gms | German Medical Science

GMS Infectious Diseases

Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG)

ISSN 2195-8831

Calculated parenteral initial treatment of bacterial infections: Infections in the ear, nose, throat and mouth and jaw area

Guideline Calculated parenteral initial therapy

  • corresponding author Bernhard Olzowy - HNO-Zentrum Landsberg am Lech, Germany
  • Bilal Al-Nawas - Klinik für Mund-, Kiefer- und Gesichtschirurgie, Universitätsmedizin Mainz, Germany
  • Miriam Havel - Klinik und Poliklinik für HNO-Heilkunde, Klinikum der Universität München, Munich, Germany
  • Julia Karbach - Klinik für Mund-, Kiefer- und Gesichtschirurgie, Universitätsmedizin Mainz, Germany
  • Rainer Müller - Klinik und Poliklinik für Hals-, Nasen- und Ohrenheilkunde, Universitätsklinikum Carl Gustav Carus Dresden, Germany

GMS Infect Dis 2020;8:Doc14

doi: 10.3205/id000058, urn:nbn:de:0183-id0000589

This is the English version of the article.
The German version can be found at: http://www.egms.de/de/journals/id/2020-8/id000058.shtml

Published: March 26, 2020

© 2020 Olzowy et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Abstract

This is the sixth chapter of the guideline “Calculated initial parenteral treatment of bacterial infections in adults – update 2018” in the 2nd updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience.

The chapter deals with the antibacterial treatment of more severe infections of the ear, the nose, the throat and the maxillofacial region, including odontogenic and salivary gland infections.


Introduction

Bacterial infections of the head and neck region often require the use of antibiotics. The decision for parenteral treatment depends on the severity of the infection, possible risk of spread (for example obstruction of the airways), comorbidities and individual application requirements. In some cases, even in severe infections, the good bioavailability of orally administered fluoroquinolones and clindamycin allows oral administration. This should be given preference as much as possible due to the greater ease of administering it. In contrast, initial treatment of mastoiditis, external otitis maligna, sinusitis with orbital or intracranial complications, epiglottitis, severe odontogenic abscess and cervical phlegmon should generally be with a parenteral antibiotic. As a rule, initial treatment must be calculated; however, in these serious diseases a diagnosis of the microbiological pathogen should be the aim. Sequential therapy is usually possible, i.e. oral treatment after clinical improvement.

The data on oral antibiotic treatment for minor infections of the head and neck region has improved in recent years. For appropriate recommendations, meta-analyzes of numerous randomized comparative studies with large patient populations are to hand. Such studies are rare for severe infections. Since severe infections are relatively uncommon and since there are ethical concerns regarding randomization of forms of treatment in which a statistically significant difference would be expected, an improvement of the data situation cannot to be expected in the medium term. Accordingly, current recommendations are essentially based on the likely pathogen spectrum, the local pathogen resistance situation and the action spectrum of the available antibiotics. Significant regional differences are to be expected with regard to the expected pathogen spectrum – depending on variables such as antibiotic use and vaccination situation. Current studies are scarce on the pathogen spectrum of severe bacterial infections of the head and neck region for the German-speaking countries. The current recommendations of the relevant specialist associations have been taken into account in the following recommendations [1], [2], [3], [4], [5].


Otitis externa maligna and osteomyelitis of the base of the skull

Otitis externa maligna is a rare form of osteomyelitis that typically affects older diabetics and, more rarely, other immunosuppressed patients. It presents clinically as an otitis externa with unusually strong otalgia, otorrhea and granulation in the external auditory canal but cannot be cured with the usual local treatment of ear canal cleaning and antibacterial ear drops. In the process, cranial nerve failure can occur, especially pareses of the facial nerve. Fatal outcomes are recorded [6], [7], [8]. The suspected clinical condition should be clarified by means of CT, bone scintigraphy or MRI and in uncomplicated cases a microbiological diagnosis should be carried out after a 48-hour break of any antimicrobial treatment [9]. The disease is usually caused by Pseudomonas aeruginosa and only rarely by other pathogens [10], [11].

In hospitals, Pseudomonas isolates with a resistance to three or four of the common Pseudomonas-effective classes of antibiotics (3MRGN or 4MRGN) have a significant presence. However, colistin is almost always effective in vitro. In contrast, the resistance situation in Pseudomonas isolates from ear-smears in the outpatient care sector in Germany is relatively favorable. Sensitivity probabilities found during the 2013 PEG resistance study (specifically isolates from ear-smears) for outpatient or inpatient care were as follows: Levofloxacin 88% and 70%, ciprofloxacin 88% and 77%, meropenem 100% and 82%, piperacillin 98% and 84%, cefepime 98% and 90%, ceftazidime 98% and 87%, and colistin 100% and 100% respectively [12], [13].

A recently published meta-analysis of 30 case series concludes that initial combination treatment is superior to monotherapy. The authors recommend – if no relevant resistance is present - ceftazidime and ciprofloxacin for 3 weeks, followed by 3 weeks of ciprofloxacin p.o. as a treatment of choice [11]. In Germany, this combination should therefore be used at least in complicated cases (cranial nerve pareses) as the treatment of choice (recommendation grade B). Alternatively in uncomplicated cases, ceftazidime or piperacillin can be used in monotherapy (recommendation grade C). Initial parenteral monotherapy with a fluoroquinolone should only be considered due to the relatively unfavorable resistance situation for patients with an allergy to beta-lactams. Meropenem has no advantage over ceftazidime or piperacillin regarding Pseudomonas activity. Rather, the spectrum of action is unnecessarily broad. Aminoglycosides are unsuitable because of their limited bone penetration. Despite severe nephrotoxic reactions, colistin was re-approved in Germany in 2012 for parenteral treatment of multidrug-resistant Gram-negative pathogens The use in the context of calculated initial treatment should only be considered in complicated cases for patients with an allergy to beta-lactams, with the dosage adapted to the kidney function (recommendation grade C). Treatment duration should be about 6 weeks. More extensive bone necrosis may require surgical debridement of affected areas [14].

Two recent studies from China and the US report an increasing incidence of osteomyelitis of the lateral and central skull base with only minor pain symptoms and therapy-resistant otorrhea, especially in patients after ear operations but also those without any ear symptoms, in which, in addition to Pseudomonas aeruginosa, Staphylococcus aureus, also in particular MRSA was found as the causative agent [10], [15]. In these rare situations, the standard Pseudomonas antibiotics should be combined with a bone-active MRSA-effective antibiotic, for example linezolid or daptomycin (see chapter 10 [16]) (recommendation grade B).


Mastoiditis

Acute mastoiditis is a relatively common complication of acute or chronic otitis media, in which there is a suppurative liquefaction of the trabeculae in the mastoid. It predominantly occurs in children, recently with an increasing incidence [17]. Only one study on mastoiditis in adults could be identified. The pathogen spectrum corresponds essentially to that of acute or chronic otitis media. In the following, the data on the expected pathogen spectrum in children is presented and extrapolated for the treatment recommendations for adults.

The serious clinical picture of acute mastoiditis should be differentiated from other fluid accumulations in the mastoid, which are also frequently described radiologically as mastoiditis. The diagnosis of acute mastoiditis is clinically based on redness, swelling and pressure pain over the mastoid and the resulting protrusion of the auricle [18]. It is mostly caused by pneumococci [17], [18], [19], [20], [21], [22], [23], [24], [25], [26]. According to studies in Finland and the USA, the introduction of vaccination against pneumococci has only resulted in a short-term lower incidence, followed by a marked increase in pneumococci with reduced susceptibility to antibiotics [20], [23]. Other frequently isolated pathogens are Streptococcus pyogenes, Pseudomonas aeruginosa, Staphylococcus aureus and Haemophilus influenzae [17], [19], [21], [22], [24], [26], [27] and more recently also Fusobacterium necrophorum [21], [28]. In children under two, Streptococcus pneumoniae dominates significantly. Pseudomonas aeruginosa and Fusobacterium necrophorum are almost exclusively isolated in children over the age of two [21], [22]. Pseudomonas aeruginosa, in particular, has to be expected in cases of recurrent otitis, tympanostomy tubes and otorrhea. The clinical progression also seems to be normal [26], [29], so that it seems justifiable in the absence of the mentioned criteria, in the context of an initial calculated antibiotic treatment to drop Pseudomonas-effective antibiotics in favor of antibiotics without Pseudomonas activity. Antibiotic treatment in this case should rely on amoxicillin/clavulanic acid, ampicillin/sulbactam, cefotaxime or ceftriaxone + clindamycin or levofloxacin. If Pseudomonas aeruginosa has also been detected, treatment with ceftazidime + clindamycin, piperacillin/tazobactam or meropenem should be considered. In the presence of a genuine allergy to beta-lactams, the combination ciprofloxacin + clindamycin is an option. A paracentesis accompanied by a microbiological pathogen diagnose, possibly with tympanostomy insert, should be performed. In case of complications, subperiosteal abscess or lack of improvement, an antrotomy or mastoidectomy should be performed [30], [31]. The duration of treatment is 7–10 days.


