Show Summary Details
Page of

Oral bacterial infections 

Oral bacterial infections
Chapter:
Oral bacterial infections
Author(s):

Anthony Chow

DOI:
10.1093/med/9780199543588.003.0019
Page of

PRINTED FROM OXFORD MEDICINE ONLINE (www.oxfordmedicine.com). © Oxford University Press, 2020. All Rights Reserved. Under the terms of the licence agreement, an individual user may print out a PDF of a single chapter of a title in Oxford Medicine Online for personal use (for details see Privacy Policy and Legal Notice).

Subscriber: null; date: 10 July 2020

Introduction

Bacterial infections of the oral cavity most commonly arise from the indigenous microflora that colonize unique niches in the mouth such as the teeth, gingival sulcus, tongue, buccal mucosa, or the saliva. Under normal conditions, they exist as commensal flora in a symbiotic relationship with the host, serving the important function of preventing colonization and invasion by exogenous pathogens. However, under certain pathological conditions such as poor oral hygiene, systemic disease, immunodeficiency, or mucosal injury from irradiation or chemotherapy, these micro-organisms can undergo adaptations that predispose to pathogenicity [1].

It is important to recognize that these endogenous infections do not fit the pattern of classical infectious diseases caused by exogenous pathogens. Hence, these endogenous infections are often caused by a microflora that is often polymicrobial (rather than monomicrobial), and involve both aerobic and anaerobic bacteria. Furthermore, there is an orderly bacterial succession from initiation events to established disease, such that the flora of the advanced lesion may bear little resemblance to the flora of the incipient lesion[2]. Additionally, in a polymicrobial infection, it is often difficult to determine which constituents are the initiators of infection, which are the perpetuators of infection, and which are simply innocent bystanders.

The oral bacterial microflora is discussed in detail in Chapter 17.

Aetiology

Several risk factors for oral infections have been identified in the cancer patient, including poor oral/dental health, oral mucositis, myelosuppression, and salivary gland dysfunction. These risk factors represent impairment of the oral host-defence mechanisms. The oral host-defence mechanisms are discussed in detail in Chapter 17.

Clinical features

Bacterial infections are a major cause of morbidity and mortality in cancer patients receiving local irradiation, systemic chemotherapy, or haematopoietic stem cell transplantation[3,4]. A variety of endogenous bacterial infections are encountered, including exacerbations of dental caries or periodontal disease, necrotizing gingivitis or stomatitis, odontogenic deep space infections, and bacterial overgrowth and secondary infections complicating oral mucositis. Furthermore, the oral cavity is an important source of bacteraemia and sepsis, particularly in patients with neutropaenia[5]. It should be noted that, in the immunocompromised patient, the classical manifestations of an inflammatory response to an infection are frequently muted (and so the presence of infection may be missed).

Odontogenic infections

Dental caries

There is growing awareness of the infectious nature of dental caries, and that only certain micro-organisms residing within dental plaques are cariogenic (the ‘specific’ plaque hypothesis)[2]. Dental caries are primarily caused by micro-organisms within the supragingival plaque, which is composed mainly of facultative anaerobic and microaerophilic Gram-positive cocci and rods. The mutans streptococci group, notably Streptococcus mutans and S. sobrinus, are the primary organisms associated with dental caries[6]. Root caries are also associated with Actinomyces species, including A. naeslundii and A. viscosus. Plaque-bacteria ferment sugar, leading to acid production which penetrates the tooth surface and causes demineralization.

The earliest clinical finding is the presence of pits and fissures on the affected tooth surface, which gradually become stained because of demineralization of the enamel and dentine (Figure 19.1). The lesions have a soft-to-rubbery texture. Progressive demineralization leads to collapse and cavitation, until the enamel surface is destroyed and the dental pulp becomes exposed (Figure 19.2). Clinically, root caries are more difficult to diagnose than coronal caries, since they tend to occur on the interproximal tooth surfaces where gingival recession has occurred. They are also more common, because of retained food debris and relative inaccessibility to brushing. Coronal caries are more likely to present as recurrent lesions around existing restorations.


              Fig. 19.1 Early dental caries.

