Community-Acquired Hafnia paralvei Pneumonia in an Immunocompetent Adult: A Case Report, Genomic Characterization of Antimicrobial Resistance, and Literature Review

Abstract

Background. Hafnia alvei is considered an uncommon pathogen in immunocompetent individuals. It has been isolated in several cases of nosocomial pneumonia, but it has rarely been associated with community-acquired pneumonia (CAP) in immunocompetent adults. In 2010 a genotypically distinct species of Hafnia was identified, for which the name Hafnia paralvei was proposed. Since then, very few cases of human infection by H. paralvei have been reported. We describe here a case of CAP sustained by H. paralvei in a man without major systemic comorbidities and the genomic characterization of antibiotic resistance, together with a review of the literature on this topic. Case presentation. A 54-year-old man was admitted to the Emergency Room (ER) with a 3-day history of fever, fatigue, nausea. In the ER a thoracic CT scan revealed an extensive area of consolidation in the left lower lobe. He was empirically treated with piperacillin/tazobactam + azithromycin. After an initial improvement, clinical conditions worsened and empirical therapy was changed to meropenem + linezolid. An aerosol-induced sputum for bacterial culture yielded Hafnia alvei 10⁷ colony-forming-units/mL; the germ was resistant to piperacillin/tazobactam and was sensitive to ceftriaxone, cefepime, and meropenem. Therefore, linezolid was withdrawn and meropenem continued obtaining resolution of the pneumonia. During the revision process, in silico analysis of sequences using three independent genome-based methods was performed: all three approaches, each relying on a different taxonomic metric, consistently assigned the isolate to H. paralvei. Moreover, the study of resistance-associated genes showed that the isolate harbored bla_ACC-1a and bla_mcr-9.1. Conclusions. We have described a case of CAP due to H. paralvei in an immunocompetent man. Limitations in antibiotic choices and duration of treatment have been discussed, and genomic characterization of antibiotic resistance has been studied.

1. Introduction

Hafnia alvei is a Gram-negative, facultative anaerobic, rod-shaped bacterium belonging to the family Hafniaceae within the order Enterobacterales; it was formerly named Enterobacter hafniae [1]. Sources from which H. alvei can be recovered include mammals, birds, reptiles, soil, water, sewage, and food. Historically, it was occasionally isolated from the intestine of honeybees and from honey, whence the epithet alvei, derived from the Latin “alveus”, meaning beehive. The genus name Hafnia comes from the historical name (Havn) for the city of Copenhagen, Denmark [2].

H. alvei is an uncommon human pathogen. It has been reported as the cause of gastroenteritis, bacteremia, pneumonia, urinary tract infection, wound infection and, more rarely, meningitis, endophthalmitis, abscesses, and septic arthritis [2,3,4,5,6,7,8,9,10].

H. alvei is seldom considered pathogenic in immunocompetent individuals; however, it is known to be responsible for serious nosocomial and community-acquired infections, mainly in patients with underlying diseases or immunosuppression [1]. H. alvei has been isolated in several cases of nosocomial pneumonia [11,12,13,14,15,16], but it has rarely been associated with community-acquired pneumonia (CAP) in immunocompetent adults [17,18,19,20,21,22].

Until 2010 H. alvei was the only recognized species in the genus Hafnia, although DNA–DNA hybridization studies had previously revealed that H. alvei was genetically heterogeneous and consisted of at least two DNA hybridization groups (HGs), with HG 1 representing H. alvei sensu stricto, by convention. In 2010 Huys and coll [23] found that strains formerly classified as members of H. alvei HG 2 represented a novel species, for which the name Hafnia paralvei was proposed. Since then, very few cases of human infection by H. paralvei have been reported. Moreover, it is possible that strains previously identified as H. alvei could have actually been H. paralvei.

We describe here a case of CAP sustained by H. paralvei in an immunocompetent man and the genomic characterization of antibiotic resistance, together with a review of the literature on this topic.