Epiglottitis

While acute epiglottitis in the period prior to the introduction of the Haemophilus influenzae type B vaccine was primarily a pediatric disease caused by this pathogen, other pathogens are more commonly isolated today and adults are more frequently affected than children [32], [33], [34], [35], [36]. It is usually an acute, severe disease with rapid progression, which usually requires immediate inpatient admission, maybe even intensive care monitoring with the possibility of intubation or tracheostomy due to the risk of airway obstruction. In adults, the disease may be caused by pre-existing cysts, which is associated with more severe outcomes and an increased likelihood of requiring surgical intervention [37], [38]. Since any form of manipulation should be avoided in an emergency situation, pathogen diagnostics are rarely performed. Therefore, statements on the frequency of occurrence of certain pathogens are possible only with reservations. In adults, various types of streptococci dominate, while anaerobes and Haemophilus influenzae type B are isolated less frequently but in relevant frequency, quite often as part of a mixed infection [32], [33], [34], [35]. Individual case reports exist of acute epiglottitis caused by Staphylococcus aureus [39], Haemophilus parainfluenzae [40], Corynebacterium diphtheriae [41], Mycobacterium tuberculosis [42] and meningococci [43]. In addition, acute epiglottitis can also be caused by viruses or have a non-infectious cause. Since this is a life-threatening clinical scenario, the most frequent pathogens should be reliably covered by the calculated antibiotic treatment. Amoxicillin/clavulanic acid or ampicillin/sulbactam should be considered in the main [34], [35]. Alternative treatment options are ceftriaxone or cefotaxime + clindamycin or metronidazole [34], [35] and moxifloxacin. At the same time, high-dose corticosteroids should be administered initially [34], [35].


Auricular perichondritis

Auricular perichondritis is characterized by the spread of acute inflammation of the outer ear to the perichondrium. Possible causes include scratch damage, mechanical trauma (othematoma, otostomy), surgical procedures with exposure of the ear cartilage, frostbite, burns, insect bites and piercing but in more than half of cases no cause can be identified [44]. By far the most common pathogen is Pseudomonas aeruginosa. According to one review, it occurs in 87% of infections following piercing [45]. The second most common pathogen is Staphylococcus aureus, followed by Streptococcus pyogenes and other streptococcal species. In individual cases, Enterobacteriaceae and enterococci have also been isolated [44], [45], [46], [47].

Material should be obtained for microbiological diagnostics before the start of treatment. Carrying out a Gram preparation, the result of which is often available within a few hours, can help prevent the use of antibiotics with an unnecessarily broad spectrum. In case of mild forms of Gram-positive cocci (Staphylococcus aureus, streptococci), ciprofloxacin p.o. should be given; clindamycin may be useful in cases of Gram-negative rods (usually Pseudomonas aeruginosa). More severe forms should be treated primarily parenterally because of the risk of abscess formation resulting in permanent deformation of the pinna. Piperacillin/tazobactam, cefepime + clindamycin and ceftazidime and ceftazidime (recommendation grade B) are the antibiotics of choice for treatment. Antiseptic treatment is also applicable. Ciprofloxacin and levofloxacin should only be used in cases of penicillin allergy due to the significantly higher proportion of fluoroquinolone-resistant strains (recommendation grade B). If there is no response to treatment, this may point to relapsing polychondritis or a resistant strain of Pseudomonas as the cause of the infection or cartilage necrosis requiring surgical debridement. The antibiotic susceptibility rates of Pseudomonas aeruginosa found in the 2013 PEG resistance study for outpatient (specifically ear-derived isolates) or inpatient care were as follows: Levofloxacin 88% and 70%, ciprofloxacin 88% and 77%, meropenem 100% and 82%, piperacillin 98% and 84%, cefepime 98% and 90%, ceftazidime 98% and 87%, and colistin 100% and 100% respectively [12], [13]. Once the antibiogram is available, treatment may possibly be continued orally. An incision is necessary if there is pus accumulation, in case of necroses gentle cartilage removal with best possible preservation of the auricle and possibly plastic reconstruction of the auricle after healing.


Nasal boil

Nasal boil is a painful infection of the hair follicles in the nasal vestibule with phlegmonous spread to the tip of the nose, to the bridge of the nose, to the upper lip and along the bridge of the nose caused by Staphylococcus aureus in the sense of an endogenous infection from colonization of the nasal atrium [48], [49]. A study of the resistance status of the nasopharyngeal Staphylococcus aureus from nine European countries shows an MRSA frequency of 0–2.4% for adults. 5–15% of isolates were resistant to clindamycin [50]. In the 2013 PEG Resistance Study, all Staphylococcus aureus isolates from outpatient care contained 8% MRSA [51].

Outpatient treatment with topical antiseptics or antibiotics is usually sufficient in the case of the frequently occurring mild forms (folliculitis without liquefaction and without significant phlegmonous reaction in the surrounding tissue); if a tendency to spread develops, oral antibiotic treatment can be carried out in addition. If possible, the boil should be lanced. In cases of complicated progression, treatment is carried out intravenously and under inpatient care due to the risk of thrombosis of the angular vein with transmitted sepsis to the cavernous sinus [52]. If possible, antibiotic treatment is carried out with a penicillinase-resistant penicillin or a staphylococcal-effective narrow-spectrum cephalosporin. The antibiotic of choice is cefazolin. Flucloxacillin has a less favorable side-effect profile than cefazolin due to its hepatotoxic side effects [53]. Alternatively, cefuroxime, amoxicillin/clavulanic acid or ampicillin/sulbactam can be used but have an unnecessarily broad action spectrum. Clindamycin is used in patients with a penicillin allergy. If there is no improvement, the presence of MRSA should be investigated. A treatment duration of one week is usually sufficient. Moving to oral sequential therapy quickly is desirable. Suitable antibiotics are cefalexin, doxycycline and clindamycin.


Peritonsillitis and peritonsillar abscess

In peritonitis, inflammation has spread in the connective tissue between a tonsil and the constrictor pharyngeal muscle. Peritonsillar abscess is understood to mean the generally one-sided liquefaction of phlegmonously inflamed peritonsillar tissue with accumulation of pus. Peritonsillar abscesses occur predominantly in young adults and more rarely in children. Clinically, it presents as protrusion of the tonsils accompanied by redness and swelling of the palatal arches. In addition, a uvula edema and jaw clamp may be present.

A review published in 2013 with pooled data from 15 studies published between 1980 and 2012 provides a differentiated view of the probable spectrum of causative pathogen [54]. In the majority of cases, these are mixed infections. The most commonly isolated pathogens in monoinfections were group A streptococci (20–45%, but this may be a low frequency estimate due to prior antibiotic treatment) and fusobacteria (4–55%; the dominant pathogen in three Danish studies, especially among children). In mixed infections presumably especially Streptococci of the Streptococcus anginosus group (Streptococcus intermedius, Streptococcus anginosus and Streptococcus constellatus), which were isolated in up to 51% of cases, play an important role. In monoinfections Staphylococcus aureus, Nocardia asteroids, Haemophilus influenzae, Arcanobacterium haemolyticum and Streptococcus pneumoniae have been isolated occasionally or in isolated cases. In contrast, certain species often isolated in the context of mixed infections, especially Streptococci of the serological group C, Peptostreptococcus and Prevotella spp, are only of secondary importance for the disease process [54]. Subsequent publications, which address the pathogen spectrum, did not reveal many new aspects [55], [56], [57].

With regard to the selection of an adequate antibiotic treatment, two randomized comparative studies are available, both of which show no difference in the clinical course of the disease between the treatment arms. In one study, the efficacy of penicillin compared to penicillin + metronidazole [58] and in the other the efficacy of penicillin compared to ampicillin + sulbactam was tested [59]. However, the significance of both studies is limited because of the small number of cases (n=40 and 42 respectively) and simultaneous abscess drainage. In a non-randomized, prospective observational study with 117 patients after single needle aspiration, following monotherapy with penicillin new surgical intervention was required significantly more often than after monotherapy with amoxicillin/clavulanic acid or cefuroxime + metronidazole (14.7% vs. 4.7%) [60].

Treatment of peritonsillitis is by oral or parenteral antibiotic therapy. Peritonsillar abscesses are treated surgically and combined with peri- and postoperative antibiotic therapy. Whenever possible abscess aspiration, abscess incision and irrigation or abscess tonsillectomy are desirable. The recovered pus should be examined microbiologically [4].

Amoxicillin/clavulanic acid, ampicillin/sulbactam or cefuroxime + metronidazole should be used as first line antibiotics (recommendation grade A). All essential pathogens discussed in the literature as the cause of the disease are hereby covered. As alternatives in case of penicillin allergy, clindamycin or moxifloxacin may be considered (recommendation grade B), with the expectation of likely fusobacteria resistance in 16–25% and 7–53% of cases respectively [61]. A Canadian study reports that 32% of clindamycin-resistant strains were isolated from the streptococcal isolates from peritonsillar abscesses [57], whereas in Germany in 2013 only 3% of the isolates of Streptococcus pyogenes were clindamycin-resistant, according to the PEG resistance study and no resistance to moxifloxacin was found [12]. Cephalosporin monotherapy is not recommended as fusobacteria usually produce cephalosporinase [61]. A rapid change to oral administration of medication should be the target. The duration of treatment is around 5–7 days. In a prospective randomized study with 105 patients who were either treated with benzylpenicillin after abscess tonsillectomy or who discontinued any antibiotic treatment, no difference was found between subjective swallowing and pain scores and the progression of leukocyte count and C-score reactive protein [62] so that in uncomplicated cases after abscess tonsillectomy, immediate discontinuation of antibiotic treatment seems justifiable.