Fig. 19.1
Early dental caries.

Source: Reproduced with permission from Davies A and Finlay I (2005), Oral Care in Advanced Disease. Oxford University Press, Oxford


              Fig. 19.2 Advanced dental caries.

Fig. 19.2
Advanced dental caries.

Source: Reproduced with permission from Davies A and Finlay I (2005), Oral Care in Advanced Disease. Oxford University Press, Oxford

Pulpal infection

Pulp tissue that is exposed to oral bacteria invariably becomes infected. Pulpal infections are usually caused by a polymicrobial flora of obligate anaerobes, primarily Bacteroides species, Porphyromonas endodontalis, Eubacterium species, Fusobacterium nucleatum, and Peptostreptococcus micros[1]. The pressure builds rapidly within the pulp chamber once inflammation is established. This usually elicits excruciating pain along branches of cranial nerve V; the pain may worsen in response to heat or cold in the oral environment. Eventually, ischaemia and necrosis of the pulp tissue develops due to occlusion of blood vessels entering at the apical foramen. When this occurs, the sensory nerve endings are no longer viable, and so dental pain ceases to be a problem. Infection may extend through the necrotic apical root canal causing a localized periodontitis or dentoalveolar abscess. Chronic infection leads to osteitis and occasionally osteomyelitis of the jaws.

Pericoronitis

Pericoronitis is an acute localized infection caused by the entrapment of food particles and micro-organisms under the gum flaps of a partially erupted or an impacted molar tooth. The mandibular molars are most commonly involved. Prominent symptoms include pain, limitation of mouth opening (trismus), discomfort on mastication and swallowing, and facial swelling. Clinically, the pericoronal tissues are swollen and erythematous, and digital pressure can often express an exudate from under the infected flap. The breath is usually malodorous, and painful lymphadenopathy may be noted in the submandibular region.

Persistent periapical dental infection may lead to chronic osteomyelitis of the jaws [7]. Similarly, periapical infections arising from anterior maxillary teeth may perforate the Schneidarian membrane to cause chronic or recurrent maxillary sinusitis.

Periodontal disease

Periodontal disease affects the connective tissues supporting the tooth, including the gingiva, periodontal ligament, and alveolar bone. The process can be confined to the soft tissues supporting the tooth causing gingivitis, or involve deeper structures with loss of alveolar support for the tooth, eventually leading to tooth loss. Periodontal disease is mainly caused by micro-organisms within the subgingival dental plaque, which penetrate the gingival epithelium and elicit an inflammatory response[8]. The microflora is predominated by Actinomyces species such as A. viscosus and A. naeslundii, and Porphyromonas gingivalis. Other organisms such as S. sanguis and S. anginosus are also found. As periodontal disease advances, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia, and Treponema denticola become predominant[2]. In addition to plaque-induced inflammation, other conditions that can trigger gingival inflammation include hormonal changes (e.g. pregnancy), and medications (e.g. ciclosporin, phenytoin). Periodontal infection is a major source for fever and sepsis in cancer patients, and causes considerable morbidity especially in patients with neutropaenia.[3] However, gingival infection can be missed, because signs of gingival inflammation such as redness and swelling may be muted as a result of neutropaenia. Radiological investigation (e.g. bite-wing X-ray, orthopantogram) is an essential aspect of making the diagnosis (Figure 19.3).


              Fig. 19.3 Simple gingivitis.

Fig. 19.3
Simple gingivitis.

Source: Reproduced with permission from Davies A and Finlay I (2005), Oral Care in Advanced Disease. Oxford University Press, Oxford