2. Methods

Preliminary species identification and antimicrobial susceptibility was performed by MALDI-TOF Biotyper System (Bruker Daltonics, Bremen, Germany) and Phoenix system (Becton Dickinson Diagnostics, San Diego, CA, USA), respectively. Determination of minimum inhibitory concentrations (MICs) for colistin was obtained through broth microdilution (Liofilchem, Roseto degli Abruzzi, Italy). Results were interpreted according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines (http://www.eucast.org/clinical_breakpoints/) (accessed on 6 August 2026). Whole-genome sequencing (WGS) was achieved on Illumina Miseq platform (Illumina, San Diego, CA, USA). Quality control of raw reads was performed using FastQC v0.11.9, followed by read trimming with Trimmomatic v0.39 in paired-end mode. Trimmed reads were assembled de novo using Unicycler v0.5.1. Assembly quality was assessed using QUAST v5.3.0 and BUSCO v5.8.2. The resulting genome assembly was used to further confirm the taxonomic assignment of the isolate using three independent genome-based approaches. Pathogenwatch was used for preliminary species identification based on Mash distance analysis (https://pathogen.watch) (accessed on 6 August 2026). Species assignment was subsequently confirmed using the Type (Strain) Genome Server, which performs genome-wide taxonomic comparisons and digital DNA–DNA hybridization (dDDH, formula d4) analyses against reference type strains. Species delineation was assessed using the 70% dDDH threshold (https://tygs.dsmz.de/) (accessed on 6 August 2026). Finally, GTDB-Tk v2.7.2 with the GTDB reference database vr232 was used to independently verify species designation through genome-based taxonomic classification and average nucleotide identity (ANI) analysis according to the GTDB species circumscription framework (95% ANI threshold) (https://github.com/ecogenomics/gtdbtk) (accessed on 6 August 2026). Antimicrobial resistance genes were extracted from the WGS data and identified by in silico analysis using the ResFinder v3.0 web server (http://www.genomicepidemiology.org) (accessed on 6 August 2026). The minimum percentage of sequence identity was set at 100%, with an alignment length of >98%. Raw reads were submitted to the Sequence Read Archive (SRA) under the BioProject PRJNA1474296.

We made a search in Pubmed using as keywords “Hafnia alvei” AND “pneumonia” (last accessed 6 August 2026) and obtained 80 papers, among which 12 described cases with H. alvei pneumonia. Seven more reports were found by examining the references of the above-mentioned papers. Abstracts without full case information were included and no language restriction was used. We considered attributable to H. alvei the reported cases of pneumonia, in addition to the clinical judgment of the Authors, when H. alvei was reported as isolated from respiratory specimens. We considered a pneumonia as community-acquired if diagnosed on admission or <48 h from hospital admission, and hospital-acquired if developed in patients admitted to the hospital for >48 h. A pneumonia was considered ventilator-associated if developed in patients who had been mechanically ventilated for at least 48 h.

Moreover, during the revision process, when the Hafnia strain of our patient was found to be a H. paralvei, we made a new search in Pubmed using as keyword simply “Hafnia paralvei” (last accessed 12 October 2026) and obtained 45 papers; only 5 papers reported human cases. Abstracts without full case information were included and no language restriction was used.

3. Case Report

A 54-year-old man was admitted to the Emergency Room (ER) with a 3-day history of fever (maximum 40.2 °C), fatigue, nausea. He was free of major systemic comorbidities. In the ER a thoracic CT scan revealed an extensive area of consolidation with pleural effusion in the left lower lobe. Blood tests showed the following: white blood cells (WBC) 8200/mm³, hemoglobin 13 g/dL, platelets (PLT) 232,000/mm³, C-reactive protein (CRP) 26 mg/dL, procalcitonin 0.22 ng/mL. Urinary antigens of Legionella and S. pneumoniae were absent. A multiplex polymerase chain reaction (PCR) for respiratory pathogens was negative in naso-pharyngeal swab. A Quantiferon TB test was positive. Blood cultures were negative. A transthoracic echocardiography was negative for endocarditis. In the ER, the patient received antibiotic therapy with piperacillin/tazobactam 4.5 g three times/day (TID) for 2 days (on days −3 and −2) and subsequently clarithromycin 500 mg two times/day (BID) + meropenem 1 g TID + linezolid 600 mg BID for 2 more days (on days −1 and 0). The patient was then transferred to our Center.

