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<strong>Hafnia</strong> <strong>alvei*</strong><br />

Respiratory Tract Isolates in a Community<br />

Hospital Over a Three-Year Period and a Literature<br />

Review<br />

An Klapholz, M.D., F.C.C.P.; Klaus-Dieter Lessnau, M.D.;<br />

Benson Huang, M.D.; Wilfredo Talavera, M.D., F.C.C.P.; and<br />

John F. Boyle, Ph.D.<br />

In a retrospective review, a group of seven patients<br />

were found to have a sputum culture positive for<br />

<strong>Hafnia</strong> alvei. <strong>Hafnia</strong> alvei is a Gram-negative enteric<br />

and oropharyngeal bacillus and usually is<br />

nonpathogenic. All our patients had a chronic underlying<br />

illness and one of the patients was<br />

endotracheally intubated at the time of the isolation<br />

of this organism. Six of seven patients had other<br />

H afnia alvei is a facultative Gram-negative enteric<br />

bacillus belonging to the Enterobacteri-<br />

aceae family. It is rarely considered a pathogenic<br />

organism. Although one of the enteric flora, H alvei<br />

can be a colonizer of the oropharynx and may be a<br />

cause of pneumonia in the community or hospital<br />

setting. It has been reported as a cause of pulmo-<br />

nary infection in the literature in three patients.1’2<br />

We describe a series of patients in whom H alvei<br />

was isolated in respiratory secretions in both the<br />

community and hospital environment and review<br />

the most recent literature on this organism.<br />

MATERIALS AND METHODS<br />

We reviewed the medical records and chest radiographs of<br />

seven patients who were found to have positive cultures of H<br />

alvel in oropharyngeal or bronchial secretions. These patients<br />

had been admitted to a Midtown Manhattan teaching hospital<br />

from January 1989 to January 1992. Identification and sensitivity<br />

testing was performed in our microbiology laboratory. Isolation<br />

of the organism was performed on a trypticase soy agar plate<br />

supplemented with 5 percent CO2 for 18 to 24 h following 24 h<br />

of incubation at 35#{176}C (BBL Microbiology Systems, COC.<br />

Keysville, Md). Isolates were tested on the MicroScan Gram-<br />

negative MIC dry microdilution panel (MicroScan Division,<br />

Baxter Healthcare Corp., West Sacramento, Cal) by using the<br />

Autoscan-4 automated panel reader and computerized data<br />

management system. Sensitivity testing included 33 commonly<br />

used antibiotics. A computer-assisted review of the literature<br />

was done by Medline and additional databases.<br />

RESULTS<br />

Seven patients were identified as having sputum<br />

*From the Division of Pulmonary/Critical Care Medicine (Drs.<br />

Klapholz, Lessnau, Huang, and Talavera), and the Department<br />

of Clinical Microbiology (Dr. Boyle), Cabrini Medical Center,<br />

New York; and New York Medical College (Drs. Klapholz and<br />

Talavera), New York.<br />

Manuscript received April 23, 1993; revision accepted July 20.<br />

Reprint requests: Dr. Klapholz, Cabrini Medical Center, 227<br />

East 19th Street, New York 10003<br />

organisms isolated along with H alvei, and only one<br />

patient had a pure growth of H alvei confirmed by<br />

a culture obtained from a bronchoscopic protected<br />

brush specimen. All isolates displayed resistance to<br />

conventional antibiotics including cephalosporins<br />

and penicillins. Although rare, H alvei may be a<br />

potential pathogen in a patient with a chronic<br />

underlying illness. (Chest 1994: 105 ;1098-1100)<br />

cultures positive for H alvei as shown in Table 1.<br />

There were 5 men and 2 women with a mean age<br />

of 60 years. All the isolates were in patients with<br />

a chronic underlying illness. Isolates from patients 1<br />

to 4 were obtained within 48 h of admission and<br />

therefore presumed to be community-acquired iso-<br />

lates. The remaining patients were presumed to<br />

have nosocomial colonization. In six patients, H<br />

alvei was isolated with other pathogens, and there-<br />

fore none of the pulmonary findings could be defi-<br />

nitely attributed to H alvei alone. Clinical presenta-<br />

tion and chest x-ray film findings on admission were<br />

not helpful because of concomitant infectious and<br />

noninfectious processes. For patient 7, fiberoptic<br />

bronchoscopy was performed with a protected sheath<br />

brush which on culture revealed pure colonies of H<br />

alvei and confirmed the sputum culture of H alvei as<br />

1098 <strong>Hafnia</strong> atval in a Community Hospital (Klapholz eta!)<br />