Bacterial sinusitis and its complications

Only in severe cases or without spontaneous healing should acute rhinosinusitis be treated with antibiotics, which are then administered primarily orally (recommendation grade A) [63], [64]. In individual cases, indication for parenteral treatment may exist in patients with severe concomitant diseases, unusually severe progression or in the absence of improvement after oral antibiotic treatment. In such cases differential diagnostics should investigate the possibility of an invasive mycosis or non-infectious disease (such as granulomatous polyangiitis, early stage Wegener’s granulomatosis) and the indication for surgical intervention should be considered. With calculated parenteral antibiotic treatment, the most important causative agents of acute rhinosinusitis – Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes, Staphylococcus aureus and, in the case of a dentogenic cause, also various other streptococci and anaerobes [64] should be covered. In Germany, treatment with amoxicillin/clavulanic acid, ampicillin/sulbactam, cefotaxime or ceftriaxone + clindamycin; or moxifloxacin or, in the case of poorer anaerobic activity, levofloxacin is recommended. In patients with cystic fibrosis [65] and patients undergoing bone marrow transplantation [66], Pseudomonas aeruginosa must be considered a possible pathogen. In these cases, the use of piperacillin/tazobactam, ceftazidime + clindamycin or meropenem makes sense.

The various forms of chronic sinusitis are generally not treated with antibiotics but with topical steroids (recommendation grade A) and nasal irrigation. In the instance of primarily very pronounced cases or those that cannot be treated conservatively, surgical intervention should be considered. In the case of an odontogenic cause, the primary goal should be restoration of the dentogenic source. Concomitant oral antibiotic treatment may be useful in acute exacerbations (grade B recommendation) or with markedly purulent forms. In contrast, parenteral treatment should be reserved for patients with severe comorbidities or unusually severe progression. Since in chronic sinusitis there are numerous species of bacteria which may be the pathogen in question, treatment should be as targeted as possible. Commonly isolated pathogens include Staphylococcus aureus, streptococci, Haemophilus influenzae, various Enterobacteriaceae species (Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Serratia marcescens, Proteus mirabilis), Pseudomonas aeruginosa and anaerobes [67], [68], [69], [70]. In calculated treatment, piperacillin/tazobactam, ceftazidime + clindamycin or levofloxacin or moxifloxacin can be used.

The pathogen spectrum of odontogenic maxillary sinusitis is easier to calculate. Most are mixed infections caused by streptococci and anaerobes. Moraxella spp. and Haemophilus spp. are involved. Calculated treatment, which accompanies source control, is carried out either with amoxicillin/clavulanic acid, ampicillin/sulbactam or clindamycin [70]. In addition to antibiotic treatment – at the latest after disappearance of the acute symptoms – surgical restoration pf the odontogenic cause and possibly closure of a possibly present oral antrum connection is necessary.

With a corresponding risk history, multidrug-resistant pathogens must be expected in acute as well as in chronic sinusitis. In a retrospective study by Stanford University, paranasal sinus smears were analyzed over a period of just over than 20 years. The proportion of Staphylococcus aureus grown from the smears was 7.7%. The proportion of MRSA in the Staphylococcus aureus isolates increased from 1.7% (1990–1999) to 26.8% (2006–2010) [71], which is specific to the US and cannot be translated to Germany. Nevertheless, the use of vancomycin or linezolid in combination with meropenem, ceftazidime or ciprofloxacin should be considered if the risk and condition are severe.

Orbital (60–75%), intracranial (15–20%) and bony complications (5–10%), which occur much more frequently as a result of acute rather than chronic rhinosinusitis, must be treated with parenteral antibiotics [64].

Orbital complications of sinusitis

Orbital complications arise either through direct spread of inflammation through the lamina papyracea or through conduction in the veins. Deviating from the long-standing division according to Chandler, in which preseptal lid phlegmons, orbital cellulitis, subperiosteal abscesses, intraorbital abscesses and septic thrombosis of the cavernous sinus were understood as a stage-related progression [72], the preseptal lid phlegmon and septic thrombosis of the cavernous sinus are understood today as independent entities instead [64].

Pure eyelid phlegmons arise mostly not as a result of sinusitis but much more often in the context of infections of the upper respiratory tract, in dacryoadenitis or skin infections. Immediate assessment by an ophthalmologist is recommended. If proptosis, restriction of bulbus motility and visual disturbances (beginning with loss of red-green discrimination) have been excluded, in cases of low illness severity outpatient treatment with oral antibiotics may be used without resorting to imaging techniques. Severe postseptal infections are much rarer than preseptal eyelid phlegmons (about 80%) with a proportion of about 20% [73], [74]. In case of doubt or in the case of signs of an inflammation of the orbital contents, inpatient admission and parental antibiotic treatment should be initiated immediately and a contrast-enhanced CT or MRI should be performed [64].

The most common pathogens are Staphylococcus aureus, streptococci of the Streptococcus anginosus group and anaerobes. Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae and Eikenella corrodens are rarely but regularly isolated. Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Clostridium perfringens and Arcanobacterium haemolyticum are also isolated [73], [74], [75], [76], [77], [78], [79], [80], [81], [82].

Antimicrobial treatment is initially high-dose with amoxicillin/clavulanic acid, ampicillin/sulbactam (recommendation grade A) or cefotaxime or ceftriaxone + clindamycin (recommendation grade B). In cases of penicillin allergy, combination of ciprofloxacin + clindamycin (recommendation grade B) is an option. Depending on the response to the treatment, changing quickly to oral administration of the medication may be possible [83]. Ciprofloxacin and clindamycin may also be administered orally in selected cases [84]. The duration of antibiotic treatment is about 3 weeks in total.

In general, there is also an indication for surgical intervention with restoration of the sinus source and possibly drainage of orbital abscesses. The obtained material should be microbiologically examined and the treatment continued in a targeted manner. In children younger than 2(–4) without abscess or with small medial abscesses and normal visual acuity who are responding rapidly to antibiotic treatment, conservative treatment alone may be sufficient [64].

Intracranial complications of sinusitis

Epidural and subdural abscesses, meningitis, cerebritis and cerebral abscesses as well as septic thromboses of the superior sagittal sinus or cavernous sinus may occur in sinusitis through direct erosion of the skull base, conduction via diploic veins or by hematogenous scattering. The most common pathogens are streptococci (mainly streptococci of the Streptococcus anginosus group) and anaerobes, more rarely staphylococci [85], [86], [87], [88], [89]. Therapeutically, parenteral treatment with antibiotics, surgical restoration of the affected sinuses and – in the presence of abscesses – neurosurgical abscess drainage, each alongside microbiological pathogen diagnostics, is indicated [5], [64]. Cefotaxime or ceftriaxone, both in combination with metronidazole and linezolid, can be considered as first choice drugs in calculated treatment [5]. Those allergic to beta-lactams may be treated with levofloxacin as an alternative to cefotaxime/ceftriaxone. The duration of treatment is 30–60 days.

Osseous complications of sinusitis, frontal osteomyelitis

Frontal osteomyelitis can occur after acute or chronic sinusitis, dental maxillary infections or after trauma. It occurs primarily in adolescents and is often associated with intracranial complications. The most common pathogens are Staphylococcus aureus, Streptococcus pneumoniae and beta-hemolytic streptococci (of the Streptococcus anginosus group in particular), Haemophilus influenzae and anaerobes. However, infections caused by Pseudomonas aeruginosa, Serratia marcescens, Escherichia coli, Salmonella typhi, Pasteurella multocida or fungi (Aspergillus flavus and Mucor) have also been described [90], [91].

Antimicrobial treatment should be initially high-dose with amoxicillin/clavulanic acid, ampicillin/sulbactam, cefotaxime or ceftriaxone (in combination with clindamycin) or with meropenem. In cases of penicillin allergy, moxifloxacin in combination with clindamycin is used (BEWARE: resistances in staphylococci).

There is also the indication for surgical restoration of the affected frontal sinus and the removal of infested bone regions. Sinus puncture material, surgical drainage secretion and bloods are essential for microbiological examination. Upon receipt, targeted antibiotic treatment should be performed in accordance with the microbiological findings. Treatment takes place over a period of about 6 weeks.


Odontogenic infections with a tendency to spread, possibly with local or systemic complications

Most odontogenic infections can be successfully treated with outpatient surgery without antibiotics. If the infection spreads or in case of patients with risk factors, calculated oral antibiotic treatment may be used [92]. It makes little sense to call for pathogen identification in dental practice in such uncomplicated odontogenic infections [93]. In severe odontogenic infections with a tendency to spread and the risk of local and systemic complications which must be treated parenterally, pathogen identification is indispensable, since in the event of a spread or complication treatment can then be targeted [94], [95], [96]. Mostly streptococci of the oral flora are found, more rarely staphylococci as typical aerobic pathogens, even in closed abscesses. Anaerobic or capnophilic pathogens such as Prevotella spp., Fusobacteria, Bacteroides species, Veillonella and Peptostreptococci are common [97], [98].