On admission (day 0) the patient was alert, oriented and eupneic; body temperature was 37.5 °C, blood pressure 120/80, heart rate 81/m, respiratory rate 18/m and oxygen saturation 94% in room air. Physical examination revealed reduced vesicular murmur with hypophonesis in the lower third of the left hemithorax. A blood gas analysis in room air showed pO2 67 mmHg, P/F 319. Oxygen was administered through nasal cannulas 2 L/m. Blood tests results were as follows: WBC 9040/mm³, hemoglobin 12.8 g/dL, PLT 281,000/mm³, glucose 108 mg/dL, creatinine 1.2 mg/dL, aspartate aminotransferase 44 U/L, alanine aminotransferase 57 U/L, CRP 22.3 mg/dL. Antibiotic therapy was prescribed consisting of piperacillin/tazobactam 4.5 g four times/day + azithromycin 500 mg once a day (on days +1 to +4). On day 3 the patient was afebrile and eupneic, WBC 8210/mm³ and CRP 7.3 mg/dL. Due to the positive result of the Quantiferon TB test performed in the ER, we prescribed an aerosol-induced sputum for bacterial culture and research of Mycobacterium tuberculosis.

On day 5 the clinical conditions slightly worsened with mild fever (37.5 °C) and fatigue; the WBC count increased to 13,220/mm³ and the CRP was 12 mg/dL. The thoracic CT scan showed consolidation of the left lower lobe with ipsilateral pleural effusion and a linear opacity in the right lower lobe (Figure 1a). Empirical antibiotic therapy was changed to meropenem 1 g TID + linezolid 600 mg BID on days +5 and +6. On day +7 we obtained the results of the aerosol-induced sputum tests: the search for M. tuberculosis was negative on direct examination and by PCR, but the culture grew Hafnia alvei 10⁷ colony-forming units/mL; the germ was resistant to piperacillin/tazobactam and amoxicillin/clavulanate and was sensitive to ceftriaxone, cefepime, and meropenem. Thereafter, linezolid was withdrawn and meropenem continued until day +19.

Figure 1. Evolution of the pleuropulmonary lesions. Chest CT scans showing the evolution of the pleuropulmonary lesions in our patient with H. paralvei pneumonia on day +5 (a), +16 (b), and +78 (c) from hospital admission.

The patient’s clinical conditions gradually improved and oxygen therapy was withdrawn. On day +16 a new thoracic CT scan revealed a reduction in the consolidation in the left lower lobe with a slight increase in the ipsilateral pleural effusion (Figure 1b). The blood tests showed WBC 4680/mm³ and CRP 0.33 mg/dL. A repeated Quantiferon TB test was negative. On day +19 a dental CT scan showed a marked horizontal resorption of the alveolar bone, particularly affecting the lower jaw. The patient did not report oral pain or recent dental care. On the same day, the patient was discharged and advised to see his dentist.

On day +78 a follow-up thoracic CT scan showed a residual small nodular consolidation (mm 14 × 9) in the posterior-basal segment of the left lower lobe (Figure 1c).

During the revision process for publication of this paper, the Hafnia strain isolated in our patient was subsequently found to be H. paralvei.