Necrotizing gingivitis/stomatitis

Necrotizing gingivitis

Necrotizing gingivitis (also known as acute necrotizing ulcerative gingivitis, ‘trench mouth’, and Vincent's angina) is an aggressive form of periodontitis associated with rapid progression and tissue destruction. The gingival connective tissues are invaded by a polymicrobial microflora dominated by Treponema denticola, Prevotella intermedia, and Fusobacterium nucleatum[9]. Herpesviruses (i.e. herpes simplex virus-1 (HSV-1), Epstein–Barr virus (EBV), and cytomegalovirus (CMV)) are frequently found to coexist with periodontopathic bacteria, and so have been suggested to play a role in the pathogenesis of necrotizing gingivitis[10]. However, a causal relationship remains to be determined. Necrotizing gingivitis is associated with severe impairment of immune responses due to underlying disease, and may be one of the first signs of acute leukaemia or the acquired immune deficiency syndrome (AIDS)[11]. It may also occur in patients undergoing haematopoietic stem cell transplantation. Necrotizing gingivitis is characterized by ulceration, bleeding, and necrosis of the interdental soft tissues (Figure 19.4). The onset is abrupt, and the patient usually complains of pain and systemic manifestations of infection.


              Fig. 19.4 Necrotizing gingivitis.

Fig. 19.4
Necrotizing gingivitis.

Source: Reproduced with permission from Davies A and Finlay I (2005), Oral Care in Advanced Disease. Oxford University Press, Oxford

Necrotizing stomatitis

Necrotizing stomatitis (also known as gangrenous stomatitis, noma, and cancrum oris) bears some resemblance to necrotizing gingivitis, but is more focal and destructive, involving deeper tissues to the gingiva. Cultures and molecular analysis from advancing lesions reveal a diverse microflora dominated by fusospirochaetal organisms such as Treponema vincentii, Fusobacterium nucleatum, and Prevotella melaninogenica[12]. It has been described following irradiation of the head and neck (in the absence of significant periodontal disease)[13]. The earliest lesion is a small, painful red spot or vesicle on the attached gingiva in the premolar or molar region of the mandible. A necrotic ulcer rapidly develops and undermines the deeper tissue. Painful cellulitis of the cheeks and lips is observed as the lesion extends outwards in a cone-like fashion. Within a short period, sloughing of necrotic soft tissues occurs, exposing the underlying deep tissues (e.g. bone).

Bacterial sialoadenitis

Sialoadenitis, or infection of salivary tissue, most commonly involves the parotid gland. However, the submandibular and sublingual glands can also be affected. Common pathogens include Staphylococcus aureus, Enterobacteriaceae, and anaerobic Gram-negative rods such as Prevotella and Fusobacterium species[14]. Risk factors for infection include myelosuppression and ductal obstruction caused by calculi, irradiation, and salivary gland hypofunction. Clinically, the patient presents with a sudden onset of pain and swelling over the affected gland. Thus, parotitis is characterized by swelling of the pre- and post-auricular areas, which may extend towards the angle of the mandible. In addition, suppuration may be noted at the orifice of the Stenson's duct. Systemic features of infection are generally present (e.g. fever, chills). Progression of the infection may lead to massive swelling of the neck (resulting in respiratory obstruction), osteomyelitis of adjacent facial bones, and septicaemia.

Odontogenic deep-space infections

Odontogenic deep-space infections tend to involve the more superficial masticator, buccal, canine, submental, and infratemporal spaces. Extension may occur to involve the deeper fascial spaces of the head and neck, such as the submandibular, sublingual, lateral pharyngeal, and retropharyngeal spaces[15]. The third mandibular molars are the most common sources for odontogenic deep-space infections[16]. Infections involving the mandibular molars may extend into the submandibular and sublingual spaces resulting in massive swelling of the base of the tongue and acute airway obstruction (Ludwig's angina), while those involving maxillary premolars may extend infratemporally into the orbit. Similarly, infections arising from the masticator spaces may extend into the lateral pharyngeal space and eventually invade the carotid sheath and the internal jugular vein (Lemierre syndrome). Finally, infection involving the retropharyngeal space may dissect directly into the posterior mediastinum resulting in an acute necrotizing mediastinitis. The clinical features of these deep-space infections are summarized in Table 19.1[17].

