Study: Notable Antibiotic Resistance in Severe Orofacial Infections
Bacterial resistance to commonly used empiric therapy in head and neck infections is frequently reported. Conventional treatment for these types of infections usually has been high dose penicillins, or clindamycin in patients with penicillin allergy.
Severe orofacial bacterial infections can progress and lead to life-threatening complications including pneumonia, descending mediastinitis, thoracic empyema, pericarditis, septic shock, intraorbital infection, and intracranial spread. Bacterial resistance to antibiotics is a determining factor in progression to these complications.
A recent study assessed the antibiotic resistance profile in patients with severe orofacial infections treated at Massachusetts General Hospital in Boston from 2009 through 2014. Penicillin resistance was found in 32.5% of aerobic isolates, and clindamycin resistance was found in 29.3%. Streptococcus viridans and Staphylococcus species showed increased resistance to clindamycin and erythromycin compared with historic controls.
The authors of the study were from Harvard School of Dental Medicine and Massachusetts General Hospital. The study can be accessed at: Kim MK, Chuang SK, August M. “Antibiotic Resistance in Severe Orofacial Infections.” J Oral Maxillofac Surg 2017; 75: 962-968.
Bacterial Resistance to Penicillin
According to the authors, 13% of Streptococci viridans cases show resistance to penicillin. This is of some concern, since Streptococci viridans is the most common isolate in head and neck infections. Staphylococcus species are also associated with significant penicillin resistance. Prevotella species have been shown to be increasingly resistant to penicillins based on the bacterial production of beta-lactamase enzymes
Bacterial Resistance to Clindamycin
The authors state that Streptococcus milleri resistance to clindamycin has been reported, and clindamycin has minimal efficacy if aerobic gram-negative bacterial are the causative pathogens. They reference studies which report 18% clindamycin resistance in aerobic bacteria and 11% resistance in anaerobic isolates in deep space orofacial infections.
Based on these current patterns of resistance to the commonly used antibiotics in orofacial infections, the purpose of this retrospective study was to answer three clinical questions:
- Has the pattern of antibiotic resistance in orofacial infections changed ominously during the past decade?
- How often has empiric therapy needed to be altered based on lack of clinical improvement and antibiotic resistance data?
- Has the presence of resistant bacteria led to prolongation of the hospital stay in these patients?
This was a five-year retrospective study which identified all patients admitted to Massachusetts General Hospital for the treatment of orofacial infection from 2009 through 2014. Inclusion criteria were:
- Hospital admission
- Need for a surgical procedure
- Availability of complete medical records
- Microbiology data, including aerobic and anaerobic cultures and aerobic sensitivity data
Comparison with a similar cohort of patients treated at a tertiary care facility for orofacial infection from 1997 through 2003 was used as the historic control, allowing for comparison of changes in antibiotic bacterial sensitivities and antibiotic resistance.
To determine whether emerging patterns of antibiotic resistance changed since the previous decade, microbiologic culture susceptibility data were compared with those from the historical cohort. In addition, potential correlation between antibiotic resistance and length of hospital stay was evaluated. Linear regression, logistic analyses, and Fisher exact testing was used to analyze the data.
Inclusion criteria identified 60 cases of orofacial infection. With a mean age of 45 years, ranging from 16 to 92 years, the cases included 36 men and 24 women. The average number of days in the hospital was 5.48, ranging from 1 to 43 days.
Sixty-eight percent of patients were taking oral antibiotics at the time of hospital admission.
Physical examination documented the following symptoms:
- Trismus: 75.5% of cases
- Swelling: 70%
- Fluctuance: 47%
- Symphadenopathy: 36%
- Uvula: 9%
- Airway compromise: 9%
- All 60 cases had at least 1 aerobic isolate with an average of 1.97 isolates documented per patient
- 91 aerobic species were identified, with 49 isolates being of the Streptococcus species:
- S viridans: 46 of 91, or 51%
- Beta-hemolytic Streptococcus: 3 of 91, or 3%
- 30 of the 91 isolates (33%) were coagulase-negative Staphylococcus species
- 43 patients (72%) had positive anaerobic cultures, with 49 isolates identified
- The most common designation of isolates was “rare anaerobes not classified” (30 of 49, or 61.2%)
- Propionobacterium species were present in 6 isolates (12.2%)
- Gram-negative rods were present in 5 isolates (10.2%)
- Peptostreptococcus species were present in 4 isolates (8.2%)
- “Other” organisms were reported in 4 isolate (8.2%)
- Only the aerobic species underwent routine sensitivity testing
- Penicillin resistance was found in 32.5% of aerobic isolates. This was seen in Staphylococcus species (73%), but seldom in Streptococcus species (2%)
- Clindamycin resistance was found in 29.3% of aerobic isolates. This was seen in S viridans (including S milleri and Streptococcus anginosus groups; 31.8%), and coagulase-negative Staphylococcus species (10.5%)
- Erythromycin resistance was found in 30% of aerobic isolates
- Penicillin: 12.9% resistant historical; 2% resistant current
- Clindamycin: 13.7% resistant historical; 32% resistant current
- Erythromycin: 16.6% resistant historical; 29% resistant current
- Vancomycin: 0 resistant historical; 0 resistant current
- Penicillin: 72.7% resistant historical; 73% resistant current
- Clindamycin: 10.5% resistant historical; 23% resistant current
- Erythromycin: 25% resistant historical; 30% resistant current
- Vancomycin: 0 resistant historical; 0 resistant current
- Ampicillin and sulbactam (58% of cases)
- Clindamycin (22% of cases)
- Penicillin (8% of cases)
Multiple-space fascial involvement was reported in approximately 80% of the cases, with the most commonly reported anatomic space being the submandibular in single and multiple space infections.
Microbiology results for aerobic isolates:
Microbiology results for anaerobic isolates:
Aerobic bacteria antibiotic resistance:
Comparison to historic controls
The 1997-2003 reference study reported susceptibility data for S viridans and the Staphylococcus species only. The authors compared those data to the current 2009-2014 data.
Empiric antibiotics given in the hospitalized patients were:
The empiric antibiotic was changed in 14 out of 60 cases (24%). Of those 14, four were changed after infectious disease consultation and three were changed because of the presence of resistant species in the culture. No information was provided as to the reasons the empiric antibiotic was changed in the other seven cases.
A statistically meaningful correlation with antibiotic resistance was seen for younger patient age, positive history of surgery, and number of aerobic organisms isolated.
No statistical prolongation in hospitalization was found for antibiotic resistance.
There was no statistical change in antibiotic regimen for cases in which resistant organisms were identified.
The need for changes in antibiotics, repeat surgical drainage, and increased serum urea nitrogen levels correlated with longer hospital stay.
According to the authors, the three clinical questions were answered from the study data as follows:
1. Has the pattern of antibiotic resistance in orofacial infections changed ominously during the past decade?
A serious increase in clindamycin and erythromycin resistance was found for S viridans and Staphylococcus species.
2. How often has empiric therapy needed to be altered based on lack of clinical improvement and antibiotic resistance data?
Empiric antibiotic therapy was changed in 14 out of 60 cases. Conclusion was no statistical change occurred in empirical antibiotic regimens.
3. Has the presence of resistant bacteria led to prolongation of the hospital stay in these patients?
The presence of antibiotic resistance failed to show statistically relevant correlations to prolongation of hospital stay.
The clindamycin issue
The authors expressed interest in the apparent increased bacterial resistance to clindamycin. This antibiotic is often used as monotherapy and is commonly used as an optional agent in penicillin-allergic patients.
Apparently, the mechanism for the bacterial development of resistance to clindamycin involves modification of the binding site on the ribosome of the bacteria through methylation. This mechanism may also explain concomitant resistance to the macrolides which include erythromycin, clarithromycin, and azithromycin. Therefore, as seen in this present study, a common pattern of clindamycin and erythromycin resistance often occurs.
Clindamycin resistance is to be considered as a potential threat for failed therapy in the treatment of deep space head and neck infections when S milleri group is identified. The authors indicated that Streptococcus milleri is a notorious abscess former, and a careful choice of antibiotics is necessary when culture data disclose the presence of this bacterium.
The authors concluded the paper by expressing the need for prospective studies with more complete identification of aerobic and anaerobic bacteria, with sensitivity testing performed on the predominant species identified. Further, they commented that “conducting antibiotic resistance studies on all isolated species, including oropharyngeal flora and anaerobes, would provide a more complete picture in describing the pattern of antibiotic resistance.”
Richard L. Wynn, BS Pharm, PhD, is professor of pharmacology at the Baltimore College of Dental Surgery, Dental School, University of Maryland Baltimore.
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