4. Discussion

H. alvei is often considered a colonizing enterobacterium. It has been recovered from oropharyngeal specimens, from the gastrointestinal tract, less often from blood and from other anatomic sites including airways, urine, soft tissue, and catheters. However, it has rarely been reported as a pathogenic organism [2,22]. For decades, H. alvei has been presumably associated with diarrheal disease even in outbreak settings [24,25,26,27], but its causative role has been questioned. Probably the first report linking H. alvei to human illness is a 1967 case report of bacteremia with fever and hypotension occurring in a man operated for a duodenal ulcer; the patient was successfully treated with oxytetracycline [2,28]. Subsequently, several reports described asymptomatic colonization or infections due to H. alvei; transmission was thought to be mainly nosocomial in one study [29] and community-acquired in another [30]. Sites of infection included the biliary tree, psoas abscess, appendix, prosthetic endocarditis, the urinary and respiratory tract. In the largest series of cases, H. alvei was isolated from 80 samples collected from 61 patients: 38 from respiratory specimens, 16 and 12 from the gastrointestinal and urogenital tract respectively, 8 from blood, 3 from intravenous catheters and from the skin [1]. Only 25% of all H. alvei isolates grew in pure culture; in the remaining cases it was cultured with a variety of other bacteria and fungi. Of 61 patients, 57 had underlying conditions including malignancies, abdominal and heart surgery, pancreatitis, trauma, chronic obstructive pulmonary disease, and lung transplantation. Six patients were judged to have true H. alvei infection, three nosocomial and three community-acquired: they all recovered with antibiotic therapy chosen according to the results of susceptibility testing [1]. When H. alvei was isolated in pure culture or as predominant germ there was a better correlation with disease status [29].

To date, we retrieved from the medical literature 19 reports on H. alvei pneumonia (Table 1) in 30 patients. Nine out of nineteen papers described patients with CAP and in just three cases the patient was otherwise healthy. All of the patients with CAP (for whom outcome is reported) recovered from the pneumonia. The vast majority of patients with H. alvei pneumonia had underlying diseases:

Table 1. Cases of H. alvei pneumonia. 

Reference	Year	N. of Patients	Gender & Age (y)	CAP/HAP/ VAP	Specimen	Underlying Diseases	Antibiotic Treatment	Outcome
Washington et al. [29]	1971	2	M 70, M 57	HAP HAP	Sputum Trachea	Melanoma COPD	NA °	Dead °
Frick et al. [11]	1990	2	NA	HAP °	NA	Cardiovascular surgery	Netilmicin ° imipenem °	Recovered °
Klapholz et al. [16]	1994	1	F 68	HAP	BAS	COPD, CKD, CHF	Aztreonam	Recovered
Gunthard et al. [1]	1996	1	NA	NA	NA	NA	NA	Recovered
Fazal et al. [18]	1997	1	F 54	CAP	Pleural fluid, sputum, blood	HIV	Tic/cla, Amoxi/cla	Recovered
Galeas et al. [21]	2001	1	F 25	CAP	Sputum	HIV	Ceftriaxone	Recovered
Hidalgo Tenorio et al. [31]	2002	1	M 46	HAP	Sputum	COPD, pulmonary tuberculosis	Ceftriaxone	Recovered
Millan Rodriguez et al. [15]	2003	2	M 78, M 73	HAP HAP	Sputum Sputum	COPD, diabetes COPD	Levo Cipro, Ceftriaxone	Recovered Recovered
Redondo et al. [13]	2005	1	M 85	HAP	Blood, RSA	COPD, abdominal surgery	NA	Dead
Loya et al. [32]	2015	1	F 95	CAP	Pleural fluid	CKD, Bonnet syndrome	Pip/taz, Cipro	Recovered
Karamanli et al. [33]	2017	1	M 58	CAP	Sputum	COPD	Ampi/s, Meropenem	Recovered
Baral et al. [34]	2018	1	M 11 mo	CAP	Blood	No	cefotaxime	Recovered
Begbey et al. [19]	2020	2	F 73, M 20	CAP CAP	Sputum BAL	COPD Crohn	Amoxi/cla, ceftazidime Amoxi/cla, Cipro, cotrimox	Recovered Recovered
Cutuli et al. [12]	2021	1	M 52	VAP	BAL	COVID-19	Meropenem	Recovered
Blonz et al. [35]	2021	8 isolates *	NA	VAP	NA	COVID-19	NA	NA
Severiche-Bueno et al. [22]	2021	1	F 57	CAP	BAL	No	Ampi/s, Pip/taz, cefepime	Recovered
Mendez et al. [14]	2021	1	M 48	VAP	BAS	COVID-19	Pip/taz, Meropenem	Recovered
Lim et al. [17]	2023	1	M 23	CAP	BAL	No	Amoxi/cla, clarithro	Recovered
Mo et al. [20]	2026	1	NA	CAP	NA	Diabetes, cirrhosis	NA	NA
Present case	2026	1	M 54	CAP	Sputum	No major comorbidities	Pip/taz, Meropenem	Recovered