The data from most of the few existing studies show that pathogens with low resistance to penicillin and clindamycin are usually found in patients with odontogenic infections who have not been previously treated [94], [99], [100]. However, other authors report a 20% share of penicillin-resistant pathogens [101]. In complicated odontogenic infections in patients who have been previously treated and which require parenteral treatment, in 15–35% of cases penicillinase-producing pathogens were found [102], [103], [104] and in some cases critically high resistance rates to clindamycin of 25–45% [102], [103], [104], [105]. Prior treatment with antibiotics in particular seems to be a risk factor for the occurrence of penicillin-resistant pathogens [106], [107]. For severe odontogenic soft tissue infections that have already been pretreated with antibiotics, a higher proportion of isolates with resistance to penicillin and clindamycin must therefore be expected. From the above data it appears that almost all pathogens in the odontogenic region are sensitive to inhibitor-protected penicillins (such as amoxicillin/clavulanic acid). When assessing the resistance situation, however, one should bear in mind that the pathogenetic role of the identified bacteria has not been clarified. In life-threatening situations, carbapenems are the drug of choice for empirical treatment [101], [108], [109]. If allergy to beta-lactams is present, clindamycin should be used as an established alternative in monotherapy, with the above limitations. Moxifloxacin is another possible alternative [105], [110]. Note in this context the AWMF S3 guideline “Odontogenic infections” (registration number 007-006) [3].


Osteomyelitis of the jaw

The most important forms with a bacterial cause are acute and secondary chronic osteomyelitis (odontogenic infection, pulpal and periodontal infection, infected extraction wounds) with leakage of pus, fistula and sequestration. Accordingly, there is a similar pathogen spectrum compared to odontogenic infections, with a high proportion of polymicrobial infections [111]. Actinomycetes are also often detected [112], [113]. Colonization or infection with multidrug-resistant Gram-positive pathogens has also been described in prolonged antibiotic pretreatment [114], [115]. Acute and secondary chronic osteomyelitis are treated both surgically and with antibiotics. This is to be distinguished from the rarer primary chronic osteomyelitis as a non-pustulant and chronic inflammation of unclear aetiology. In this form of osteomyelitis antibiotics, hyperbaric oxygen therapy, nonsteroidal anti-inflammatory drugs and glucocorticoids are used in addition to surgery [116].

Special forms of osteomyelitis, such as infected osteoradionecrosis or osteomyelitis induced by drugs such as bisphosphonates, corticosteroids and antineoplastic substances, are of particular importance because of their frequency and origin. Although the diseases are not primarily caused by bacteria, the bacterial superinfection almost always requires the most targeted adjuvant treatment possible. Because of the severity of the disease, initial antibiotic treatment is usually intravenous [117]. The pathogen spectrum is also similar to that of odontogenic infections [118].

The principle of osteomyelitis treatment consists of eradication of the source, removal of the infected and necrotic bone and empirical treatment, ideally with a pathogen-specific antibiotic. Because of the protracted progression, parenteral treatment is usually required. PMMA chains containing gentamicin have been used successfully for many years, especially in the chronic form [119]. Adjuvant antimicrobial treatment should consider the anaerobic pathogen spectrum in addition to the commonly isolated staphylococci [120]. Clindamycin or penicillin are recommended, however, after prior treatment pathogens with penicillin resistance are found more frequently [111]. Because of the potentially long and critical progression, pathogen diagnosis should always be sought. Some authors recommend that antibiotics should generally be continued orally for 4–6 weeks after surgery [116].


Cervicofacial actinomycosis

The disease, which usually presents as a mixed infection with the pathogen Actinomyces israeli, can be treated well with antibiotics [121], [122]. Depending on the findings, additional surgery may be necessary. The microbiological findings or at least the histological confirmation of Actinomyces drusen is important. Actinomycetes are typically penicillin-sensitive. Penicillin is often given parenterally initially and then switched to oral therapy. In the case of a penicillin allergy, oral sequential therapy with doxycycline or parenteral administration of clindamycin or a cephalosporin is recommended. The importance of the accompanying obligate anaerobic flora is controversial [122], [123]. As with other chronic inflammations and because of poor penetration into the granulation tissue, treatment must be performed over a long time in high dosage. Data on the duration of treatment have not yet been collected for the cervicofacial form. A duration of up to 6 months is considered in complicated forms. For mild progressions or with sufficient surgical restoration, treatment duration of about 6 weeks is recommended [122].


Sialadenitis

Sialadenitis is a bacterial or viral inflammation of the salivary glands. Sialadenitis often occurs as a superinfection after salivary gland dysfunction. Mostly the submandibular gland is affected. Secretion disorders of the salivary and mucous glands cause an increase in the viscosity of the saliva, which promotes the precipitation of inorganic substances. Saliva stones form, which can promote bacterial colonization and infection; they should be removed in the chronic phase [124]. Acute and chronic forms are distinguished. Sialadenitis in children is often caused by viruses (mostly mumps viruses, Parainfluenzae viruses, CMV), while in adults it is more likely to be caused by bacteria (staphylococci, streptococci and anaerobes). Recent publications have found evidence of an increased incidence of infection by Fusobacterium necrophorum (14%), especially in the presence of peritonsillar abscesses (91%) [125], [126]. Fusobacterium necrophorum can cause the serious clinical presentation of Lemierre syndrome. In the acute phase, in most cases, the focus is on conservative treatment. Because of the general symptoms which are often present, parenteral treatment or surgical relief is often required, which usually requires hospitalization. Serious bacterial infections must be treated parenterally with antibiotics. For mild infections, oral treatment is also possible. Studies from the period 1975–1985 described alpha-hemolytic streptococci and staphylococci as the main pathogens [127], [128], [129]. A recent case report highlights the importance of anaerobes in purulent sialadenitis [128], [129]. There are also recommendations for the use of cephalosporins, which, similar to fluoroquinolones, accumulate in the saliva [130] but their effectiveness against possible anaerobes is limited. The frequent penicillin resistance of sialadenitis pathogen leads to the recommendation to use aminopenicillin in combination with a beta-lactamase inhibitor or clindamycin [128].


Summary of recommendations

Table 1 [Tab. 1] summarizes the treatment recommendations.


Note

This is the sixth chapter of the guideline “Calculated initial parenteral treatment of bacterial infections in adults – update 2018” in the 2nd updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience.


Competing interests

The authors declare that they have no competing interests.


