion criteria, as only patients with specimens sent for microbiology were evaluated; but it was noted that adults were more affected which is consistent with the literature 2. Contrary to what is seen in other countries where children have delayed presentations due to inability to communicate and are more at risk of serious complications, the converse appears to be true to our population. Adult patients presented with more severe, often lifethreatening infections with multispace involvement, generally dental in aetiology and in some cases as a complication of tonsillitis. This demonstrates that in a lower income environment, caregivers are more vigilant about illness in children, but themselves only present to hospitals in times of absolute need, possibly due to the financial impact that this may have on themselves and their families. Adult patients had nearly double the average duration of hospitalization of their paediatric counterparts. Microbiological studies of patients with deep neck space infections demonstrated that the main inciting organisms are bacterial in origin, but these bacteria may differ in pediatrics to those seen in the adult population 7. This may be because adult deep neck space infections are generally due to dental pathology whereas pediatric deep neck space infections may be due to tonsillitis, pharyngitis, hematogenous spread and suppurative cervical lymphadenitis7. This is evidenced by the spectrum of organism seen in our study as those in paediatric patients were mainly due to Staphylococci whereas the adult culture results reflected flora of the oral cavity. Antimicrobial resistance is currently a worldwide concern and a higher pattern of resistance is seen in lower socioeconomic countries such as those in Sub-Saharan Africa 4. It is defined by Magiorakos et al., 2012 as “the ability of a specific bacterium to survive in the presence of
10
an antibiotic that was originally effective to treat infections caused by the bacterium, or acquisition of a specific antibiotic resistance mechanism”10,11,12,13,14. Bacteria may be either intrinsically resistant or may acquire resistant genes from other bacteria that are already resistant 10. Resistance is on the rise for example aerobic bacteria such as Staphylococcus aureus and this places a greater burden on our healthcare system with prolonged hospital admissions, more rapid disease progression, greater morbidity and eventual costs4. Lower-middle income countries have higher resistance patterns and are especially at risk as there are limited resources in terms of the generations of antibiotics readily available, as well as diagnostic challenges which may lead to inappropriate antibiotic use 4. This problem in lower socioeconomic countries is compounded by the limited amount of studies of a reasonable size reporting antimicrobial sensitivity outside of the intensive care setting. HIV infection was present in a much higher proportion of adults as opposed to Paediatric patients as is expected as the paediatric population are usually infected via maternal transmission, whereas adults contract the disease through sexual practice. In the overall 33% patients tested positive for HIV; however, only five of these patients had concomitant TB despite the high level of suspicion in our setting. This demonstrates that despite the national incidence of TB of 60% in patients who are HIV positive, there is a relatively lower incidence of TB in deep neck space infection in our population
15
. This may be due to a high
percentage (79%) of household contacts of confirmed TB cases on preventative treatment 15. Nutritional deficiency and compromised immune status affect a wide spectrum of patients, thus affecting various age groups, as reflected in our study. There was a high but similar prevalence of anaemia, which reflects the burden of nutritional deficiency in a lower income country. This affects immune function and hampers the body’s ability to fight infection, which may result in serious complications from conditions such as infections of the aerodigestive tract in patients who might have otherwise recovered given a competent immune system and nutritional status. This problem is compounded by poor access to healthcare in a resource constrained environment where investigations and adequate antimicrobial therapy
11
may not be readily available. It is imperative to therefore address these public health issues on a national level in order to dampen the burden on our healthcare system. In addition, access to healthcare and education are key issues which may decrease the incidence of deep neck space infections in patients of lower socioeconomic status. The World Health Organization has issued an international drug price indicator guide which provides objective information about the cost of medication16. The estimated cost of cloxacillin is 0.16 US dollars per day and the estimated cost of amoxicillin-clavulanic acid is 0.18-1.14 US dollars per day 16. Both drugs are beta-lactam antibiotics and the use of cloxacillin in the paediatric population may have not only a beneficial therapeutic effect in our setting but may also have a positive economic impact on healthcare facilities which have limited resources. However, timeout drainage of abscesses in the adult population and the administration of metronidazole may aid in the empiric medical treatment of these patients until culture directed therapy may be initiated. Development of protocols at primary healthcare facilities may also aid in the treatment of patients and limit the rate of complications and duration of hospitalization. Conclusion: Deep neck space infections differ in clinical presentation and microbiology in adults and paediatrics. The paediatric group predominantly cultured Staph aureus whereas the adult population was mainly polymicrobial. There was a poorer patient outcome in the adult population with a greater number of Intensive Care Unit (ICU) admissions , theatre visits and prolonged hospital stay. Futher research may be done in terms of appropriate investigations, surgical verse medical management options and prevention of the deep neck space infection.