CAP: community-acquired pneumonia; HAP: hospital-acquired pneumonia; VAP: ventilator-associated pneumonia; COVID-19: Coronavirus disease; COPD: chronic obstructive pulmonary disease; HIV: Human Immunodeficiency Virus; CKD: chronic kidney disease; CHF: chronic heart failure; NA: not available; mo: months; y: years; M: male; F: female; BAS: bronchial aspirated secretions; Pip/taz: piperacillin/tazobactam; *: not available the number of patients; BAL: bronchoalveolar lavage; Tic/cla: ticarcillin/clavulanate; Amoxi/cla: amoxicillin/clavulanate; RSA: respiratory secretion sample; clarithro: clarithromycin; cotrimox: cotrimoxazole; Ampi/s: ampicillin/sulbactam; Cipro: ciprofloxacin; Levo: levofloxacin; °: for both patients.

Chronic obstructive pulmonary disease (the most common), Human Immunodeficiency Virus infection, chronic kidney disease, heart disease, diabetes, neoplasia. Other patients described in three reports had ventilator-associated pneumonia in the context of a severe COVID-19 disease [12,14,35]. All the patients who died presented hospital-acquired pneumonia and underlying diseases.

When, during the revision process for publication of this paper, the Hafnia strain isolated in our patient was found to be H. paralvei, we made a new search in Pubmed using as keywords simply “Hafnia paralvei”. We obtained 45 papers: the large majority concerned strains isolated from environment, food or animals. Among these studies, only five [36,37,38,39,40] reported human cases (Table 2). None of them described cases of pneumonia. Abbott and coll. [36], the largest case series, reported on microbiologic characteristics of H. paralvei strains isolated from humans, but did not give clinical information about patients.

Table 2. Cases of H. paralvei isolation in humans. 

Reference	Year	N. of Patients	Gender & Age (y)	Infection or Colonization	Specimen	Underlying Diseases	Antibiotic Treatment	Outcome
Abbott, et al. [36]	2011	NA	NA	NA	6 stool, 2 sputum, 2 urine, 1 nasosuction, 1 trachea, 1 wound, 4 unknown	NA	NA	NA
Osuka, et al. [37]	2011	1	M 85	Bacteremia	Blood	CHD, CKD, cholecystitis	Meropenem Ampi/s Amoxi/c	Recovered
Savini, et al. [38]	2013	1	NA	Colonization	Stool	NA	NAP	NAP
Appel, et al. [39]	2023	1	F 59	Colonization	Urine, rectal swab	MS	NAP	NAP
Cho, et al. [40]	2026	1	M 71	Cholangitis	Bile	CholangioK	Colistin, Meropenem	NA
Present case	2026	1	M 54	Pneumonia	Sputum	No major comorbidities	Pip/taz, Meropenem	Recovered

CKD: chronic kidney disease; CHD: chronic heart disease; NA: not available; NAP: not applicable; M: male; F: female; MS: myelodysplastic syndrome; cholangioK: cholangiocarcinoma; Pip/taz: piperacillin/tazobactam; Ampi/s: ampicillin/sulbactam; Amoxi/c: amoxicillin/clavulanate.

Antimicrobial susceptibility profile showed (Table 3) that the isolate was resistant to amoxicillin/clavulanic acid (MIC > 32/2 mg/L), ampicillin (>8 mg/L), piperacillin/tazobactam (>16/4 mg/L), ceftolozane/tazobactam (4/4 mg/L) and colistin (8 mg/L) and remained susceptible to aminoglycosides (gentamicin, amikacin and tobramicin), carbapenems (meropenem and imipenem), fluoroquinolones (levofloxacin and ciprofloxacin), and to new combinations of cephalosporin and carbapenem with beta-lactamase inhibitors (ceftazidime/avibactam and meropenem/vaborbactam).