References

1.
Deutsche Gesellschaft für Mund-, Kiefer- und Gesichtschirurgie. Osteomyelitis. Leitlinie. AWMF-Registernummer 007-045. AWMF; 2008.
2.
Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie. Antibiotikatherapie der Infektionen an Kopf und Hals. Leitlinie. AWMF-Registernummer 017-066. AWMF; 2008.
3.
Deutsche Gesellschaft für Mund-Kiefer-Gesichtschirurgie; Deutsche Gesellschaft für Zahn-, Mund- und Kieferheilkunde (DGZMK). Odontogene Infektionen. S3-Leitlinie. AWMF-Registernummer 007-006. 2016. Available from: http://www.awmf.org/uploads/tx_szleitlinien/007-006l_S3_Odontogene_Infektionen_2017-12.pdf External link
4.
Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde; Deutscher Berufsverband der Hals-Nasen-Ohrenärzte; Deutsche Gesellschaft für Kinder- und Jugendmedizin; Deutsche Gesellschaft für Pädiatrische Infektiologie. Therapie entzündlicher Erkrankungen der Gaumenmandeln – Tonsillitis. Leitlinie. AWMF-Registernummer 017/024. Available from: https://www.awmf.org/uploads/tx_szleitlinien/017-024l_S2k_Tonsillitis_Gaumenmandeln_2015-08-verlaengert.pdf External link
5.
Deutsche Gesellschaft für Neurologie. Hirnabzsess. Leitlinie. AWMF-Registernummer 030-108. AWMF; 2016. (Leitlinien für Diagnostik und Therapie in der Neurologie). Available from: http://www.awmf.org/uploads/tx_szleitlinien/030-108l_S1_Hirnabszess_2016-08.pdf External link
6.
Cohen D, Friedman P. The diagnostic criteria of malignant external otitis. J Laryngol Otol. 1987 Mar;101(3):216-21.
7.
Chandler JR. Malignant external otitis. Laryngoscope. 1968 Aug;78(8):1257-94. DOI: 10.1288/00005537-196808000-00002 External link
8.
Chandler JR. Malignant external otitis and osteomyelitis of the base of the skull. Am J Otol. 1989 Mar;10(2):108-10.
9.
Guevara N, Mahdyoun P, Pulcini C, Raffaelli C, Gahide I, Castillo L. Initial management of necrotizing external otitis: errors to avoid. Eur Ann Otorhinolaryngol Head Neck Dis. 2013;130(3):115-21. DOI: 10.1016/j.anorl.2012.04.011 External link
10.
Chen JC, Yeh CF, Shiao AS, Tu TY. Temporal bone osteomyelitis: the relationship with malignant otitis externa, the diagnostic dilemma, and changing trends. ScientificWorldJournal. 2014;2014:591714. DOI: 10.1155/2014/591714 External link
11.
Pulcini C, Mahdyoun P, Cua E, Gahide I, Castillo L, Guevara N. Antibiotic therapy in necrotising external otitis: case series of 32 patients and review of the literature. Eur J Clin Microbiol Infect Dis. 2012 Dec;31(12):3287-94. DOI: 10.1007/s10096-012-1694-7 External link
12.
Kresken M, Hafner D, Körber-Irrgang B. Resistenzsituation bei klinisch wichtigen Infektionserregern aus dem ambulanten Versorgungsbereich gegenüber Antibiotika – Bericht über die Ergebnisse einer multizentrischen Studie der Arbeitsgemeinschaft Empfindlichkeitsprüfungen & Resistenz der Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. aus dem Jahre 2010. Abschlussbericht – Teilprojekt N. Rheinbach: Antiinfectives Intelligence; 2013. Available from: https://www.p-e-g.org/files/content/Service/Resistenzdaten/PEG-Resistenzstudie_2010_N.pdf External link
13.
Kresken M, Hafner D, Körber-Irrgang B. Epidemiologie und Resistenzsituation bei klinisch wichtigen Infektionserregern aus dem Hospitalbereich gegenüber Antibiotika – Bericht über die Ergebnisse einer multizentrischen Studie der Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. aus dem Jahre 2010. Abschlussbericht – Teilprojekt H. Rheinbach: Antiinfectives Intelligence; 2013. Available from: https://www.p-e-g.org/files/content/Service/Resistenzdaten/PEG-Resistenzstudie_2010_H.pdf External link
14.
Karaman E, Yilmaz M, Ibrahimov M, Haciyev Y, Enver O. Malignant otitis externa. J Craniofac Surg. 2012 Nov;23(6):1748-51. DOI: 10.1097/SCS.0b013e31825e4d9a External link
15.
Johnson AK, Batra PS. Central skull base osteomyelitis: an emerging clinical entity. Laryngoscope. 2014 May;124(5):1083-7. DOI: 10.1002/lary.24440 External link
16.
Vossen MG, Gattringer R, Thalhammer F, Militz M, Hischebeth G. Kalkulierte parenterale Initialtherapie bakterieller Infektionen: Knochen- und Gelenkinfektionen [Calculated parenteral initial treatment of bacterial infections: Bone and joint infections]. GMS Infect Dis. 2020;8:Doc10. DOI: 10.3205/id000054 External link
17.
Benito MB, Gorricho BP. Acute mastoiditis: increase in the incidence and complications. Int J Pediatr Otorhinolaryngol. 2007 Jul;71(7):1007-11. DOI: 10.1016/j.ijporl.2007.02.014 External link
18.
van den Aardweg MT, Rovers MM, de Ru JA, Albers FW, Schilder AG. A systematic review of diagnostic criteria for acute mastoiditis in children. Otol Neurotol. 2008 Sep;29(6):751-7. DOI: 10.1097/MAO.0b013e31817f736b External link
19.
Amir AZ, Pomp R, Amir J. Changes in acute mastoiditis in a single pediatric tertiary medical center: our experience during 2008-2009 compared with data for 1983-2007. Scand J Infect Dis. 2014 Jan;46(1):9-13. DOI: 10.3109/00365548.2013.849814 External link
20.
Daniel M, Gautam S, Scrivener TA, Meller C, Levin B, Curotta J. What effect has pneumococcal vaccination had on acute mastoiditis? J Laryngol Otol. 2013 Jan;127 Suppl 1:S30-4. DOI: 10.1017/S0022215112002654 External link
21.
Gorphe P, de Barros A, Choussy O, Dehesdin D, Marie JP. Acute mastoiditis in children: 10 years experience in a French tertiary university referral center. Eur Arch Otorhinolaryngol. 2012 Feb;269(2):455-60. DOI: 10.1007/s00405-011-1667-y External link
22.
Groth A, Enoksson F, Hultcrantz M, Stalfors J, Stenfeldt K, Hermansson A. Acute mastoiditis in children aged 0-16 years – a national study of 678 cases in Sweden comparing different age groups. Int J Pediatr Otorhinolaryngol. 2012 Oct;76(10):1494-500. DOI: 10.1016/j.ijporl.2012.07.002 External link
23.
Halgrimson WR, Chan KH, Abzug MJ, Perkins JN, Carosone-Link P, Simões EA. Incidence of acute mastoiditis in Colorado children in the pneumococcal conjugate vaccine era. Pediatr Infect Dis J. 2014 May;33(5):453-7. DOI: 10.1097/INF.0000000000000138 External link
24.
Michalski G, Hocke T, Hoffmann K, Esser D. Die Mastoiditis als Folge einer akuten Otitis media - Eine retrospektive Studie [Therapy of acute mastoiditis]. Laryngorhinootologie. 2002 Dec;81(12):857-60. DOI: 10.1055/s-2002-36098 External link
25.
Mross-Adam C, Klemm E. Die akute Mastoiditis im Kindesalter, eine Analyse des eigenen Krankengutes über 25 Jahre [Acute mastoiditis in children, a retrospective analysis about a period of 25 years]. Laryngorhinootologie. 2005 Jul;84(7):497-502. DOI: 10.1055/s-2005-861376 External link
26.
Laulajainen-Hongisto A, Saat R, Lempinen L, Markkola A, Aarnisalo AA, Jero J. Bacteriology in relation to clinical findings and treatment of acute mastoiditis in children. Int J Pediatr Otorhinolaryngol. 2014 Dec;78(12):2072-8. DOI: 10.1016/j.ijporl.2014.09.007 External link
27.
Migirov L, Kronenberg J. Bacteriology of mastoid subperiosteal abscess in children. Acta Otolaryngol. 2004 Jan;124(1):23-5. DOI: 10.1080/00016480310015380 External link
28.
Le Monnier A, Jamet A, Carbonnelle E, Barthod G, Moumile K, Lesage F, Zahar JR, Mannach Y, Berche P, Couloigner V. Fusobacterium necrophorum middle ear infections in children and related complications: report of 25 cases and literature review. Pediatr Infect Dis J. 2008 Jul;27(7):613-7. DOI: 10.1097/INF.0b013e318169035e External link
29.
Butbul-Aviel Y, Miron D, Halevy R, Koren A, Sakran W. Acute mastoiditis in children: Pseudomonas aeruginosa as a leading pathogen. Int J Pediatr Otorhinolaryngol. 2003 Mar;67(3):277-81. DOI: 10.1016/S0165-5876(02)00388-9 External link
30.
Minovi A, Dazert S. Diseases of the middle ear in childhood. GMS Curr Top Otorhinolaryngol Head Neck Surg. 2014 Dec 1;13:Doc11. DOI: 10.3205/cto000114 External link
31.
Psarommatis IM, Voudouris C, Douros K, Giannakopoulos P, Bairamis T, Carabinos C. Algorithmic management of pediatric acute mastoiditis. Int J Pediatr Otorhinolaryngol. 2012;76(6):791-6. DOI: 10.1016/j.ijporl.2012.02.042 External link
32.
Bizaki AJ, Numminen J, Vasama JP, Laranne J, Rautiainen M. Acute supraglottitis in adults in Finland: review and analysis of 308 cases. Laryngoscope. 2011 Oct;121(10):2107-13. DOI: 10.1002/lary.22147 External link