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Table 1: Distribution of neck spaces affected by DNSI Deep neck space
No. of cases
Number patients
of Number patients
Age < 2years
Suprahyoid neck space
13
Age years
of Number patients 2-16 Adults
of
Buccal space
5
1
4
0
Masseteric space
1
1
-
0
Masticator space
1
-
1
0
Parotid space
9
6
3
3
Parapharyngeal space
1
1
0
4
Peritonsillar space
1
-
1
10
Submandibular space
85
48
37
31
Submental space
11
8
3
2
Temporal space
1
1
-
0
1
-
1
2
Infrahyoid neck space Posterior cervical space
14
Table 2 Study period 1/07/2008 till 30 June 2017
The Wits university teaching hospitals CMJAH and CHB.
Adults> 16 years
Peadiatrics < 16 years
Number of patients:
52
107
Number of specimens
70 specimens and
121 specimens
Gender:
33 males/ 19 females
Micro-organisms
57 males/ 50 females
26 different organisms
Mainly Staph Aureus(70%)
24 aerobic 2 anaerobic
Resistance patterns:
7 resistant to Augmentin
Resistant to penicillin Sensitive to cloxacillin
Average Lab results:
15
Average:
Wcc
17 (x 109 L)
Wcc
21 (x 109 L)
CRP
98 mg/L
CRP
78 mg/L
Hb
11 g/dl
Hb
11.2 g/dl
52 sent for TB
97 sent for TB
2 postive for TB
3 positive for TB
Table 3 : Aerobic and Anaerobic Bacteria Resistance and sensivity
Aerobic
1
Anaerobi Antibiotic
Antibiotic
c
resistance
sensitivity
Acinetobacte -
Ciprofloxacin; _amoxicillin
r baumannii
ceftazidime
- clavulanic acid
2
Morganella -
cefepime;
_amoxicillin
morganii
ertapenem
- clavulanic acid
3
16
Enterobacter -
ciprofloxacin; _amoxicillin
cloacae
cefepime;
- clavulanic
ertapenem
acid
Aerobic
4
Serratia
Anaerobi Antibiotic
Antibiotic
c
resistance
sensitivity
-
_amoxicillin
marcescens
- clavulanic acid
5
Citrobacter
-
freundii
Ertapenem
_amoxicillin
_Ceftazidime - clavulanic acid
6
7
Acinetobacte -
ciprofloxacin; _amoxicillin
r baumannii
cefepime;
- clavulanic
ertapenem
acid
piperacillin/
_amoxicillin
tazobactam
- clavulanic
Morganella morganii
acid
Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Data statement
17
Patient data is available in a coded format to ensure privacy of patients.
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2. Chang L, Chia H, ChiuaNC,Huang FY, Lee KS. Deep Neck Infections in Different Age Groups of Children. J Microbiol Immunol Infect. 2010;43(1):47–52
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3. Barratt GE, Koopmann CF Jr, Coulthard SW. Retropharyngeal abscess: a ten-year experience. Laryngoscope. 1984 Apr; 94(4):455-63. 4. Bebell L, Muiru A. Antibiotic use and emerging resistance—how can resource-limited countries turn the tide? Global heart. 2014; 9(3):347-358. doi:10.1016/j.gheart.2014.08.009. 5.
