By Carol A. Kemper, MD, FACP

Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases, Santa Clara Valley Medical Center

Pyrethroids Losing Activity Against Mosquitoes

SOURCE: Keïta M, Sogoba N, Kané F, et al. Multiple resistance mechanisms to pyrethroids insecticides in Anopheles gambiae sensu lato population from Mali, West Africa. J Infect Dis 2021;223(Suppl 2):S81-S90.

Pyrethroid-impregnated mosquito netting and indoor dusting/spraying have been critical steps in malaria control in Africa. The increased use of these measures, coupled with indiscriminate agricultural use, has increased the selection pressure on mosquito vectors, with loss of pyrethroid activity in some areas. Using the World Health Organization standard bioassay to assess Anopheles gambiae sensu lato susceptibility to pyrethroids, these authors examined both phenotypic and genotypic resistance mechanisms in three different health districts in Mali, West Africa.

High frequencies of phenotypic resistance to both deltamethrin and permethrin was found in Anopheles gambiae s.l. in multiple locations, with only 13% to 41% mortality observed. Susceptibility to deltamethrin could be partially restored by the addition of piperonyl butoxide (PBO) (a P450 cytochrome inhibitor) and, to a lesser degree, two other metabolic inhibitors, suggesting the presence of three different metabolic resistance pathways.

Taqman SNP genotyping assays for targeted markers showed a high prevalence of previously recognized Kdr_W resistant alleles at all of the study sites, including a high frequency of L1014F, L1014S, and 1575Y gene mutations. These data suggest that multiple genotypic and metabolic mechanisms for resistance are simultaneously developing in the mosquito population in West Africa, requiring an updated and comprehensive strategy for mosquito vector control.


Resistance Erodes Standard Treatment for Pneumonia

SOURCE: Haessler S, Lindenauer PK, Zilberberg MD, et al. Blood cultures versus respiratory cultures: 2 different views of pneumonia. Clin Infect Dis 2020;71:1604-1612.

To examine whether current guidelines for the treatment of pneumonia remain appropriate, researchers conducted a large multicenter study of adults with pneumonia admitted to 177 United States hospitals between 2010 and 2015. Patients admitted with a principal diagnosis of pneumonia, respiratory failure, acute respiratory distress syndrome, or sepsis with a secondary diagnosis of pneumonia, and who also had blood and/or respiratory cultures obtained on admission were included in the analysis. A total of 138,561 hospitalizations met criteria, of which about two-thirds were considered community-acquired pneumonia (CAP) (68%) and one-third was deemed healthcare-associated pneumonia (HCAP) (32%).

Blood cultures were obtained on admission in 99% of hospitalizations and respiratory cultures were obtained in 18%. Positive cultures were infrequent: Only 9.3% of all admissions had a positive culture, including 4.6% with a positive respiratory culture alone, 4.3% with a positive blood culture alone, and 0.3% with both positive respiratory and blood cultures. In those able to produce a sputum specimen, respiratory cultures were positive in 28%, and patients with HCAP were more likely than those with CAP to have a positive sputum culture (33% vs. 25.4%, P < 0.001). Of all the blood cultures obtained, only 4.7% were positive.

Among those with positive blood cultures alone, Streptococcus pneumonia (33%) and Staphylococcus aureus (22%) were the most common organisms isolated, followed by Escherichia coli (11.8%), Klebsiella spp. (4.6%), Pseudomonas aeruginosa (3.5%), group B strep (2.7%), Haemophilus influenzae (2%), and Proteus mirabilis (1.6%). More than one-third of S. aureus bacteremias were methicillin-resistant (36%). In contrast, in those with only positive respiratory cultures, S. aureus (33.6%) and Pseudomonas aeruginosa (17%) were the most common isolates. In those with both positive blood and respiratory cultures, S. aureus was more common (44.5%) (41% was methicillin-resistant), followed by S. pneumoniae (32%) and Pseudomonas aeruginosa (7.7%).

The prevalence of resistance to recommended first-line CAP antibiotics (i.e., ceftriaxone plus azithromycin or a respiratory quinolone) was assessed by organism and by culture site. Two hundred nine patients were excluded because their organisms lacked clear Clinical & Laboratory Standards Institute (CLSI) breakpoints. Overall, 42% of admissions with a positive culture grew an organism resistant to first-line therapy for CAP, including 27% of those with positive blood cultures. Gram-negative organisms isolated in either blood or respiratory cultures were more likely to be resistant to CAP therapy than gram positives (51.8% vs. 35.4%). Patients with only positive respiratory cultures were twice as likely to yield organisms resistant to CAP therapy, but their outcomes were better, suggesting that some of these organisms represented colonizers rather than true pathogens.

