Acinetobacter nosocomialis Causes as Severe Disease as Acinetobacter baumannii in Northeast Thailand: Underestimated Role of A. nosocomialis in Infection.

Infections by Acinetobacter species are recognized as a serious global threat due to causing severe disease and their high levels of antibiotic resistance. Acinetobacter baumannii is the most prevalent pathogen in the genus, but infection by Acinetobacter nosocomialis has been reported widely. Diagnosis of patients with A. baumannii infection is often misdiagnosed with other Acinetobacter species, especially A. nosocomialis. This study investigated whether there were significant differences in clinical outcomes between patients infected with A. baumannii versus A. nosocomialis in Northeast Thailand, and to characterize serological responses to infection with these pathogens. The results show that A. baumannii had higher levels of multidrug resistance. Despite this, clinical outcomes for infection with A. baumannii or A. nosocomialis were similar with mortalities of 33% and 36%, respectively. Both pathogens caused community-acquired infections (A. baumannii 35% and A. nosocomialis 29% of cases). Plasma from uninfected healthy controls contained IgG antibody that recognized both organisms, and infected patients did not show a significantly enhanced antibody response from the first week versus 2 weeks later. Finally, the patterns of antigen recognition for plasma IgG were similar for patients infected with A. baumannii or A. nosocomialis infection, and distinct to the pattern for patients infected with non-Acinetobacter. In conclusion, our data revealed that infection with A. nosocomialis was associated with a similarly high level of mortality as infection with A. baumannii, the high rate of community-acquired infection and antibodies in uninfected individuals suggesting that there is significant community exposure to both pathogens. IMPORTANCE Bacterial infections by Acinetobacter species are global threats due to their severity and high levels of antibiotic resistance. A. baumannii is the most common pathogen in the genus; however, infection by A. nosocomialis has also been widely reported but is thought to be less severe. In this study, we have prospectively investigated 48 reported cases of A. baumannii infection in Northeast Thailand, and characterized the serological responses to infection. We found that 14 (29%) of these infections were actually caused by A. nosocomialis. Furthermore, the incidence of antibiotic resistance among A. nosocomialis strains, APACHE II scores, and mortality for patients infected with A. nosocomialis were much higher than published data. Both A. baumannii and A. nosocomialis had unexpectedly mortality rates of over 30%, and both pathogens caused a high rate of community-acquired infections. Importantly, background antibodies in uninfected individuals suggest significant community exposure to both pathogens in the environment

Epidemiology and antimicrobial resistance of invasive non-typhoidal Salmonellosis in rural Thailand from 2006-2014

<div><p>Introduction</p><p>Invasive salmonellosis is a common cause of bloodstream infection in Southeast Asia. Limited epidemiologic and antimicrobial resistance data are available from the region.</p><p>Methods</p><p>Blood cultures performed in all 20 hospitals in the northeastern province of Nakhon Phanom (NP) and eastern province of Sa Kaeo (SK), Thailand were captured in a bloodstream infection surveillance system. Cultures were performed as clinically indicated in hospitalized patients; patients with multiple positive cultures had only the first included. Bottles were incubated using the BacT/Alert system (bioMérieux, Thailand) and isolates were identified using standard microbiological techniques; all <i>Salmonella</i> isolates were classified to at least the serogroup level. Antimicrobial resistance was assessed using disk diffusion.</p><p>Results</p><p><i>Salmonella</i> was the fifth most common pathogen identified in 147,535 cultures with 525 cases (211 in Nakhon Phanom (NP) and 314 in Sa Kaeo (SK)). The overall adjusted iNTS incidence rate in NP was 4.0 cases/100,000 person-years (95% CI 3.5–4.5) and in SK 6.4 cases/100,000 person-years (95% CI 5.7–7.1; p = 0.001). The most common serogroups were C (39.4%), D (35.0%) and B (9.9%). Serogroup D predominated in NP (103/211) with 59.2% of this serogroup being <i>Salmonella</i> serovar Enteritidis. Serogroup C predominated in SK (166/314) with 84.3% of this serogroup being <i>Salmonella</i> serovar Choleraesuis. Antibiotic resistance was 68.2% (343/503) for ampicillin, 1.2% (6/482) for ciprofloxacin (or 58.1% (280/482) if both intermediate and resistant phenotypes are considered), 17.0% (87/512) for trimethoprim-sulfamethoxazole, and 12.2% (59/484) for third-generation cephalosporins (cefotaxime or ceftazidime). Multidrug resistance was seen in 99/516 isolates (19.2%).</p><p>Conclusions</p><p>The NTS isolates causing bloodstream infections in rural Thailand are commonly resistant to ampicillin, cefotaxime, and TMP-SMX. Observed differences between NP and SK indicate that serogroup distribution and antibiotic resistance may substantially differ throughout Thailand and the region.</p></div