World Health Organization. Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity [Internet]. Apps.who.int. 2019 [cited 19 February 2019]. Available from: http://apps.who.int/iris/handle/10665/85839
6. Songu M, DeMiray U, Adibelli ZH, Adibelli H. Bilateral deep neck space infection in the paediatric age group: a case report and review of the literature. Acta Otorhinolaryngol Ital 2011;31:190-193 7. Lawrence R & Bateman N. Controversies in the management of deep neck space infection in children: an evidence-based review. Clin Otolaryngol. 2017;42: 156–163 8. Coticchia JM, Getnick GS, Yun RD, et al. Age-, site-, and time-specific differences in pediatric deep neck abscesses. Arch Otolaryngol Head Neck Surg. 2004; 130:201–207 9. Thompson J, Cohen S, Reddix P. Retropharyngeal abscess in children: A retrospective and historical analysis. Laryngoscope. 1998;98(6):589-92 10. Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012; 18:268–281 11. Rega AJ, Aziz SR & Ziccardi VB. Microbiology and antibiotic sensitivities of deep neck space infections. Journal of Oral and Maxillofacial Surg. 2004; 62:25-26 12. Yang SW, Lee MH, See LC, Huang SH, Chen TM, Chen TA. Deep neck abscess: an analysis of microbial etiology and the effectiveness of antibiotics. Infect Drug Resist. 2008;1:1–8.
13. Agarwal A, Sethi A, Sethi D, Mrig S, Chopra S. Role of socioeconomic factors in deep neck abscess: A prospective study of 120 patients. British Journal of Oral and Maxillofacial Surgery. 2007;45(7):553555.
14. Rana K, Kumar Rathore P, Wadhwa V, Kumar S. Deep Neck Infections: Continuing Burden in Developing World. International Journal of Phonosurgery & Laryngology. 2013;3:6-9.
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15. WHO Tuberculosis Country Profiles, South Africa. Extranet.who.int. 2018 [cited 19 February 2019]. Available from:
https://extranet.who.int/sree/Reports?op=Replet&name=/WHO_HQ_Reports/G2/PROD/EXT/T BCountryProfile&ISO2=ZA&outtype=PDF (accessed 13 February 2019). 16. MSH. International drug price indicator guide [Internet]. Apps.who.int. 2014 [cited 13 February 2019]. Available from: http://apps.who.int/medicinedocs/documents/s21982en/s21982en.pdf
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S0278-2391(19)31355-2
DOI:
https://doi.org/10.1016/j.joms.2019.11.028
Reference:
YJOMS 58992
To appear in:
Journal of Oral and Maxillofacial Surgery
Received Date: 24 September 2019 Revised Date:
24 November 2019
Accepted Date: 25 November 2019
Please cite this article as: Maharaj S, Mungul S, Ahmed S, Deep Neck Space Infections: Changing trends in Paediatrics versus Adults, Journal of Oral and Maxillofacial Surgery (2020), doi: https:// doi.org/10.1016/j.joms.2019.11.028. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier Inc on behalf of the American Association of Oral and Maxillofacial Surgeons
TITLE PAGE Deep Neck Space Infections: Changing trends in Paediatrics versus Adults Author names and affiliations: Shivesh Maharaj1 Sheetal Mungul 2, Sumaya Ahmed, 3
1)Shivesh Maharaj MBBCH, FCORL, MMED Head of Department Charlotte Maxeke Johannesburg Academic Hospital, School of Neurosciences, Department of Otolaryngology, University of the Witwatersrand, Johannesburg, South Africa. Email: [email protected] 2) Sheetal Mungul MBBCH, BSC( Biomedical science) Registrar Charlotte Maxeke Johannesburg Academic Hospital, School of Neurosciences, Department of Otolaryngology, University of the Witwatersrand, Johannesburg, South Africa. Email: [email protected] 3) Sumaya Ahmed MBBCH, FCORL, MMED Otorhinolaryngologist Department of Otolaryngology, University of the Witwatersrand, Johannesburg, South Africa. Email: [email protected]
Corresponding author: Dr S Maharaj, Academic Head of Department, email: [email protected] Present / Permanent address: Charlotte Maxeke Johannesburg Academic Hospital, School of Neurosciences, Department of Otolaryngology, University of the Witwatersrand, Johannesburg, South Africa Keywords: Deep neck space infection, Microbiology, Antibiotics
TITLE PAGE Deep Neck Space Infections: Changing Trends in Paediatrics versus Adults Author names and affiliations: Shivesh Maharaj1 Sheetal Mungul 2, Sumaya Ahmed, 3 1)Shivesh Maharaj MBBCH, FCORL, MMED Head of Department Charlotte Maxeke Johannesburg Academic Hospital, School of Neurosciences, Department of Otolaryngology, University of the Witwatersrand, Johannesburg, South Africa. Email: [email protected] 2) Sheetal Mungul MBBCH, BSC( Biomedical science) Registrar Charlotte Maxeke Johannesburg Academic Hospital, School of Neurosciences, Department of Otolaryngology, University of the Witwatersrand, Johannesburg, South Africa. Email: [email protected] 3) Sumaya Ahmed MBBCH, FCORL, MMED Otorhinolaryngologist Department of Otolaryngology, University of the Witwatersrand, Johannesburg, South Africa. Email: [email protected]