Table 19.1 Clinical features of odontogenic deep space infections [17]

Deep space infection

Usual site of origin

Clinical features

Pain

Trismus

Swelling

Dysphagia

Dyspnoea

Masticator

  • Masseteric & Pterygoid

  • Temporal

Molars (especially 3rd)

Posterior maxillary molars

Present

Present

Prominent

None

May not be evident (deep)

Face, orbit (late)

Absent

Absent

Absent

Absent

Buccal

Biscuspids, molars

Minimal

Minimal

Cheek (marked)

Absent

Absent

Canine

Maxillary canines, incisors

Moderate

None

Upper lip, canine fossa

Absent

Absent

Infratemporal

Posterior maxillary molars

Present

None

Face, orbit (late)

Occasional

Occasional

Submental

Mandibular incisors

Moderate

None

Chin (firm)

Absent

Absent

Parotid

Masseteric spaces

Intense

None

Angle of jaw (marked)

Absent

Absent

Submandibular

Mandibular molars (2nd, 3rd)

Present

Minimal

Submandibular

Absent

Absent

Sublingual

Mandibular incisors

Present

Minimal

Floor of mouth (tender)

Present if bilateral

Present if bilateral

Lateral pharyngeal

  • Anterior

  • Posterior

Masticator spaces

Masticator spaces

Intense

Minimal

Prominent

Minimal

Angle of jaw

Posterior pharynx

Present

Present

Occasional

Severe

Retropharyngeal

Lateral pharyngeal space

Present

Minimal

Posterior pharynx (midline)

Present

Present

Oral mucositis

Although oral mucositis is not generally considered an infectious disease, there is considerable support for secondary bacterial overgrowth, and invasion of the submucosa during the so-called ulcerative phase[18]. Patients with ulceration associated with mucositis have a significantly increased risk of bacteraemia and septicaemia compared to patients without ulceration[19,20]. Oral mucositis is discussed in detail in Chapter 15.

Bacteraemia and sepsis

Bacteraemia and sepsis is a serious complication in patients with neutropaenia, particularly among those with a haematological malignancy. Bacteraemia in these patients are predominantly (∼70% cases) caused by Gram-positive cocci, particularly viridans streptococci and staphylococci[7,21]. Molecular analysis has revealed that bacteraemia with viridans stretpotocci is most likely derived from the oral cavity[22], whereas bacteraemia with coagulase-negative staphylococci most likely arises from the nasopharynx or the skin (i.e. intravenous catheters)[23]. Indeed, oropharyngeal colonization with viridans streptococci of a given ribotype has been shown to precede bacteraemia with the same ribotype[24]. Patients with viridans streptococcal bacteraemia are more likely to have poor dental health or oral mucositis than patients without streptococcal bacteraemia[20]. Bacteraemia associated with viridans streptococci is especially common in children, and causes considerable morbidity and mortality[22]. Thus, almost one-third of infected patients develop a shock syndrome[25].

Investigation

Microbiological investigation

A major challenge in the microbiological investigation of oral infections is how to distinguish true pathogens from commensal flora. The mere presence of an organism is insufficient to ascribe a causal role in a polymicrobial endogenous infection. This underscores the importance of proper specimen collection, and the need to correlate clinical information with laboratory data. Imaging techniques may also be useful in certain circumstances.

Aerobic and anaerobic blood cultures should always be obtained. Surface cultures obtained from mucosal sites are regularly contaminated by resident commensal flora and are generally not recommended. Direct microscopic examination of stained smears often provides more useful information. For closed-space infections, needle aspiration of pus is desirable, but is often not feasible due to neutropaenia and/or thrombocytopaenia. Specimens should be collected in appropriate transport medium and delivered as soon as possible to the laboratory under anaerobic conditions.

Occasionally, biopsy of specific lesions may be required in order to arrive at a histopathological diagnosis. Immunofluorescence staining and DNA probes or polymerase chain reaction (PCR) are increasingly available for pathogens that are fastidious or non-cultivable[26,27]. The benzoyl-DL-arginine-naphthylamide (BANA) test detects a trypsin-like enzyme produced by periodontopathic bacteria including Porphomonas gingivalis, Treponema denticola, and Tannerella forsythia. A positive BANA test correlates both qualitatively and quantitatively with the presence of these micro-organisms and is useful for the diagnosis of anaerobic periodontal infections[28].