Table 3. Antimicrobial susceptibility profile of H. paralvei in this case. 

Antibiotic	Sensitivity	MIC (mg/L)
Amoxicillin/clavulanate	R	>32/2
Amikacin	S	≤4
Ampicillin	R	>8
Aztreonam	S	≤1
Cefepime	S	≤1
Ceftazidime	SE	4
Ceftazidime/avibactam	S	≤1/4
Ceftriaxone	S	1
Ciprofloxacin	S	≤0.125
Colistin	R	>4
Ertapenem	S	≤0.25
Gentamicin	S	≤1
Imipenem	S	1
Levofloxacin	S	≤0.25
Meropenem	S	≤0.125
Piperacillin/tazobactam	R	16/4
Tobramycin	S	≤1
Trimethoprim/sulfamethoxazole	S	≤1/19
Ceftolozane/tazobactam	R	4/4
Meropenem/vaborbactam	S	≤2/8

S: sensitive; R: resistant; SE: sensitive increased exposure; MIC: minimum inhibitory concentration.

To determine whether the isolate should be assigned to Hafnia paralvei or Hafnia alvei, in silico analysis of sequences using three independent genome-based methods was performed. Pathogenwatch initially identified the isolate as H. paralvei, with a Mash distance of 0.0114865. This assignment was subsequently confirmed by TYGS, which yielded a dDDH (formula d4) value of 93.9% against the H. paralvei type strain ATCC 29927, whereas the corresponding value obtained against the H. alvei type strain ATCC 13337 was 25.4%. Consistent results were obtained with GTDB-Tk, which assigned the isolate to H. paralvei with an ANI value of 99.07% relative to reference genome GCF_001655005.1, while the ANI value against H. alvei reference genome GCF_034424155.1 was 84.44%. Overall, all three approaches, each relying on a different taxonomic metric (Mash distance, dDDH, and ANI), consistently assigned the isolate to H. paralvei, providing strong evidence that the isolate belongs to this species. Finally, resistance-associated genes, identified using Resfinder, showed that the isolate harbored bla_ACC-1a and bla_mcr-9.1. H. paralvei usually carries a chromosomally encoded, inducible class C β-lactamase ACC-1, which can confer resistance to a broad range of β-lactams [41]. Colistin-resistance of this bacterium has been well described. Hafnia genus (including H. alvei and H. paralvei) are intrinsically resistant to colistin and WGS has occasionally identified plasmid-borne or chromosomal mcr-9 genes [42,43]. The presence of bla_mcr-9, if located on plasmid, could represent a potential reservoir of colistin resistance. Moreover, Turbett and coll. [44] recently underscored the intrinsic resistance to colistin of the genus Hafnia: 117 out of their 119 Hafniaceae isolates resulted colistin-resistant; interestingly, just two isolates from travelers (both H. paralvei) harbored plasmid-borne bla_mcr-9. They report that the identification of colistin-resistance mechanisms was inconclusive due to the limited variability in the phenotypic susceptibility profile of their isolates, which prohibited the identification of variants or genes associated with resistant phenotypes. Another group of Authors described the complete genome sequence of a Hafnia paralvei harboring bla_mcr-9 on a plasmid [45]. Furthermore, plasmid-mediated colistin resistance bla_mcr-9 has been increasingly detected in Enterobacterales [42] and the finding of the bla_mcr-9.1 in our isolate highlights the potential risk of horizontal gene transmission. It is cause for concern because colistin is used as a final line of treatment for life threatening infections caused by multidrug resistant Gram-negative bacteria. Our results underline the importance of relying on molecular or screening tests in combination with MIC-based susceptibility testing and phenotypic tests.