Corresponding author: Dr S Maharaj, Academic Head of Department, email: [email protected] Present / Permanent address: Charlotte Maxeke Johannesburg Academic Hospital, School of Neurosciences, Department of Otolaryngology, University of the Witwatersrand, Johannesburg, South Africa Keywords: Deep neck space infection, Microbiology, Antibiotics
ABSTRACT
Purpose: To study the clinical presentation and microbiology in patients with deep neck space infection in a developing nation so as to aid in determining relevent, appropriate and effective empiric antimicrobial treatment. To describe the demographics of pediatric verse adult patients affected and the predominant age-related subtypes of deep neck space infections
Methods: A retrospective review of patients with deep neck space infections over a 5,5-year period was conducted at the academic teaching hospitals in Johannesburg, South Africa. Diagnosis of deep neck space infection was determined by clinical, radiographic and laboratory findings. All patients received abscess drainage via either needle aspiration or surgical drainage using a sterile technique. Aerobic and anaerobic bacterial cultures and cultures for Mycobacterium tuberculosis were performed. Results were recorded, and statistical analysis was performed.
Results: A total of 107 children and 52 adults with deep neck space infections were included in the study, with 121 and 70 pus specimens retrieved. The male: female ratio was 1.14:1 for the paediatric group with a total of 53% (n=57) males and 47% (n=50) females. The adult group comprised 63% (n=33) males and 37% (n=19) females. The ratio of males: females was 1.74:1.
In the paediatric group, the mean age was 5.8 years (range 2months – 15years). Age distribution was subcategorized into <2years, 2-10years and >10years 51 patients were < 2 years of age, 50 patients were between 2-10years of age and 6 patients were older than 10years. The age distribution of adult patients ranged from 19 to 77 years, with a mean of 40.9 (+ -15.5) yrs.
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Multi-space involvement of deep neck infection occurred in 7.5% (n=8) of paediatric cases and 59.6% (n=31) of cases in the adult population.The submandibular space was the most common affected site (73.9%) in both groups.
Conclusion: Deep neck space infections differ in clinical presentation and microbiology in adults and paediatrics. The paediatric group predominantly cultured Staph. Aureus, whereas the adult population was mainly polymicrobial. There was a poorer patient outcome in the adult population with a greater number of Intensive Care Unit (ICU) admissions , theatre visits and prolonged hospital stay.
1. INTRODUCTION Deep neck space infection is defined as infection in the potential spaces and fascial planes of the neck 1.
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The anatomical differences in peadiatric and adult neck anatomy lead to different manifestations of the disease process. Pediatric deep neck space infections are a distinct entity from adult deep neck space infections as lymph nodes are more predominant in different anatomical sites in children, resulting in different clinical presentations and inciting pathogens from drainage areas affected 2. The mainstay of treatment currently involves antibiotics and surgical drainage when required. Antimicrobial resistance is currently a critical issue worldwide and a higher pattern of resistance is seen in lower socioeconomic countries, such as those in Sub-saharan Africa 3,4. A comparison of the microbiology of pathogens in pediatric verse adult deep neck space infections has to our knowledge, never been investigated in South Africa before. The purpose of this study is to investigate the spectrum of pathogens and patterns of antibiotic resistance in adult versus paediatric patients with deep neck space infections seen at our tertiary teaching centers. It is hypothesized that although pediatric patients are younger and more at risk of serious complications, that our adult patients with deep neck space infections are in fact more severely affected. It is also expected that an overall higher incidence of antimicrobial resistance is seen in patients from a lower socioeconomic setting and that these pathogens differ between the paediatric and adult population. Our aim is therefore to investigate the differences between paediatric and adult deep neck space infections to gain a better understanding of pathogenesis of disease and guide patient management in a resource constrained setting.
