Medical Director, Infection Prevention, El Camino Hospital, Palo Alto Medical Foundation
Plague in the 21st Century
SOURCE: Butler T. Plague gives surprises in the second decade of the twenty-first century. Am J Top Med Hyg 2023;109:985-988.
Butler nicely summarizes human cases of plague reported in the world literature from 2010-2019, and highlights several unique features and cases. During this 10-year period, 4,547 human cases of plague were reported around the world, the vast majority (97.3%) in African countries, particularly Madagascar and the Congo, with a minority of cases in Uganda and Tanzania. Most of the remaining cases occurred in Peru (n = 74) and the United States (n = 50). Case fatality rates ranged from 3% to 60%, with an overall combined death rate of 17%.
During this period of time, the four largest outbreaks occurred in Madagascar, resulting in a total of 1,936 cases (7.1% died). Of these, the 2017 outbreak was unusual, as it bounded through two large cities, including the coastal port of Toamasina and nearby Antananarivo. It started with a passenger in a cab leaving the coastal port — and the cab driver and subsequent passengers carried infection throughout the cities. This outbreak ostensibly affected 1,878 people, although only 32 cases eventually were confirmed, raising the obvious question of whether some of these suspect cases were due to other less morbid etiologies (especially given the lower mortality rate of 7.1%).
This 2017 outbreak also stands in contrast to most other cases around the world — the majority of which occur in small towns and villages and agricultural areas. Historically, 90% of plague cases in small towns and rural areas are bubonic, but many of the cases in these larger African outbreaks were pneumonic, with person-to-person spread in taxi cabs, households, at funerals, and in hospitals. Another smaller outbreak in 2013 in Madagascar involving 22 people was notable for a streptomycin-resistant strain. Nineteen people acquired infection at the funerals for the plague-deceased.
Fifty cases occurred in the United States from 2010-2019, including five deaths (10%). In reviewing Centers for Disease Control and Prevention (CDC) data and maps, which detail 116 cases in the United States from 2000-2020, the majority of cases in the United States occurred in four states (New Mexico, southern Colorado, Arizona, and California), with a smattering of cases from Utah, Texas, Nevada, and Idaho.1 Historically, 80% of U.S. cases are bubonic, and the vast majority occur in rural areas.
Three U.S. cases were more unusual:
• A cluster of four cases occurred in Colorado in 2014 when a dog owner developed pneumonia four days after his dog became ill with hemoptysis and was euthanized. Three other people were exposed to the dog, one of whom also had contact with the owner. These cases were unusual because dog respiratory droplets resulted in infection. Generally, we think of cats as a more common source of infection, with exposure to rodents and rodent fleas. The dog owner was lucky to have been treated within 24 hours of symptom onset, since pneumonic plague is virtually 100% fatal within 24 hours if untreated.
• A 14-year-old boy camping in Yosemite in 2015 developed severe septicemic plague after feeding campground squirrels. Within 10 days, he required hospitalization, and a week into his treatment was diagnosed with multifocal osteomyelitis involving the acetabulum, tibia, femur, and vertebral bodies, as well as septic arthritis of the right hip. The extensive bone and joint involvement in this case was unique. The campground was investigated, and both ground squirrels and chipmunks were seropositive for Yersinia pestis, and their fleas were polymerase chain reaction (PCR) positive. Next-generation sequencing confirmed the boy’s isolate was identical to isolates recovered at the campsite.
• In 2016, an effort to relocate prairie dogs, some of which were sick and dying, resulted in transmission from a prairie dog bite to worker (bit the thumb and finger). Within eight days, the worker developed axillary adenopathy and blood cultures were positive for Y. pestis. This case was unique because bubonic plague occurred as the result of a bite, presumably from infected oral secretions.
Reference
- Centers for Disease Control and Prevention. Plague. Maps and statistics. Last reviewed Nov. 16, 2022. https://www.cdc.gov/plague/maps/index.html
Vertebral Osteomyelitis from Staphylococcus aureus
SOURCE: Kinamon T, Dagher M, Park L, et al. Risk factors and outcomes of hematogenous vertebral osteomyelitis in patient with Staphylococcus aureus bacteremia. Clin Infect Dis 2023;77:1226-1233.