33.
Briem B, Thorvardsson O, Petersen H. Acute epiglottitis in Iceland 1983-2005. Auris Nasus Larynx. 2009 Feb;36(1):46-52. DOI: 10.1016/j.anl.2008.03.012 External link
34.
Chroboczek T, Cour M, Hernu R, Baudry T, Bohé J, Piriou V, Allaouchiche B, Disant F, Argaud L. Long-term outcome of critically ill adult patients with acute epiglottitis. PLoS One. 2015 May 6;10(5):e0125736. DOI: 10.1371/journal.pone.0125736 External link
35.
Guardiani E, Bliss M, Harley E. Supraglottitis in the era following widespread immunization against Haemophilus influenzae type B: evolving principles in diagnosis and management. Laryngoscope. 2010 Nov;120(11):2183-8. DOI: 10.1002/lary.21083 External link
36.
Wood N, Menzies R, McIntyre P. Epiglottitis in Sydney before and after the introduction of vaccination against Haemophilus influenzae type b disease. Intern Med J. 2005 Sep;35(9):530-5. DOI: 10.1111/j.1445-5994.2005.00909.x External link
37.
Suzuki S, Yasunaga H, Matsui H, Fushimi K, Yamasoba T. Factors associated with severe epiglottitis in adults: Analysis of a Japanese inpatient database. Laryngoscope. 2015 Sep;125(9):2072-8. DOI: 10.1002/lary.25114 External link
38.
Yoon TM, Choi JO, Lim SC, Lee JK. The incidence of epiglottic cysts in a cohort of adults with acute epiglottitis. Clin Otolaryngol. 2010 Feb;35(1):18-24. DOI: 10.1111/j.1749-4486.2009.02069.x External link
39.
Harris C, Sharkey L, Koshy G, Simler N, Karas JA. A rare case of acute epiglottitis due to Staphylococcus aureus in an adult. Infect Dis Rep. 2012 Jan 2;4(1):e3. DOI: 10.4081/idr.2012.e3 External link
40.
Juul ML, Johansen HK, Homøe P. [Epiglottitis with an abscess caused by Haemophilus parainfluenzae]. Ugeskr Laeger. 2014 Mar 17;176(12A). pii: V11130683.
41.
Lake JA, Ehrhardt MJ, Suchi M, Chun RH, Willoughby RE. A Case of Necrotizing Epiglottitis Due to Nontoxigenic Corynebacterium diphtheriae. Pediatrics. 2015 Jul;136(1):e242-5. DOI: 10.1542/peds.2014-3157 External link
42.
El Beltagi AH, Khera PS, Alrabiah L, Al Shammari NF. Case Report: Acute tuberculous laryngitis presenting as acute epiglottitis. Indian J Radiol Imaging. 2011 Oct;21(4):284-6. DOI: 10.4103/0971-3026.90690 External link
43.
Richardson DK, Helderman T, Lovett PB, Lovett P. Meningococcal epiglottitis in a diabetic adult patient: a case report. J Emerg Med. 2012 Oct;43(4):634-6. DOI: 10.1016/j.jemermed.2010.05.025 External link
44.
Davidi E, Paz A, Duchman H, Luntz M, Potasman I. Perichondritis of the auricle: analysis of 114 cases. Isr Med Assoc J. 2011 Jan;13(1):21-4.
45.
Sosin M, Weissler JM, Pulcrano M, Rodriguez ED. Transcarti- laginous ear piercing and infectious complications: a systematic review and critical analysis of outcomes. Laryngoscope. 2015 Aug;125(8):1827-34. DOI: 10.1002/lary.25238 External link
46.
Mitchell S, Ditta K, Minhas S, Dezso A. Pinna abscesses: can we manage them better? A case series and review of the literature. Eur Arch Otorhinolaryngol. 2015 Nov;272(11):3163-7. DOI: 10.1007/s00405-014-3346-2 External link
47.
Prasad HK, Sreedharan S, Prasad HS, Meyyappan MH, Harsha KS. Perichondritis of the auricle and its management. J Laryngol Otol. 2007; 121(6):530-4. DOI: 10.1017/S0022215107005877 External link
48.
Dahle KW, Sontheimer RD. The Rudolph sign of nasal vestibular furunculosis: questions raised by this common but under-recognized nasal mucocutaneous disorder. Dermatol Online J. 2012 Mar;18(3):6.
49.
Shul’ga IA, Deriabin DG, Bukharin OV. Rol’ mikroorganizmov roda Staphylococcus v vozniknovenii i razvitii furunkula nosa [The role of microorganisms in the genus Staphylococcus in the origin and development of nasal furuncles]. Vestn Otorinolaringol. 1994 Mar-Apr;(2):23-5.
50.
van Bijnen EM, Paget WJ, den Heijer CD, Stobberingh EE, Bruggeman CA, Schellevis FG; APRES Study Team. Primary care treatment guidelines for skin infections in Europe: congruence with antimicrobial resistance found in commensal Staphylococcus aureus in the community. BMC Fam Pract. 2014 Oct;15:175. DOI: 10.1186/s12875-014-0175-8 External link
51.
Körber-Irrgang B. Ergebnisse der PEG Resistenzstudie 2013 – Resistenzsituation im ambulanten Versorgungsbereich [Präsentation]. In: Bad Honnef-Symposium; 2015 Mar 30-31; Königswinter. Available from: http://www.peg-symposien.org/tl_files/symposien/symposium_2015/bad_honnef_symposium_2015/gallery/Koerber-Irrgang.pdf External link
52.
Turner AL, Reynolds FE. Furuncle of the Right Nasal Vestibule; Septic Thrombosis of the Cavernous Sinus; Lepto-Meningitis; Death; Autopsy. (With Microscopic Examination of the Orbits, Cavernous Blood Sinuses, Meninges, Ethmoidal and Sphenoidal Air Sinuses). Proc R Soc Med. 1926;19(Laryngol Sect):10.
53.
Andrews E, Daly AK. Flucloxacillin-induced liver injury. Toxicology. 2008 Dec 30;254(3):158-63. DOI: 10.1016/j.tox.2008.08.009 External link
54.
Powell EL, Powell J, Samuel JR, Wilson JA. A review of the pathogenesis of adult peritonsillar abscess: time for a re-evaluation. J Antimicrob Chemother. 2013 Sep;68(9):1941-50. DOI: 10.1093/jac/dkt128 External link
55.
Mazur E, Czerwińska E, Korona-Głowniak I, Grochowalska A, Kozioł-Montewka M. Epidemiology, clinical history and micro- biology of peritonsillar abscess. Eur J Clin Microbiol Infect Dis. 2015 Mar;34(3):549-54. DOI: 10.1007/s10096-014-2260-2 External link
56.
Plum AW, Mortelliti AJ, Walsh RE. Microbial Flora and Antibiotic Resistance in Peritonsillar Abscesses in Upstate New York. Ann Otol Rhinol Laryngol. 2015 Nov;124(11):875-80. DOI: 10.1177/0003489415589364 External link
57.
Sowerby LJ, Hussain Z, Husein M. The epidemiology, antibiotic resistance and post-discharge course of peritonsillar abscesses in London, Ontario. J Otolaryngol Head Neck Surg. 2013 Jan;42:5. DOI: 10.1186/1916-0216-42-5 External link
58.
Tunér K, Nord CE. Impact on peritonsillar infections and microflora of phenoxymethylpenicillin alone versus phenoxymethylpenicillin in combination with metronidazole. Infection. 1986 May-Jun;14(3):129-33. DOI: 10.1007/BF01643477 External link
59.
Yilmaz T, Unal OF, Figen G, Akyol MU, Ayas K. A comparison of procaine penicillin with sulbactam-ampicillin in the treatment of peritonsillar abscesses. Eur Arch Otorhinolaryngol. 1998;255(3):163-5.
60.
Shaul C, Koslowsky B, Rodriguez M, Schwarz Y, Muahnna N, Peleg U, Sichel JY. Is Needle Aspiration for Peritonsillar Abscess Still as Good as We Think? A Long-term Follow-up. Ann Otol Rhinol Laryngol. 2015 Apr;124(4):299-304. DOI: 10.1177/0003489414556083 External link
61.
Brook I, Wexler HM, Goldstein EJ. Antianaerobic antimicrobials: spectrum and susceptibility testing. Clin Microbiol Rev. 2013 Jul;26(3):526-46. DOI: 10.1128/CMR.00086-12 External link
62.
Knipping S, Löwe S, Lautenschläger C, Schrom T. Ist eine begleitende Antibiotikatherapie nach Abszesstonsillektomie erforderlich [Is postoperative antibiotic treatment mandatory after abscess tonsillectomy]. HNO. 2009 Mar;57(3):230-8. DOI: 10.1007/s00106-008-1777-z External link
63.
Chow AW, Benninger MS, Brook I, Brozek JL, Goldstein EJ, Hicks LA, Pankey GA, Seleznick M, Volturo G, Wald ER, File TM Jr; Infectious Diseases Society of America. IDSA clinical practice guideline for acute bacterial rhinosinusitis in children and adults. Clin Infect Dis. 2012 Apr;54(8):e72-e112. DOI: 10.1093/cid/cir1043 External link
64.
Fokkens WJ, Lund VJ, Mullol J, Bachert C, Alobid I, Baroody F, Cohen N, Cervin A, Douglas R, Gevaert P, Georgalas C, Goossens H, Harvey R, Hellings P, Hopkins C, Jones N, Joos G, Kalogjera L, Kern B, Kowalski M, Price D, Riechelmann H, Schlosser R, Senior B, Thomas M, Toskala E, Voegels R, Wang de Y, Wormald PJ. EPOS 2012: European position paper on rhinosinusitis and nasal polyps 2012. A summary for otorhinolaryngologists. Rhinology. 2012 Mar;50(1):1-12. DOI: 10.4193/Rhino50E2 External link
65.
Godoy JM, Godoy AN, Ribalta G, Largo I. Bacterial pattern in chronic sinusitis and cystic fibrosis. Otolaryngol Head Neck Surg. 2011 Oct;145(4):673-6. DOI: 10.1177/0194599811407279 External link