2. METHODS 2.1 A retrospective review of all patients with deep neck space infections, who were admitted to the teaching hospitals affiliated to the University of the Witwatersrand Gauteng, South Africa from the 1 July 2008 to the 30June 2017
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was performed. These spaces include the submandibular, parotid, masticator, peritonsillar, parapharyngeal, retropharyngeal, pretracheal and prevertebral spaces. Patients with superficial skin infection, non-suppurative lymphadenitis and congenital abnormalities were excluded. Patients with non-suppurative lymphadenitis were excluded due to the absence of pus for adequate laboratory testing in our setting, The diagnosis of deep neck space infection was determined by clinical, radiographic and laboratory findings. Most patients were investigated by means of ultrasonography due to cost-effectiveness and, where necessary, a CT scan or MRI was performed. All patients received abscess drainage via either needle aspiration or surgical drainage using a sterile technique. Aerobic and anaerobic bacterial cultures and cultures for Mycobacterium tuberculosis were performed under aseptic field and technique at the National Health Laboratory Service. Patients were treated with empiric intravenous broad-spectrum antimicrobial therapy, which was then culture-directed once microbiology results were available. The results of these pus specimens from the National Health Laboratory Service was evaluated and the following characteristics reviewed: •
The presence or absence of an organism
•
What organism was identified
•
The culture results
•
The antimicrobial sensitivities
•
Additional data such as age, gender, white cell count, differential count, hemoglobin level, platelets, C-reactive protein, albumin level, HIV status and duration of hospitalization were also retrieved when available.
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2.2 Statistical analysis with the Chi-square test was conducted using the Stata statistical program (Stata/IC 14.2 for Windows), to assess differences between patients of different age groups and with different anatomical subtypes of deep neck space infections. A p value of < 0.05 was considered statistically significant. Descriptive statistics such as percentages and frequencies were also used.
3. ETHICS Ethics approval was obtained by the Human Research Ethics Committee, University of the Witwatersrand. All personal and identifying information was kept confidential.
4. RESULTS A total of with 107 children and 52 adults with deep neck space infection were included in the study, respectively with 121 and 70 pus specimens retrieved. The male: female ratio was 1.14:1 for the paediatric group with a total of 53% (n=57) males and 47% (n=50) females. The adult group comprised of 63% (n=33) males and 37% (n=19) females. The ratio of males: females was 1.74:1.
In the paediatric group, the mean age was 5.8 years (range 2months – 15years). Age distribution was subcategorized into <2years, 2-10years and >10years 51 patients were < 2 years of age, 50 patients were between 2-10years of age and 6 patients were older than 10years. The age distribution of adult patients ranged from 19 to 77 years with a mean age of 40.9 (+ -15.5) yrs.
Multi-space involvement of deep neck infection occurred in 7.5% (n=8) of cases of paediatric patients and 65% (n=34) of adult patients. The distribution of neck space involvement in the 159 patients is illustrated in table 1. The submandibular space was the most common
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affected site (73.9% of paediatric patients and 92.3% of adults). The average duration of hospitalization in our study was 5 days for paediatrics and 9 days in adults. The majority of adult patients required admission into the Intensive Care Unit (ICU) at some stage of their treatment and 10 of these adult patients (19%) demised. This subgroup of patients comprised 8 patients who died of overwhelming sepsis and 2 patients who died as a result of comorbid conditions namely dilated cardiomyopathy and renal failure respectively. These patients admitted to ICU had, on average, a longer duration of hospitalization of 19 days verse 7 days for adult patients not requiring ICU care. There was no significant difference in duration of hospitalization in children less than 2 years and children older than 2 years of age (p value 0.13). There was also no age-related difference regarding single space vs multispace infection, with children under 2years and older than 2 years being similarly affected (p value 0.15). There was also no significant difference in duration of hospital stay in patients with single space infection compared to those patients with multi-space deep neck infection (p value 0,103) in the paediatric population. However, the adult population presented with a much higher incidence of multispace involvement and this significantly increased duration of hospitalization as opposed to patients who had single space infection (p value > 0,05). Whereas the sources of paediatric infections were mainly as a result of upper respiratory tract infection, resulting in involvement of a variety of neck spaces, bacterial parotitis, submandibular, submental and parapharyngeal abscesses; there were 2 patients with TB parotitis. One child had TB with multispace involvement and as mirrored in the adult population, buccal, masticator and submandibular space infections occurred in older patients as a result of dental infections. All 159 patients had drainage of the abscess by either needle aspiration or surgical incision and drainage. Only 16 % of paediatric patients (17 patients) were tested for associated HIV infection as a predisposing factor due to the documentation of their status on the road to health card. Testing for HIV infection was therefore only done on the basis of clinical suspicion where the status of the child was uncertain. The prevalence of HIV infection in the adult population was, however, much higher 67% (n=36).