Researchers examined the risk factors and outcomes of vertebral osteomyelitis as part of a prospective cohort study of adults admitted with Staphylococcal aureus bacteremia (SAB) at Duke University from 2015-2019. During this period, 3,165 adults were admitted with SAB, 145 of whom were diagnosed with vertebral osteomyelitis. Eighteen patients were excluded for post-operative or peri-procedural infections, leaving a total of 127 cases of vertebral osteomyelitis (4%) associated with SAB. Race, gender, and age were similar between SAB patients with and without vertebral osteomyelitis.
The lumbar spine was affected most commonly. SAB patients who were diagnosed with vertebral osteomyelitis were more likely to have community-acquired vs. nosocomially acquired bacteremia (31% vs. 16.7%); they were more likely to have a history of injection drug use (14.2% vs. 5.5%); and they were more likely to have an unknown source for their infection (37.8% vs. 19.1%). SAB with vertebral osteomyelitis also was associated with a greater diagnostic delay (median five days). These patients also were more likely to have persistent bacteremia ( ≥ 5 days of effective therapy) compared to those without vertebral involvement (48.8% vs. 20.6%). They also were more likely to have endocarditis than those without vertebral involvement (26% vs. 15.2%). Interestingly, no increased risk for vertebral osteomyelitis was observed among SAB patients with methicillin-resistant strains compared with methicillin-sensitive strains.
One-fourth of those with SAB and vertebral osteomyelitis required surgical intervention, with most of these for epidural abscess (75%). Patients requiring surgery were more likely to have neurologic consequences compared with non-surgical patients, including weakness (54.5% vs. 25%), sensory loss (30% vs. 6.4%), and neurologic deficits on examination (60.6% vs. 23.2%). Surgical patients generally were treated with a longer course of antibiotics (median 92 days), compared with non-surgical patients (median 64 days); and 20% of surgical patients remained on antibiotics at one year (57% of those because of retained hardware).
Outcomes for adults with SAB-associated vertebral osteomyelitis were surprisingly poor. At least 64% required readmission within a year, and nearly one-third (30%) developed recurrent vertebral infection and/or recurrent SAB. All-cause mortality at 90 days was 14% and at one year was 22%. All-cause mortality was similarly bad whether surgery was required or not. Vertebral osteomyelitis from S. aureus is a debilitating and highly morbid condition.
Rifampin in Vertebral Osteomyelitis Is Useful
SOURCE: El Zein S, Berbari EF, Passerini M, et al. Rifampin based therapy for patients with Staphylococcus aureus native vertebral osteomyelitis: A systemic review and meta-analysis. Clin Infect Dis 2023;Sept 18:ciad560. doi10.1093/cid/ciad560. [Online ahead of print].
Rifampin frequently is used as adjuvant antibacterial therapy in Staphylococcus aureus bone infection, based on its ability to get into biofilms and treat intracellular bacteria. The authors performed a meta-analysis of the use of rifampin as adjuvant treatment in native vertebral osteomyelitis secondary to Staphylococcus aureus. The authors performed a literature search for the use of rifamycins and rifampin in the treatment of vertebral bone infection, and identified 13 publications, including 11 comparative cohort studies and two randomized clinical trials. All 13 studies used rifampin, and none used other rifamycins or rifabutin.
The 13 studies included a total of 679 patients with native vertebral osteomyelitis secondary to S. aureus. Of these, 435 (64%) did not receive rifampin as adjuvant therapy and 244 (36%) did. The primary treatment varied widely from glycopeptides, to beta lactams, and fluoroquinolones, and less commonly daptomycin, tetracycline, and trimethoprim-sulfamethoxazole. Rifampin was used at a dosage of either 600 mg or 900 mg daily, generally at either 300 mg or 450 mg twice daily, for a median duration of 42 days (six weeks). Because many of these studies were European, the combination of fluoroquinolone and rifampin was used commonly. The use of rifampin was associated with a 14% absolute risk reduction in clinical failure (P < 0.001). Overall, clinical failure occurred in 38 (15.6%) of the rifampin group and 95 (21.8%) of the standard-of-care (non-rifampin) group. A subgroup analysis demonstrated a lower risk of treatment failure using a combination of a fluoroquinolone plus rifampin compared with other combinations.
Of those patients with available blood culture results, 90.5% were bacteremic with positive blood cultures for S. aureus at the time of the vertebral osteomyelitis diagnosis. While the timing of rifampin administration is always a question, this information in relation to the onset of bacteremia was not available. The risk of adverse effects from rifampin use also was not available. The authors commented that the overall risk of rifampin-resistant S. aureus is increasing (up to 6% in the United States), although it was only 1% at their institution.