Management

The management of odontogenic and other oromucosal infections in the cancer patient requires a multidisciplinary approach. A proactive approach is necessary for all patients, involving routine oral hygiene measures, and regular dental check ups/care. Chapter 5 discusses pretreatment screening/treatment in detail, whilst Chapter 6 discusses routine oral hygiene in detail.

Endogenous oral pathogens are no longer universally susceptible to penicillin. Thus, β‎-lactamase-producing anaerobic Gram-negative bacteria have been increasingly recognized[29]. They include Prevotella species, Porphyromonas species, Fusobacterium species, and others[30,31]. Indeed, failure of penicillin therapy in odontogenic infections due to these micro-organisms is well documented[32]. Thus, a β‎-lactam/β‎-lactamase-inhibitor combination should be considered if the clinical response to penicillin is suboptimal (and there is no evidence for loculated infection requiring surgical drainage). There are also increasing reports of in vitro resistance to metronidazole and azithromycin amongst Fusobacterium species and other anaerobic Gram-negative bacteria isolated from odontogenic infections[33]. However, the clinical significance of these findings is unclear at this time. Nevertheless, the emergence of resistance among oral bacteria is disconcerting, and is probably due to selection pressure from widespread and inappropriate use of broad-spectrum antibiotics.

The recommended antimicrobial regimens for various odontogenic and oromucosal infections in normal and immunocompromised hosts are summarized in Table 19.2. The selection of antimicrobial agents should be guided by their predicted antibacterial spectrum, and the bioavailability of oral or parenteral formulations. Since immunocompromised patients are particularly at risk for rapidly spreading orofacial infections, empirical broad-spectrum antimicrobial therapy is usually warranted. The antibiotic regimen must be broad-spectrum, bactericidal, and appropriate in dose and schedule. In hospitalized patients, and those with severe neutropaenia, it is prudent to cover for facultative Gram-negative bacilli as well as strepotococci and oral anaerobes. In addition, coverage for methicillin-resistant S. aureus (MRSA) may be required.

Table 19.2 Antimicrobial regimens for odontogenic and oromucosal infections

Clinical entity

Unique microbial species

Antimicrobial regimen

Supragingival dental plaque and dental caries

Streptococcus mutans

Other streptococci

Actinomyces spp.

Fluoride-containing dentifrices or oral rinses (e.g. sodium fluoride 1.1% or stannous fluoride 0.4%) used 2 or 3 times daily.

Fluoride-containing varnishes (e.g. sodium fluoride 5%) applied 3 or 4 times yearly

Chlorhexidine 0.12% oral rinses

Subgingival dental plaque and simple gingivitis

Streptococci,

Actinomyces spp

Spirochaetes

Penicillin G 1-4 MU IV q4-6h (or penicillin V 500 mg PO q8h) plus metronidazole 500 mg PO or IV q8h

Ampicillin-sulbactam 1.5-3 g IV q6h (or amoxicilin-clavulanate 500 mg PO q8h)

Clindamycin 450 mg PO or 600 mg IV q6-8 h

Periodontitis, early-onset, ‘aggressive’ or ‘localized juvenile’

Actinobacillus actinomycetemcomitans Porphyromonas gingivalis

Treponema denticoli

Prevotella intermedia

Tetracycline 500 mg PO q6h or 1 g IV q12h

Doxycycline 200 mg PO or IV q12h

Metronidazole 500 mg PO or IV q8h

Periodontitis, adult or ‘established’

Treponema denticoli

Other oral spirochaetes

Porphyromonas gingivalis

Prevotella intermedia

Tannerella forsythia

Topical minocycline microspheres

Topical doxycycline hyclate periodontal extended-release liquid

Necrotizing gingivitis/stomatitis

Prevotella intermedia Fusobacterium spp

Tannerella forsythia

Treponema denticoli

Other oral spirochaetes

Ampicillin-sulbactam 1.5-3 g IV q6h (or amoxicillin-clavulanate 500 mg PO q8h)