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Laboratory results analysis of the paediatric population showed an average white blood cell count of 21 (x 109L), C-reactive protein of 78 mg/L, hemoglobin level of 11.2 g/dL, platelet count of 504. 57 (x 109L), patients had blood tests for anemia and 46% of these patients were anemic as seen in Table 2. Analysis of the adult population demonstrated an average white blood cell count of 17 (x 109L),, C-reactive protein of 98 mg/L and hemoglobin level of 11 g/dL, with 52% of adult patients being anaemic. 5 In paediatric patients, 97 pus samples were sent for TB microscopy, culture and sensitivity. Only 3 results were positive for TB, and all organisms were sensitive to isoniazid, with one patient having concomitant HIV infection. All of the 52 adult patients had specimens tested for TB and 2 patients were positive. Analysis of the 191 pus specimens demonstrated an identifiable organism in 71% (n=135) of all cases, with no bacterial growth in 29% (n=56) of specimens. (75.5 % identified in paediatric group and 66.5 % in the adult group). Staphylococcus aureus was the most predominant organism cultured in the paediatric group, with a prevalence of 65% of positive pus cultures. 100% of these organisms were sensitive to cloxacillin, and all were resistant to penicillin / ampicillin. This was followed by Streptococcus pyogenes with a prevalence of 5.8%. Streptococcus anginosus, Streptococcus constellatus and coagulase-negative Staphylococcus had an equal prevalence of 3.5% of positive cultures. The incidence of MRSA was 1.2% in our study and only occurred in one paediatric patient. With respect to positive cultures, there was an overall organism sensitivity to cloxacillin of 67% and overall resistance to penicillin / ampicillin of 76% The adult culture results were more diverse, with the majority of organisms being aerobic in nature (n=24), with a smaller incidence of anaerobes (n=2) and TB (n=2), respectively. Extended spectrum beta lactamase producing Klebsiella (ESBL KLESP), Enterobacter cloacae (ENTCL), Serratia marcescens (SERMA), Citrobacter freundii (CITFR) and Morganella morganii (MOGMO), interestingly all gram negative bacilli (GNB), were the 5 of 26 identified microbes (19%) in this study with reported resistance to amoxicillin – clavulanic acid, 7 of 57 microbes (12%) when all pathogens were considered. Recommended alternative antimicrobial
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coverage for these organisms included: Ertapenem effective against MOGMO, CITFR, ENTCL, SERMA and ESBL KLESP; cefepime effective.(table 3)
5. DISCUSSION Deep neck space infection is defined as infection in the potential spaces and fascial planes of the neck, within the confines of the deep layer of cervical fascia1. These infections include lymphadenitis, cellulitis, necrotic nodes and abscesses6. Ear, nose or throat infections may spread to these spaces via contiguous or lymphatic spread and may lead to abscess formation and subsequent life-threatening complications if left untreated2.
These
complications include airway compromise, jugular vein thrombosis, carotid artery aneurysm or rupture, mediastinitis and sepsis 6. It is hypothesized that although pediatric patients are younger and more at risk of these complications, that our adult patients with deep neck space infections are in fact more severely affected. It is also expected that an overall higher incidence of antimicrobial resistance is seen in patients from a lower socioeconomic setting and that these pathogens differ between the paediatric and adult population.