In the ER our patient was initially treated with piperacillin/tazobactam and later with meropenem; no details were provided in the clinical notes for the reasons for this change in therapy, so on admission we prescribed empiric therapy with piperacillin/tazobactam and azithromycin. Due to worsening of clinical conditions, we empirically replaced piperacillin/tazobactam with meropenem. The patient gradually improved and when the antibiogram was available, we decided to continue meropenem. We acknowledge that this decision is probably a limitation: H. alvei harbors AmpC β-lactamases and, in a carbapenem-sparing vision, cefepime could have been chosen. Quite recently (8 August 2026), the updated IDSA 2026 Guidance [46], as new evidence emerged, included H. alvei among the Enterobacterales species at moderate risk for clinically significant inducible ampC and accordingly suggested cefepime for the treatment of infections caused by E. cloacae complex, K. aerogenes, C. freundii, H. alvei. Also, the duration of meropenem therapy (from day +5 to +19) could have been shortened, but the initially unfavorable clinical course induced us to extend effective antibiotic therapy for up to two weeks. The recent American Thoracic Society (ATS) Guideline suggests less than 5 days of antibiotics (minimum 3 days) for adult inpatients with non-severe CAP and 5 or more days in case of severe CAP [47]. Our patient had no ATS criteria for severe CAP.

Several elements support the etiological role of H. paralvei in the pneumonia of our patient. First, the Hafnia strain was the only microorganism isolated. Monomicrobial growth is rare for this organism, occurring in only 25% of isolates in the study with the largest available dataset [1] and is more strongly correlated with actual infection than isolation within a mixed microbial flora [29]. The isolation of a single Enterobacterales species also makes sample contamination less likely: indeed, the diagnostic pathway proposed by the Italian Association of Clinical Microbiologists (AMCLI) limits the identification of Enterobacterales in unprotected respiratory samples (such as induced sputum) to cultures showing no more than two colony types [48].

Second, the bacterial load (10⁷ CFU/mL) exceeds the significance thresholds adopted in Italy. The AMCLI diagnostic pathway indicates that pneumonia-causing pathogens are generally present in respiratory secretions at concentrations of ≥10⁵–10⁶ CFU/mL [48]. An inter-society document, approved by Italian scientific societies specialized in infectious diseases, microbiology, and intensive care, adopts a threshold of 10⁶ CFU/mL for quantitative cultures of potentially contaminated lower respiratory tract samples [49]. The bacterial load of the isolate in our clinical case exceeded these thresholds by one to two orders of magnitude.

Thirdly, despite extensive diagnostic efforts, no alternative cause for the pneumonia was identified: testing for L. pneumophila and S. pneumoniae urinary antigens, multiplex PCR for respiratory pathogens, and blood cultures all yielded negative results. Neither thoracentesis nor bronchoscopy was performed, as the pleural effusion was minimal and a microbiological diagnosis had already been established, with tuberculosis ruled out via negative microscopy and PCR on the same sample.

Finally, the clinical course was consistent with the isolate’s susceptibility profile. The patient experienced clinical deterioration on the fifth day of therapy with piperacillin/tazobactam, an antibiotic to which our isolate showed resistance, though it is generally active against the most common causative agents of CAP, with improvement occurring after switching to meropenem. Following the discontinuation of linezolid on day seven, the pneumonia resolved with meropenem monotherapy alone. A similar course has been described in a previously healthy adult with H. alvei CAP (confirmed via bronchoalveolar lavage): a lack of response to β-lactam/β-lactamase inhibitor combinations, followed by a clinical response to cefepime [22].

In our view, the isolation of a single microorganism—present in high bacterial load and resistant to the ongoing antibiotic regimen—followed by improvement after switching to effective therapy, is consistent with a causative role for that organism in the infection.

The patient had a poor dental condition, as described by dental scan. H. alvei has been associated with periodontal inflammation in several reports [50,51]. It is known that the periodontal biofilm may be a source of dissemination and development of systemic infection, including pneumonia. Even if not demonstrable, in this patient H. paralvei could have reached the lungs after aspiration from the oral cavity.

5. Conclusions

In conclusion, we have described a case of community-acquired pneumonia due to H. paralvei in an immunocompetent man, successfully treated by medical therapy. Limitations in antibiotic choices and duration of treatment have been discussed. Genomic characterization of antibiotic resistance has been studied. Future investigations, including examinations of additional genomic data and functional studies, may contribute to the understanding of the mechanisms of antibiotic resistance in Hafnia spp.