Although two-thirds of the patients in this study were considered to have CAP and one-third HCAP, empirical antibiotic therapy administered at the time of admission did not necessarily reflect these designations. For those patients with only positive respiratory, only positive blood, or both positive respiratory and blood cultures, anti-methicillin-resistant S. aureus (MRSA) antibiotics were administered to 42%, 48%, and 66% (P < 0.001). Similarly, HCAP-guideline antibiotics were administered in 11.8%, 15.7%, and 27%, respectively, and four or more antibiotics were administered in 17.5%, 21%, and 33%, respectively. This suggests that providers were cognizant of the severity of disease at presentation and the risk of MRSA and multidrug-resistant organisms (MDRO) in some patients.

Despite these efforts, patients with both positive blood and sputum cultures generally had more acute and chronic illness, with significantly higher case fatality rates (25%) than those patients with only positive blood (12%) or respiratory cultures (11%); and they had significantly longer lengths of stay.

Predicting the bacterial etiology of pneumonia on presentation to the hospital, when empirical antibiotic therapy must be chosen, is challenging — and the choice depends on many factors, including the acuity of the presentation, chronicity of underlying disease, recent residence in long-term care, and the anticipated flora. Not mentioned in this article is the benefit of “flagging” those patients with recognized MDROs from prior cultures in an electronic computer system, as well as the use of nares MRSA polymerase chain reaction (PCR) to identify those patients at risk for MRSA pneumonia. These data suggest that CAP therapy may no longer be relevant for many patients with CAP, and the required use of the current CAP bundle with limited antibacterial therapy choices should be re-assessed. 


Homelessness and COVID-19

SOURCE: Cha S, Henry A, Montgomery MP, et al. Morbidity and mortality among adults experiencing homelessness hospitalized with COVID-19. J Infect Dis 2021;224:425-429.

These authors examined risk factors and outcomes for homeless adults admitted to an acute care hospital with COVID-19. Using the COVID-NET population-based surveillance system for acute care hospitalizations in 10 different states, plus the Influenza Hospital Surveillance Project for four additional states, data on laboratory-confirmed COVID-19 hospitalizations were collected. Among nearly 29,000 hospitalizations, only 8,728 cases had sufficient documentation regarding housing at the time of admission. Of these, 199 were homeless adults. The median age was 53 years, and 84% were Black, Latino, or other non-Hispanic other race/ethnicity. Most of the patients (83%) had at least one significant health condition, 32% had diabetes, and 24% were considered obese; tobacco use (46%) and alcohol abuse (34%) were common; and 8% had mental health issues.

A majority (54%) of these homeless patients were hospitalized for > 4 days, 17% were admitted to the intensive care unit (ICU), and 11% required mechanical ventilation. Six patients died (3%), five of whom were 50 years of age or older. As has been observed previously, disease severity was associated with increasing age.

Despite the anticipated poor outcomes, I was surprised that this homeless cohort did as well as they did. Mortality for COVID-19 cases admitted to the hospital early on during the pandemic was reportedly as high as 12% to 18%. A large 2020 study of 11,210 COVID-19 admissions to 92 acute care hospitals across 12 states (many of which were included in this homeless study) found an all-cause mortality of 20.3%, and 31.8% required mechanical ventilation.1

More recent data suggest that hospital mortality from COVID-19 may have improved. In a large 2021 study of 192,550 adult hospitalizations with COVID-19 at 555 acute care hospitals in the United States, 13.6% of adults died during the index hospitalization and another 3% were transitioned to hospice care.2 Since February 2020, our community hospital in Mountain View, CA, has provided care for 1,000 COVID-19 patients, with an overall mortality of 9.3%. One-fourth of admissions required ICU care and one-fourth of those died. That the homeless cohort in this study had much better outcomes than any of these data suggests they may have been admitted for other complicating health reasons or perhaps for psychosocial concerns.

The COVID-19 pandemic has heightened the need for better care and planning for homeless persons. Persons who are homeless, especially those who reside in camps or shelters, are at increased risk for COVID-19 infection; their hygiene, dentition, and general health suffer as the result of their homelessness, and their poor health belies their years, putting them at risk for more severe COVID-19. It also makes COVID-19 discharge planning a challenge; thankfully, our Public Health Department has invested in several “COVID hotels” with private rooms, hot showers, and meals as needed.

A first step would be screening for homeless status on admission to any acute care hospital. Only 30% of admissions identified in this study had adequate documentation of housing. In January 2019, California Senate Bill 1152 was created, requiring acute care hospitals to screen for homelessness on admission and to offer appropriate vaccinations, such as hepatitis A and influenza, as well as screening for appropriate infectious diseases, such as human immunodeficiency virus, hepatitis B, and tuberculosis. Originally intended to halt an outbreak of hepatitis A in the homeless populations in several California counties, this extra screening step in care for homeless persons is helping to solve many problems, including the administration of COVID-19 vaccination to this vulnerable population.

REFERENCES            

  1. Yehia BR, Winegar A, Fogel R, et al. Association of race with mortality among patients hospitalized with coronavirus disease 2019 (COVID-19) at 92 US hospitals. JAMA Netw Open 2020;3:e2018039. 
  2. Nguyen NT, Chinn J, Nahmias J, et al. Outcomes and mortality among adults hospitalized with COVID-19 at US medical centers. JAMA Netw Open 2021;4:e210417.