The anatomical spaces deep to the deep layer of cervical fascia of the neck may be divided into those above the hyoid bone, those below it and those that involve the entire length of the neck7. Those above the hyoid bone include the peritonsillar, submandibular, parapharyngeal, masticator, buccal and parotid spaces7. Deep neck spaces below the hyoid bone refer to the anterior visceral / pre-tracheal space and spaces which involve the whole length of the neck include the retropharyngeal, danger, pre-vertebral and carotid spaces respectively 7.
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In our study, there was no age-related difference in the spectrum of deep neck spaces affected in both groups as the submandibular space was the most commonly affected across all ages. It is also evident that although retropharyngeal abscesses are commonly seen in some countries in the younger pediatric population, it is relatively rare in our population as none of the patients presented with retropharyngeal abscesses during our study period.8,9 The incidence of peritonsillar abscess was low in our study due to our inclusion criteria, as only patients with specimens sent for microbiology were evaluated; but it was noted that adults were more affected which is consistent with the literature 2. Contrary to what is seen in other countries where children have delayed presentations due to inability to communicate and are more at risk of serious complications, the converse appears to be true to our population. Adult patients presented with more severe, often lifethreatening infections with multispace involvement, generally dental in aetiology and in some cases as a complication of tonsillitis. This demonstrates that in a lower income environment, caregivers are more vigilant about illness in children, but themselves only present to hospitals in times of absolute need, possibly due to the financial impact that this may have on themselves and their families. Adult patients had nearly double the average duration of hospitalization of their paediatric counterparts. Microbiological studies of patients with deep neck space infections demonstrated that the main inciting organisms are bacterial in origin, but these bacteria may differ in pediatrics to those seen in the adult population 7. This may be because adult deep neck space infections are generally due to dental pathology whereas pediatric deep neck space infections may be due to tonsillitis, pharyngitis, hematogenous spread and suppurative cervical lymphadenitis7. This is evidenced by the spectrum of organism seen in our study as those in paediatric patients were mainly due to Staphylococci whereas the adult culture results reflected flora of the oral cavity. Antimicrobial resistance is currently a worldwide concern and a higher pattern of resistance is seen in lower socioeconomic countries such as those in Sub-Saharan Africa 4. It is defined by Magiorakos et al., 2012 as “the ability of a specific bacterium to survive in the presence of
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an antibiotic that was originally effective to treat infections caused by the bacterium, or acquisition of a specific antibiotic resistance mechanism”10,11,12,13,14. Bacteria may be either intrinsically resistant or may acquire resistant genes from other bacteria that are already resistant 10. Resistance is on the rise for example aerobic bacteria such as Staphylococcus aureus and this places a greater burden on our healthcare system with prolonged hospital admissions, more rapid disease progression, greater morbidity and eventual costs4. Lower-middle income countries have higher resistance patterns and are especially at risk as there are limited resources in terms of the generations of antibiotics readily available, as well as diagnostic challenges which may lead to inappropriate antibiotic use 4. This problem in lower socioeconomic countries is compounded by the limited amount of studies of a reasonable size reporting antimicrobial sensitivity outside of the intensive care setting. HIV infection was present in a much higher proportion of adults as opposed to Paediatric patients as is expected as the paediatric population are usually infected via maternal transmission, whereas adults contract the disease through sexual practice. In the overall 33% patients tested positive for HIV; however, only five of these patients had concomitant TB despite the high level of suspicion in our setting. This demonstrates that despite the national incidence of TB of 60% in patients who are HIV positive, there is a relatively lower incidence of TB in deep neck space infection in our population
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. This may be due to a high