Metronidazole 500 mg PO or IV q8h

Clindamycin 450 mg PO or 600 mg IV q6-8h

Bacterial sialoadenitis

Staphylococcus aureus

Mixed anaerobes

Cloxacillin 2 g IV q4 h (or nafcillin 2 g IV q4h) plus either

metronidazole 500 mg IV or PO q6h, or clinamycin 600 mg IV or PO q6-8h

(For methicillin-resistance S. aureus, substitute cloxacillin or nafcillin with vancomycin 15-20 mg/kg IV to maintain trough serum concentrations ∼10-15 µg/mL or linezolid 600 mg IV or PO q12h or daptomycin 4-6 mg/kg IV q24 h)

Odontogenic deep space infections

Streptococcus viridans

Other streptococci

Peptostreptococcus spp Bacteroides spp

Other oral anaerobes

Normal hosts

Penicillin G 2-4 MU IV q4-6h, plus metronidazole 0.5 g IV q6h

Ampicillin-sulbactam 2 g IV q4h

Clindamycin 600 mg IV q6h

Doxycycline 200 mg IV q12h

Cefoxitin 1-2 g IV q6h

Moxifloxacin 400 mg IV q24h

Immunocompromised hosts

Cefotaxime 2 g IV q6h

Ceftizoxime 4 g IV q8h

Ticarcillin-clavulanate 3 g IV q4h

Piperacillin-tazobactam 3 g IV q4h

Imipenem 500 mg IV q6h

Meropenem 1 g IV q8h

References

1 Ruby J, Barbeau J (2002). The buccale puzzle: the symbiotic nature of endogenous infections of the oral cavity. Can J Infect Dis, 13(1), 34–41.Find this resource:

2 Loesche W (2007). Dental caries and periodontitis: contrasting two infections that have medical implications. Infect Dis Clin North Am, 21(2), 471–502, vii.Find this resource:

3 Raber-Durlacher JE, Epstein JB, Raber J, et al. (2002). Periodontal infection in cancer patients treated with high-dose chemotherapy. Support Care Cancer, 10(6), 466–73.Find this resource:

4 Heimdahl A (1999). Prevention and management of oral infections in cancer patients. Support Care Cancer, 7(4), 224–8.Find this resource:

5 Lockhart PB, Loven B, Brennan MT, Fox PC (2007). The evidence base for the efficacy of antibiotic prophylaxis in dental practice. J Am Dent Assoc, 138(4), 458–74.Find this resource:

6 Marsh PD (1999). Microbiologic aspects of dental plaque and dental caries. Dent Clin North Am, 43(4), 599–614, v–vi.Find this resource:

7 Lerman MA, Laudenbach J, Marty FM, Baden LR, Treister NS (2008). Management of oral infections in cancer patients. Dent Clin North Am, 52(1), 129–53, ix.Find this resource:

8 Van Dyke TE, Serhan CN (2003). Resolution of inflammation: a new paradigm for the pathogenesis of periodontal diseases. J Dent Res, 82(2), 82–90.Find this resource:

9 Bermejo-Fenoll A, Sanchez-Perez A (2004). Necrotising periodontal diseases. Med Oral Patol Oral Cir Bucal, 9(Suppl), 114–19.Find this resource:

10 Slots J (2007). Herpesviral-bacterial synergy in the pathogenesis of human periodontitis. Curr Opin Infect Dis, 20(3), 278–83.Find this resource:

11 Robinson PG (2002). The significance and management of periodontal lesions in HIV infection. Oral Dis, 8(Suppl 2), 91–7.Find this resource:

12 Paster BJ, Falkler JW Jr, Enwonwu CO, et al. (2002). Prevalent bacterial species and novel phylotypes in advanced noma lesions. J Clin Microbiol, 40(6), 2187–91.Find this resource:

13 Mayorca A, Hazime N, Dekeister C, Paoli JR (2002). Necrotizing stomatitis after radiotherapy in a patient with AIDS: case report. J Oral Maxillofac Surg, 60(1), 100–1.Find this resource:

14 Brook I (2003). Acute bacterial suppurative parotitis: microbiology and management. J Craniofac Surg, 14(1), 37–40.Find this resource:

15 Reynolds SC, Chow AW (2007). Life-threatening infections of the peripharyngeal and deep fascial spaces of the head and neck. Infect Dis Clin North Am, 21(2), 557–76, viii.Find this resource:

16 Chow AW (1992). Life-threatening infections of the head and neck. Clin Infect Dis, 14(5), 991–1002.Find this resource:

17 Hull MW, Chow AW (2005). An approach to oral infections and their management. Curr Infect Dis Rep, 7(1), 17–27.Find this resource:

18 Treister N, Sonis S (2007). Mucositis: biology and management. Curr Opin Otolaryngol Head Neck Surg, 15(2), 123–9.Find this resource:

19 Rondinelli PI, Ribeiro KC, de Camargo B (2006). A proposed score for predicting severe infection complications in children with chemotherapy-induced febrile neutropenia. J Pediatr Hematol Oncol, 28(10), 665–70.Find this resource:

20 Bochud PY, Eggiman P, Calandra T, Van Melle G, Saghafi L, Francioli P (1994). Bacteremia due to viridans streptococcus in neutropenic patients with cancer: clinical spectrum and risk factors. Clin Infect Dis, 18(1), 25–31.Find this resource:

21 Kurt B, Flynn P, Shenep JL, et al. (2008). Prophylactic antibiotics reduce morbidity due to septicemia during intensive treatment for pediatric acute myeloid leukemia. Cancer, 113(2), 376–82.Find this resource:

22 Reilly AF, Lange BJ (2007). Infections with viridans group streptococci in children with cancer. Pediatr Blood Cancer, 49(6), 774–80.Find this resource:

23 Costa SF, Barone AA, Miceli MH, et al. (2006). Colonization and molecular epidemiology of coagulase-negative Staphylococcal bacteremia in cancer patients: a pilot study. Am J Infect Control, 34(1), 36–40.Find this resource:

24 Wisplinghoff H, Reinert RR, Cornely O, Seifert H (1999). Molecular relationships and antimicrobial susceptibilities of viridans group streptococci isolated from blood of neutropenic cancer patients. J Clin Microbiol, 37(6), 1876–80.Find this resource:

25 Gamis AS, Howells WB, DeSwarte-Wallace J, Feusner JH, Buckley JD, Woods WG (2000). Alpha hemolytic streptococcal infection during intensive treatment for acute myeloid leukemia: a report from the Children's cancer group study CCG-2891. J Clin Oncol, 18(9), 1845–55.Find this resource:

26 Roscoe DL, Hoang L (2007). Microbiologic investigations for head and neck infections. Infect Dis Clin North Am, 21(2), 283–304, v.Find this resource:

27 Slots J, Ashimoto A, Flynn MJ, Li G, Chen C (1995). Detection of putative periodontal pathogens in subgingival specimens by 16S ribosomal DNA amplification with the polymerase chain reaction. Clin Infect Dis, 20(Suppl 2), S304-7: S304–7.Find this resource:

28 Loesche WJ, Bretz WA, Kerschensteiner D, et al. (1990). Development of a diagnostic test for anaerobic periodontal infections based on plaque hydrolysis of benzoyl-DL-arginine-naphthylamide. J Clin Microbiol, 28(7), 1551–9.Find this resource:

29 Brook I (1988). Beta-lactamase producing bacteria in head and neck infection. Laryngoscope, 98(4), 428–31.Find this resource:

30 Brook I (1993). Infections caused by beta-lactamase-producing Fusobacterium spp. in children. Pediatr Infect Dis, 12(6), 532–3.Find this resource:

31 Brook I (2002). Antibiotic resistance of oral anaerobic bacteria and their effect on the management of upper respiratory tract and head and neck infections. Semin Respir Infect, 17(3), 195–203.Find this resource:

32 Heimdahl A, von Konow L, Nord CE (1980). Isolation of beta-lactamase producing Bacteroides strains associated with clinical failures with penicillin treatment of human orofacial infections. Arch Oral Biol, 25(10), 689–92.Find this resource:

33 Bresco-Salinas M, Costa-Riu N, Berini-Aytes L, Gay-Escoda C (2006). Antibiotic susceptibility of the bacteria causing odontogenic infections. Med Oral Patol Oral Cir Bucal, 11(1), E70–5.Find this resource: