Anti-anaerobic antibacterials may increase risk of adverse clinical outcomes in critically ill patients

 

Critically ill patients routinely receive antibiotics with activity against anaerobic gut bacteria. Yet in other disease states and animal models, gut anaerobes are protective against pneumonia, organ failure, and mortality.

Rishi Chanderraj et al. from the University of Michigan Medical School, Ann Arbor, MI; designed a translational series of analyses and experiments to determine the effects of anti-anaerobic antibiotics on the risk of adverse clinical outcomes among critically ill patients. Their finding were published in the Eur Respir J in October 2022. 

The authors conducted a retrospective single-center cohort study of 3032 critically ill patients, comparing patients who did and did not receive early anti-anaerobic antibiotics. The investigators retrospectively compared ICU outcomes (ventilator-associated pneumonia-free survival, infection-free survival, overall survival) in all patients, and changes in gut microbiota in a 116-patient subcohort. They also studied in murine models, the effects of anaerobe depletion in infectious (K. pneumoniae and S. aureus pneumonia) and noninfectious (hyperoxia) injury models.

The investigators found that early administration of anti-anaerobic antibiotics was associated with decreased VAP-free survival, infection-free survival, and overall survival. Patients who received anti-anaerobic antibiotics had decreased initial gut bacterial density (p=0.00038), increased microbiome expansion during hospitalization (p=0.011), and domination by Enterobacteriaceae spp. (p=0.045). Enterobacteriaceae were also enriched among respiratory pathogens in anti-anaerobic treated patients. In murine models, treatment with anti-anaerobic antibiotics increased susceptibility to Enterobacteriaceae pneumonia (p<0.05) and increased the lethality of hyperoxia (p=0.0002).

The investigators concluded that in critically ill patients, early treatment with anti-anaerobic antibiotics is associated with increased mortality. Mechanisms may include enrichment of the gut with respiratory pathogens, but increased mortality is incompletely explained by infections alone. Given consistent clinical and experimental evidence of harm, the widespread use of anti-anaerobic antibiotics should be reconsidered. Since the current study was retrospective, prospective studies are warranted to further evaluate this issue.

Oral Microbiome and SARS-CoV-2: Beware of Lung Co-infection

 

Bao et al. Sichuan University, Chengdu, China; presented a  review on the role of the oral microbiome in the current global pandemic.

The new coronavirus SARS-CoV-2, the cause of COVID-19, has become a public health emergency of global concern. Like the SARS and influenza pandemics, there have been a large number of cases coinfected with other viruses, fungi, and bacteria, some of which originate from the oral cavity. Capnocytophaga, Veillonella, and other oral opportunistic pathogens were found in the BALF of the COVID-19 patients by mNGS. Risk factors such as poor oral hygiene, cough, increased inhalation under normal or abnormal conditions, and mechanical ventilation provide a pathway for oral microorganisms to enter the lower respiratory tract and thus cause respiratory disease. Lung hypoxia, typical symptoms of COVID-19, would favor the growth of anaerobes and facultative anaerobes originating from the oral microbiota. SARS-CoV-2 may aggravate lung disease by interacting with the lung or oral microbiota via mechanisms involving changes in cytokines, T cell responses, and the effects of host conditions such as aging and the oral microbiome changes due to systemic diseases. Because the oral microbiome is closely associated with SARS-CoV-2 co-infections in the lungs, effective oral health care measures are necessary to reduce these infections, especially in severe COVID-19 patients. 

Porphyromonas pasteri and Prevotella nanceiensis in the sputum are associated with increased decline in lung function in individuals with cystic fibrosis

 

The role of anaerobic bacteria  in disease progression in cystic fibrosis (CF) was studied by Webb et al. from UnitedKingdom.  The authors hypothesized that the presence and relative abundance of the most prevalent, live, anaerobic bacteria in sputum of adults with CF were associated with adverse clinical outcomes.

The investigators performed 16S rRNA analysis using a viability quantitative PCR technique on sputum samples obtained from a prospective cohort of 70 adults with CF and collected clinical data over an 8 year follow-up period. They examined the associations of the ten most abundant obligate anaerobic bacteria present in the sputum with annual rate of FEV1 change. The presence of Porphyromonas pasteri and Prevotella nanceiensis were associated with a greater annual rate of FEV1 change. Similarly, the relative abundance of these live organisms were associated with a greater annual rate of FEV1 decline of -3.7 ml yr-1 and -5.3 ml yr-1  for each log 2 increment of abundance, respectively.

The authors concluded that the presence and relative abundance of certain anaerobes in the sputum of adults with CF are associated with a greater rate of long-term lung function decline.

Diagnosis of orthopaedic-implant-associated infections caused by slow-growing Gram-positive anaerobed

 Slow-growing Gram-positive anaerobic bacteria (SGAB) such as Cutibacterium acnes are increasingly recognized as causative agents of implant-associated infections (IAIs) in orthopaedic surgeries. SGAB IAIs are difficult to diagnose because of their non-specific clinical and laboratory findings as well as the fastidious growth conditions required by these bacteria. A high degree of clinical suspicion and awareness of the various available diagnostic methods is therefore important. A review by Ponraj et al.  overviews the current knowledge regarding SGAB IAI, providing details about clinical features and available diagnostic methodologies. In recent years, new methods for the diagnosis of IAI were developed, but there is limited knowledge about their usefulness in SGAB IAI. The authors conclude that further studies are required to determine the ideal diagnostic methodology to identify these infections so that they are not overlooked and mistakenly classified as aseptic failure.

                                                   Cutibacterium acnes gram stain

Complications of Otitis Media and Sinusitis Caused by Streptococcus anginosus Group Organisms in Children.

McNeil et al. from Texas Children'sHospital studied 95 children seen between 2011 to 2018 with complications of otitis media and sinusitis caused by Streptococcus anginosus Group (SAG) organisms.  SAG are nonmotile facultative anaerobes that are part of the normal oral cavity, throat, stool, and vagina flora. Cases included were those with Pott's puffy tumor, orbital abscesses, mastoiditis, epidural abscesses, subdural empyema, brain parenchymal abscesses or dural enhancement by imaging.

Streptococcus intermedius was most commonly isolated (80%) followed by Streptococcus constellatus (12.6%) and Streptococcus anginosus (7.4%); 50.5% of cases were polymicrobial. Among polymicrobial cases, Staphylococcus aureus was most frequently isolated. All patients underwent surgical intervention and 8.4% had persistent neurologic deficits. Complications of otitis media and sinusitis caused by SAG are associated with substantial morbidity.

The researchers concluded that intraorbital and intracranial infections in general and SAG in particular are becoming increasingly common at their medical center.

Streptococcus anginosus (Gram stain)