percentage (79%) of household contacts of confirmed TB cases on preventative treatment 15. Nutritional deficiency and compromised immune status affect a wide spectrum of patients, thus affecting various age groups, as reflected in our study. There was a high but similar prevalence of anaemia, which reflects the burden of nutritional deficiency in a lower income country. This affects immune function and hampers the body’s ability to fight infection, which may result in serious complications from conditions such as infections of the aerodigestive tract in patients who might have otherwise recovered given a competent immune system and nutritional status. This problem is compounded by poor access to healthcare in a resource constrained environment where investigations and adequate antimicrobial therapy
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may not be readily available. It is imperative to therefore address these public health issues on a national level in order to dampen the burden on our healthcare system. In addition, access to healthcare and education are key issues which may decrease the incidence of deep neck space infections in patients of lower socioeconomic status. The World Health Organization has issued an international drug price indicator guide which provides objective information about the cost of medication16. The estimated cost of cloxacillin is 0.16 US dollars per day and the estimated cost of amoxicillin-clavulanic acid is 0.18-1.14 US dollars per day 16. Both drugs are beta-lactam antibiotics and the use of cloxacillin in the paediatric population may have not only a beneficial therapeutic effect in our setting but may also have a positive economic impact on healthcare facilities which have limited resources. However, timeout drainage of abscesses in the adult population and the administration of metronidazole may aid in the empiric medical treatment of these patients until culture directed therapy may be initiated. Development of protocols at primary healthcare facilities may also aid in the treatment of patients and limit the rate of complications and duration of hospitalization. Conclusion: Deep neck space infections differ in clinical presentation and microbiology in adults and paediatrics. The paediatric group predominantly cultured Staph aureus whereas the adult population was mainly polymicrobial. There was a poorer patient outcome in the adult population with a greater number of Intensive Care Unit (ICU) admissions , theatre visits and prolonged hospital stay. Futher research may be done in terms of appropriate investigations, surgical verse medical management options and prevention of the deep neck space infection.
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Table 1: Distribution of neck spaces affected by DNSI Deep neck space
No. of cases
Number patients
of Number patients
Age < 2years
Suprahyoid neck space
13
Age years
of Number patients 2-16 Adults
of
Buccal space
5
1
4
0
Masseteric space
1
1
-
0
Masticator space
1
-
1
0
Parotid space
9
6
3
3
Parapharyngeal space
1
1
0
4
Peritonsillar space
1
-
1
10
Submandibular space
85
48
37
31
Submental space
11
8
3
2
Temporal space
1
1
-
0
1
-
1
2
Infrahyoid neck space Posterior cervical space
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Table 2 Study period 1/07/2008 till 30 June 2017
The Wits university teaching hospitals CMJAH and CHB.
Adults> 16 years
Peadiatrics < 16 years
Number of patients:
52
107
Number of specimens
70 specimens and
121 specimens
Gender:
33 males/ 19 females
Micro-organisms
57 males/ 50 females
26 different organisms
Mainly Staph Aureus(70%)
24 aerobic 2 anaerobic
Resistance patterns:
7 resistant to Augmentin
Resistant to penicillin Sensitive to cloxacillin
Average Lab results:
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Average:
Wcc
17 (x 109 L)
Wcc
21 (x 109 L)
CRP
98 mg/L
CRP
78 mg/L
Hb
11 g/dl
Hb
11.2 g/dl
52 sent for TB
97 sent for TB
2 postive for TB
3 positive for TB
Table 3 : Aerobic and Anaerobic Bacteria Resistance and sensivity
Aerobic
1
Anaerobi Antibiotic
Antibiotic
c
resistance
sensitivity
Acinetobacte -
Ciprofloxacin; _amoxicillin
r baumannii
ceftazidime
- clavulanic acid
2
Morganella -
cefepime;
_amoxicillin
morganii
ertapenem
- clavulanic acid
3
16
Enterobacter -
ciprofloxacin; _amoxicillin
cloacae
cefepime;
- clavulanic
ertapenem
acid
Aerobic
4
Serratia
Anaerobi Antibiotic
Antibiotic
c
resistance
sensitivity
-
_amoxicillin
marcescens
- clavulanic acid
5
Citrobacter
-
freundii
Ertapenem
_amoxicillin
_Ceftazidime - clavulanic acid
6
7
Acinetobacte -
ciprofloxacin; _amoxicillin
r baumannii
cefepime;
- clavulanic
ertapenem
acid
piperacillin/
_amoxicillin
tazobactam
- clavulanic
Morganella morganii
acid
Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Data statement
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Patient data is available in a coded format to ensure privacy of patients.
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