66.
Imamura R, Voegels R, Sperandio F, Sennes LU, Silva R, Butugan O, Miniti A. Microbiology of sinusitis in patients undergoing bone marrow transplantation. Otolaryngol Head Neck Surg. 1999 Feb;120(2):279-82. DOI: 10.1016/S0194-5998(99)70421-3 External link
67.
Brook I. Microbiology of sinusitis. Proc Am Thorac Soc. 2011 Mar;8(1):90-100. DOI: 10.1513/pats.201006-038RN External link
68.
Finegold SM, Flynn MJ, Rose FV, Jousimies-Somer H, Jakielaszek C, McTeague M, Wexler HM, Berkowitz E, Wynne B. Bacteriologic findings associated with chronic bacterial maxillary sinusitis in adults. Clin Infect Dis. 2002 Aug;35(4):428-33. DOI: 10.1086/341899 External link
69.
Genoway KA, Philpott CM, Javer AR. Pathogen yield and antimicrobial resistance patterns of chronic rhinosinusitis patients presenting to a tertiary rhinology centre. J Otolaryngol Head Neck Surg. 2011; 40(3):232-7.
70.
Puglisi S, Privitera S, Maiolino L, Serra A, Garotta M, Blandino G, Speciale A. Bacteriological findings and antimicrobial resistance in odontogenic and non-odontogenic chronic maxillary sinusitis. J Med Microbiol. 2011 Sep;60(Pt 9):1353-9. DOI: 10.1099/jmm.0.031476-0 External link
71.
Rujanavej V, Soudry E, Banaei N, Baron EJ, Hwang PH, Nayak JV. Trends in incidence and susceptibility among methicillin-resistant Staphylococcus aureus isolated from intranasal cultures associated with rhinosinusitis. Am J Rhinol Allergy. 2013 Mar-Apr;27(2):134-7. DOI: 10.2500/ajra.2013.27.3858 External link
72.
Chandler JR, Langenbrunner DJ, Stevens ER. The pathogenesis of orbital complications in acute sinusitis. Laryngoscope. 1970 Sep;80(9):1414-28. DOI: 10.1288/00005537-197009000-00007 External link
73.
Fanella S, Singer A, Embree J. Presentation and management of pediatric orbital cellulitis. Can J Infect Dis Med Microbiol. 2011 Fall;22(3):97-100. DOI: 10.1155/2011/626809 External link
74.
Georgakopoulos CD, Eliopoulou MI, Stasinos S, Exarchou A, Pharmakakis N, Varvarigou A. Periorbital and orbital cellulitis: a 10-year review of hospitalized children. Eur J Ophthalmol. 2010 Nov-Dec;20(6):1066-72.
75.
Erickson BP, Lee WW. Orbital Cellulitis and Subperiosteal Abscess: A 5-year Outcomes Analysis. Orbit. 2015;34(3):115-20. DOI: 10.3109/01676830.2014.950286 External link
76.
Liao JC, Harris GJ. Subperiosteal abscess of the orbit: evolving pathogens and the therapeutic protocol. Ophthalmology. 2015 Mar;122(3):639-47. DOI: 10.1016/j.ophtha.2014.09.009 External link
77.
Murphy C, Livingstone I, Foot B, Murgatroyd H, MacEwen CJ. Orbital cellulitis in Scotland: current incidence, aetiology, management and outcomes. Br J Ophthalmol. 2014 Nov;98(11):1575-8. DOI: 10.1136/bjophthalmol-2014-305222 External link
78.
Peña MT, Preciado D, Orestes M, Choi S. Orbital complications of acute sinusitis: changes in the post-pneumococcal vaccine era. JAMA Otolaryngol Head Neck Surg. 2013 Mar;139(3):223-7. DOI: 10.1001/jamaoto.2013.1703 External link
79.
Ramey NA, Burkat CN. Arcanobacterium hemolyticum orbital cellulitis: a rare but aggressive disease. Ophthal Plast Reconstr Surg. 2013 May-Jun;29(3):e69-72. DOI: 10.1097/IOP.0b013e318272d480 External link
80.
Seltz LB, Smith J, Durairaj VD, Enzenauer R, Todd J. Microbiology and antibiotic management of orbital cellulitis. Pediatrics. 2011 Mar;127(3):e566-72. DOI: 10.1542/peds.2010-2117 External link
81.
Liao S, Durand ML, Cunningham MJ. Sinogenic orbital and subperiosteal abscesses: microbiology and methicillin-resistant Staphylococcus aureus incidence. Otolaryngol Head Neck Surg. 2010 Sep;143(3):392-6. DOI: 10.1016/j.otohns.2010.06.818 External link
82.
Sharma A, Liu ES, Le TD, Adatia FA, Buncic JR, Blaser S, Richardson S. Pediatric orbital cellulitis in the Haemophilus influenzae vaccine era. J AAPOS. 2015; 19(3):206-10. DOI: 10.1016/j.jaapos.2015.02.004 External link
83.
Emmett Hurley P, Harris GJ. Subperiosteal abscess of the orbit: duration of intravenous antibiotic therapy in nonsurgical cases. Ophthal Plast Reconstr Surg. 2012 Jan-Feb;28(1):22-6. DOI: 10.1097/IOP.0b013e31822ddddc External link
84.
Cannon PS, Mc Keag D, Radford R, Ataullah S, Leatherbarrow B. Our experience using primary oral antibiotics in the management of orbital cellulitis in a tertiary referral centre. Eye (Lond). 2009 Mar;23(3):612-5. DOI: 10.1038/eye.2008.44 External link
85.
Deutschmann MW, Livingstone D, Cho JJ, Vanderkooi OG, Brookes JT. The significance of Streptococcus anginosus group in intracranial complications of pediatric rhinosinusitis. JAMA Otolaryngol Head Neck Surg. 2013 Feb;139(2):157-60. DOI: 10.1001/jamaoto.2013.1369 External link
86.
Gallagher RM, Gross CW, Phillips CD. Suppurative intracranial complications of sinusitis. Laryngoscope. 1998 Nov;108(11 Pt 1):1635-42. DOI: 10.1097/00005537-199811000-00009 External link
87.
Kombogiorgas D, Seth R, Athwal R, Modha J, Singh J. Suppurative intracranial complications of sinusitis in adolescence. Single institute experience and review of literature. Br J Neurosurg. 2007 Dec;21(6):603-9. DOI: 10.1080/02688690701552856 External link
88.
Maniglia AJ, Goodwin WJ, Arnold JE, Ganz E. Intracranial abscesses secondary to nasal, sinus, and orbital infections in adults and children. Arch Otolaryngol Head Neck Surg. 1989 Dec;115(12):1424-9. DOI: 10.1001/archotol.1989.01860360026011 External link
89.
Patel AP, Masterson L, Deutsch CJ, Scoffings DJ, Fish BM. Management and outcomes in children with sinogenic intracranial abscesses. Int J Pediatr Otorhinolaryngol. 2015;79(6):868-73. DOI: 10.1016/j.ijporl.2015.03.020 External link
90.
Akiyama K, Karaki M, Mori N. Evaluation of adult Pott’s puffy tumor: our five cases and 27 literature cases. Laryngoscope. 2012 Nov;122(11):2382-8. DOI: 10.1002/lary.23490 External link
91.
Skomro R, McClean KL. Frontal osteomyelitis (Pott’s puffy tumour) associated with Pasteurella multocida-A case report and review of the literature. Can J Infect Dis. 1998 Mar;9(2):115-21. DOI: 10.1155/1998/457984 External link
92.
Cachovan G, Phark JH, Schön G, Pohlenz P, Platzer U. Odontogenic infections: an 8-year epidemiologic analysis in a dental emergency outpatient care unit. Acta Odontol Scand. 2013 May-Jul;71(3-4):518-24. DOI: 10.3109/00016357.2012.696694 External link
93.
Farmahan S, Tuopar D, Ameerally PJ. The clinical relevance of microbiology specimens in head and neck space infections of odontogenic origin. Br J Oral Maxillofac Surg. 2014 Sep;52(7):629-31. DOI: 10.1016/j.bjoms.2014.02.027 External link
94.
Eckert AW, Just L, Wilhelms D, Schubert J. Odontogene Infektionen - Teil I : Zur Wertigkeit der Erregerbestimmung bei odontogenen Infektionen in der klinischen Routine [Dentogenic infections-part I: the significance of bacterial isolation of dentogenic infections under routineous conditions]. Wien Med Wochenschr. 2012 Jul;162(13-14):316-20. DOI: 10.1007/s10354-012-0103-2 External link
95.
Tavakoli M, Bagheri A, Faraz M, Salehirad S, Roghaee S. Orbital cellulitis as a complication of mandibular odontogenic infection. Ophthal Plast Reconstr Surg. 2013 Jan-Feb;29(1):e5-7. DOI: 10.1097/IOP.0b013e318254132a External link
96.
Opitz D, Camerer C, Camerer DM, Raguse JD, Menneking H, Hoffmeister B, Adolphs N. Incidence and management of severe odontogenic infections-a retrospective analysis from 2004 to 2011. J Craniomaxillofac Surg. 2015 Mar;43(2):285-9. DOI: 10.1016/j.jcms.2014.12.002 External link
97.
Bahl R, Sandhu S, Singh K, Sahai N, Gupta M. Odontogenic infections: Microbiology and management. Contemp Clin Dent. 2014 Jul;5(3):307-11. DOI: 10.4103/0976-237X.137921 External link
98.
Walia IS, Borle RM, Mehendiratta D, Yadav AO. Microbiology and antibiotic sensitivity of head and neck space infections of odontogenic origin. J Maxillofac Oral Surg. 2014 Mar;13(1):16-21. DOI: 10.1007/s12663-012-0455-6 External link
99.
Eckert AW, Maurer P, Wilhelms D, Schubert J. Keimspektren und Antibiotika bei odontogenen Infektionen. Renaissance der Penicilline [Bacterial spectra and antibiotics in odontogenic infections. Renaissance of the penicillins?]. Mund Kiefer Gesichtschir. 2005 Nov;9(6):377-83. DOI: 10.1007/s10006-005-0646-0 External link