Age distributions for the major serogroups of invasive non-typhoidal <i>Salmonella</i> in Nakhon Phanom and Sa Kaeo provinces.

<p>Age distributions for the major serogroups of invasive non-typhoidal <i>Salmonella</i> in Nakhon Phanom and Sa Kaeo provinces.</p

Antibiotic resistance among invasive non-typhoidal <i>Salmonella</i> isolates by province and year.

<p>Solid line graph shows number of positive blood cultures and the dashed line indicates the total number of bottles incubated by year (z-axis). TMP-SMX = trimethoprim-sulfamethoxazole.</p

Flow diagram of blood culture data identifying non-typhoidal Salmonella cases, Nakhon Phanom and Sa Kaeo provinces, 2006-2014.

<p>Blood culture bottles were incubated at 35°C for up to 5 and 42 days (F and MB bottles respectively), or until the instrument signaled positive for growth (i.e., positive signal). Culture bottles that did not signal positive after the specified incubation periods (no signal) were considered to be negative without terminal subculture. A. The following organisms were considered likely contaminants and not included in the analysis: S<i>treptococcus viridans</i> group, <i>Corynebacterium</i> spp., <i>Bacillus</i> spp. (other than <i>B</i>. <i>anthracis</i>), <i>Staphylococcus</i> spp. (other than <i>S</i>. <i>aureus</i>), and <i>Aerococcus</i> spp. B. The unknown category were non-identifiable isolates using our standard biochemical testing including Gram-positive and negative cocci (n = 197 and 11 respectively), and Gram-positive bacilli (n = 343); these are likely contaminants. Gram-negative bacilli (n = 12) and unknown other (n = 708). C. The automated blood culture instrument signaled positive, but subculture yielded no organism.</p

Epidemiology and antimicrobial resistance of invasive non-typhoidal Salmonellosis in rural Thailand from 2006-2014 - Fig 3

<p><b>Incidence of invasive non-typhoidal Salmonellosis by age group and year in Sa Kaeo (SK, left) and Nakhon Phanom (NP, right) provinces, 2006–2014.</b> RR = relative risk, measured differences between SK and NP. Relative risk is given with upper and lower 95% confidence intervals. * designates age group differences between NP and SK within the specified year (p-value < 0.05) and likely to be driving the differences.</p

Distribution of invasive non-typhoidal Salmonella serovars isolated in two rural Thai provinces between 2006 and 2014.

<p>Distribution of invasive non-typhoidal Salmonella serovars isolated in two rural Thai provinces between 2006 and 2014.</p

Map of Thailand showing the two rural provinces, Nakhon Phanom (NP) and Sa Kaeo (SK), participating in population-based bloodstream surveillance.

<p>The enlarged map of each province details the number of invasive non-typhoidal Salmonella (iNTS) cases for each hospital as indicated by the size of circle in each district. The color of the marker represents the number of beds for each hospital (the darker the color the higher the number of beds: range from 10–306). Map generated using ArcGIS version 10.5.1, (Environmental Systems Research Institute, Redlands, CA, USA); the base-layer country map was from the ArcGIS software and provincial level overlay file was obtained from the Ministry of Land, Thailand. Donut diagrams show the distribution of iNTS serogroups isolated in each province from 2006 to 2014.</p

Antimicrobial susceptibility^a profiles for non-typhoidal <i>Salmonella</i> isolates by serogroup and province.

<p>Antimicrobial susceptibility<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006718#t003fn002" target="_blank">^a</a> profiles for non-typhoidal <i>Salmonella</i> isolates by serogroup and province.</p

Association of discharge diagnosis and serogroup with case outcome among patients with invasive non-typhoidal Salmonellosis.

<p>Association of discharge diagnosis and serogroup with case outcome among patients with invasive non-typhoidal Salmonellosis.</p