100.
Eckert AW, Maurer P, Wilhelms D, Schubert J. Weichteilinfektionen in der Mund-, Kiefer- und Plastischen Gesichtschirurgie. Keimspektren und Antibiotika [Soft tissue infections in oral, maxillofacial, and plastic surgery. Bacterial spectra and antibiotics]. Mund Kiefer Gesichtschir. 2005 Nov;9(6):389-95. DOI: 10.1007/s10006-005-0645-1 External link
101.
Fating NS, Saikrishna D, Vijay Kumar GS, Shetty SK, Raghavendra Rao M. Detection of Bacterial Flora in Orofacial Space Infections and Their Antibiotic Sensitivity Profile. J Maxillofac Oral Surg. 2014 Dec;13(4):525-32. DOI: 10.1007/s12663-013-0575-7 External link
102.
Eick S, Pfister W, Straube E. Antimicrobial susceptibility of anaerobic and capnophilic bacteria isolated from odontogenic abscesses and rapidly progressive periodontitis. Int J Antimicrob Agents. 1999; 12(1):41-6. DOI: 10.1016/S0924-8579(99) 00056-4 External link
103.
Kuriyama T, Karasawa T, Nakagawa K, Yamamoto E, Nakamura S. Incidence of beta-lactamase production and antimicrobial susceptibility of anaerobic gram-negative rods isolated from pus specimens of orofacial odontogenic infections. Oral Microbiol Immunol. 2001 Feb;16(1):10-5. DOI: 10.1034/j.1399-302x.2001.160102.x External link
104.
Sobottka I, Cachovan G, Stürenburg E, Ahlers MO, Laufs R, Platzer U, Mack D. In vitro activity of moxifloxacin against bacteria isolated from odontogenic abscesses. Antimicrob Agents Chemother. 2002 Dec;46(12):4019-21. DOI: 10.1128/AAC.46.12.4019-4021.2002 External link
105.
Al-Nawas B, Walter C, Morbach T, Seitner N, Siegel E, Maeurer M, Krummenauer F. Clinical and microbiological efficacy of moxifloxacin versus amoxicillin/clavulanic acid in severe odontogenic abscesses: a pilot study. Eur J Clin Microbiol Infect Dis. 2009 Jan;28(1):75-82. DOI: 10.1007/s10096-008-0587-2 External link
106.
Al-Nawas B, Maeurer M. Severe versus local odontogenic bacterial infections: comparison of microbial isolates. Eur Surg Res. 2008;40(2):220-4. DOI: 10.1159/000110864 External link
107.
Kuriyama T, Nakagawa K, Karasawa T, Saiki Y, Yamamoto E, Nakamura S. Past administration of beta-lactam antibiotics and increase in the emergence of beta-lactamase-producing bacteria in patients with orofacial odontogenic infections. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000 Feb;89(2):186-92. DOI: 10.1067/moe.2000.102040 External link
108.
Kuriyama T, Karasawa T, Nakagawa K, Nakamura S, Yamamoto E. Antimicrobial susceptibility of major pathogens of orofacial odontogenic infections to 11 beta-lactam antibiotics. Oral Microbiol Immunol. 2002 Oct;17(5):285-9. DOI: 10.1034/j.1399-302X.2002.170504.x External link
109.
Sakamoto H, Aoki T, Kise Y, Watanabe D, Sasaki J. Descending necrotizing mediastinitis due to odontogenic infections. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000 Apr;89(4):412-9. DOI: 10.1016/S1079-2104(00)70121-1 External link
110.
Cachovan G, Böger RH, Giersdorf I, Hallier O, Streichert T, Haddad M, Platzer U, Schön G, Wegscheider K, Sobottka I. Comparative efficacy and safety of moxifloxacin and clindamycin in the treatment of odontogenic abscesses and inflammatory infiltrates: a phase II, double-blind, randomized trial. Antimicrob Agents Chemother. 2011 Mar;55(3):1142-7. DOI: 10.1128/AAC.01267-10 External link
111.
Pigrau C, Almirante B, Rodriguez D, Larrosa N, Bescos S, Raspall G, Pahissa A. Osteomyelitis of the jaw: resistance to clindamycin in patients with prior antibiotics exposure. Eur J Clin Microbiol Infect Dis. 2009 Apr;28(4):317-23. DOI: 10.1007/s10096-008-0626-z External link
112.
Sedghizadeh PP, Kumar SK, Gorur A, Schaudinn C, Shuler CF, Costerton JW. Microbial biofilms in osteomyelitis of the jaw and osteonecrosis of the jaw secondary to bisphosphonate therapy. J Am Dent Assoc. 2009 Oct;140(10):1259-65. DOI: 10.14219/jada.archive.2009.0049 External link
113.
Gaetti-Jardim Júnior E, Fardin AC, Gaetti-Jardim EC, de Castro AL, Schweitzer CM, Avila-Campos MJ. Microbiota associated with chronic osteomyelitis of the jaws. Braz J Microbiol. 2010 Oct;41(4):1056-64. DOI: 10.1590/S1517-838220100004000025 External link
114.
Ang JY, Asmar BI. Multidrug-resistant viridans streptococcus (MDRVS) osteomyelitis of the mandible successfully treated with moxifloxacin. South Med J. 2008 May;101(5):539-40. DOI: 10.1097/SMJ.0b013e3181684ee3 External link
115.
Tuzuner-Oncul AM, Ungor C, Dede U, Kisnisci RS. Methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis of the mandible. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009 Jun;107(6):e1-4. DOI: 10.1016/j.tripleo.2009.03.002 External link
116.
Baltensperger M, Grätz K, Bruder E, Lebeda R, Makek M, Eyrich G. Is primary chronic osteomyelitis a uniform disease? Proposal of a classification based on a retrospective analysis of patients treated in the past 30 years. J Craniomaxillofac Surg. 2004 Feb;32(1):43-50. DOI: 10.1016/j.jcms.2003.07.008 External link
117.
Deutsche Gesellschaft für Mund-, Kiefer- und Gesichtschirurgie (DGMKG). Bisphosphonat-assoziierte Kiefernekrose (BP-ONJ) und andere Medikamenten-assoziierte Kiefernekrosen. S3-Leitlinie. AWMF-Registernummer 007-091. AWMF; 2012.
118.
Wei X, Pushalkar S, Estilo C, Wong C, Farooki A, Fornier M, Bohle G, Huryn J, Li Y, Doty S, Saxena D. Molecular profiling of oral microbiota in jawbone samples of bisphosphonate-related osteonecrosis of the jaw. Oral Dis. 2012 Sep;18(6):602-12. DOI: 10.1111/j.1601-0825.2012.01916.x External link
119.
Nair M, Krishnan A. Antibiotic releasing biodegradable scaffolds for osteomyelitis. Curr Drug Deliv. 2014;11(6):687-700. DOI: 10.2174/1567201811666140414120002 External link
120.
Koorbusch GF, Fotos P, Goll KT. Retrospective assessment of osteomyelitis. Etiology, demographics, risk factors, and management in 35 cases. Oral Surg Oral Med Oral Pathol. 1992 Aug;74(2):149-54. DOI: 10.1016/0030-4220(92)90373-X External link
121.
Smego RA Jr, Foglia G. Actinomycosis. Clin Infect Dis. 1998 Jun;26(6):1255-61; quiz 1262-3. DOI: 10.1086/516337 External link
122.
Wong VK, Turmezei TD, Weston VC. Actinomycosis. BMJ. 2011 Oct;343:d6099.
123.
Martin MV. The use of oral amoxycillin for the treatment of actinomycosis. A clinical and in vitro study. Br Dent J. 1984 Apr;156(7):252-4. DOI: 10.1038/sj.bdj.4805331 External link
124.
Vogl TJ, Al-Nawas B, Beutner D, Geisthoff U, Gutinas-Lichius O, Naujoks C, Reich R, Schröder U, Sproll C, Teymoortash A, Ußmüller J, Wittekindt C, Zenk J, Fischer S. Updated S2K AWMF guideline for the diagnosis and follow-up of obstructive sialadenitis - relevance for radiologic imaging. Rofo. 2014 Sep;186(9):843-6. DOI: 10.1055/s-0034-1366867 External link
125.
Hagelskjaer Kristensen L, Prag J. Localised Fusobacterium necrophorum infections: a prospective laboratory-based Danish study. Eur J Clin Microbiol Infect Dis. 2008 Aug;27(8):733-9. DOI: 10.1007/s10096-008-0497-3 External link
126.
Rusan M, Klug TE, Ovesen T. An overview of the microbiology of acute ear, nose and throat infections requiring hospitalisation. Eur J Clin Microbiol Infect Dis. 2009 Mar;28(3):243-51. DOI: 10.1007/s10096-008-0619-y External link
127.
Lamey PJ, Boyle MA, MacFarlane TW, Samaranayake LP. Acute suppurative parotitis in outpatients: microbiologic and posttreatment sialographic findings. Oral Surg Oral Med Oral Pathol. 1987 Jan;63(1):37-41. DOI: 10.1016/0030-4220(87)90337-9 External link
128.
Brook I. The bacteriology of salivary gland infections. Oral Maxillofac Surg Clin North Am. 2009 Aug;21(3):269-74. DOI: 10.1016/j.coms.2009.05.001 External link
129.
Lewis MA, Lamey PJ, Gibson J. Quantitative bacteriology of a case of acute parotitis. Oral Surg Oral Med Oral Pathol. 1989 Nov;68(5):571-5. DOI: 10.1016/0030-4220(89)90242-9 External link
130.
Troeltzsch M, Pache C, Probst FA, Troeltzsch M, Ehrenfeld M, Otto S. Antibiotic concentrations in saliva: a systematic review of the literature, with clinical implications for the treatment of sialadenitis. J Oral Maxillofac Surg. 2014 Jan;72(1):67-75. DOI: 10.1016/j.joms.2013.06.214 External link