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well.<br />

Antibiotic sensitivities are summarized in Table 2.<br />

Five isolates were resistant to ampicillin. Five of<br />

seven isolates were resistant to a first-generation<br />

cephalosporin, and four of seven isolates were resis-<br />

tant to a second-generation cephalosporin. Two of<br />

seven isolates were resistant to a semisynthetic<br />

penicillin. All isolates were sensitive to the<br />

aminoglycosides, imipenem-cilastin, and the<br />

quinolones.<br />

DISCUSSION<br />

In the past, <strong>Hafnia</strong> was considered a member of<br />

the genus Enterobacter and was called Enterobacter<br />

hafnia or “paracolon” bacterium.3 With DNA and<br />

biochemical studies, it has been defined as a sepa-<br />

rate genus of the Kiebsiella family composed of<br />

bacteria motile at 25#{176} to 36#{176}Cand immotile at higher<br />

temperatures. <strong>Hafnia</strong> alvei is a small, plump bacillus


Age, yr/Ethnic Admitting Signs,<br />

Patient Group, Sex* History Symptoms, and Hospital Course Sputum Chest X-ray Film<br />

1 40/H/F Steroid-dependent<br />

Table 1-Patients With <strong>Hafnia</strong> alvei in Respiratory Secretions<br />

asthma, diabetes<br />

mellitus, intravenous<br />

drug use<br />

2 83/W/M Myelodysplastic<br />

syndrome, hyper-<br />

tension<br />

3 60/H/M Adenocarcinoma of<br />

the lung; left-sided<br />

hydropneumothorax,<br />

recent chemo-<br />

therapy<br />

4 76/W/M COPD, arterioscle-<br />

rotic heart disease,<br />

atrial fibrillation,<br />

Iupus anticoagulant<br />

5 63/W/M Chronic renal failure,<br />

idiopathic<br />

thrombocytopenic<br />

purpura<br />

6 36/W/M Human immunodefi-<br />

ciency virus positive<br />

for 1 year<br />

7 68/H/F COPD, congestive<br />

*W=white; H=Hispanic.<br />

heart failure,<br />

chronic renal<br />

failure,<br />

hypothyroidism<br />

Increasing dyspnea, expiratory<br />

wheezing; treated initially with<br />

steroids and bronchodilators<br />

Hoarseness, fever, chills, leukocytosis;<br />

laryngoscopy revealed mild glottic<br />

edema responding to cefuroxime<br />

within 3 d; steroids never adminis-<br />

tered<br />

Hemoptysis; fiberoptic bronchoscopy<br />

revealed tumor with left lower lung<br />

occlusion; remained afebrile, no<br />

antibiotics given<br />

Cough, dyspnea, minor hemoptysis;<br />

cytologic studies revealed small cell<br />

carcinoma; postobstructive<br />

pneumonia improved symptomati-<br />

cally<br />

Cardiac arrest followed by hemicolec-<br />

tomy because of colonic infarction<br />

and perforated cecum; expired with<br />

overwhelming pneumonia<br />

Productive cough, fever, pleuritic<br />

chest pain, normal leukocyte count;<br />

treated with sulfamethoxazole/<br />

trimethoprim for 14 d; discharged<br />

afebrile<br />

with a slight bipolar appearance on Gram staining.4<br />

Rectal bleeding and urinary tract<br />

infection; cardiopulmonary<br />

It is catalase- and lysine decarboxylase-positive and<br />

it does not hydrolyze arginine, thus differing from E<br />

cloacae.5<br />

<strong>Hafnia</strong> alvei has been associated with a wide array<br />

of clinical infections. It has been reported as a cause<br />

of meningitis,6 diarrhea,”7 necrotizing enterocolitis,8<br />

pneumonia 1,2 urinary tract infection , endophthal-<br />

mitis,9 and soft tissue infection.’0 In addition, Dibb”<br />

reported that H alvei was the only Gram-negative<br />

rod isolated from the outer ear canal in healthy<br />

Norwegian individuals.<br />

Washington et al’ reported the isolation of H alvei<br />

from the respiratory tract in 5 patients from a total<br />

of 760 isolates of Enterobacter over a 3-year period.<br />

Three of the patients were described as having<br />

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arrest, intubation; extubation,<br />

but general condition worsened;<br />

with aztreonam on clearing<br />

radiographic infiltrates; expired<br />

#1 H alvel, Streptococ-<br />

cus pneumonia<br />

Staphylococcus aureus<br />

in blood and throat<br />

culture; 1) S aureus,<br />

Mycobacterlum<br />

gordonae, Klebsiella<br />

pneumonia, H alvel<br />

1) H alvel,<br />

Ac! netoba cter<br />

hemolyticus<br />

1) Citrobacter freundil;<br />

5) Serratia<br />

rnarcescens, M<br />

gordonae; 6) H abet,<br />

Escherichia cob!; 7)<br />

Pseudom.onas<br />

aeruginosa, S<br />

Marcescens<br />

(Bronchoalveolar<br />

lavage); 14) H alvel<br />

3) S aureus, P<br />

aeruglnosa; 14) H<br />

alvei<br />

1) A hemolyticus,<br />

Pneumocystis carinti,<br />

Asperigillus species; 2)<br />

H alvel<br />

7) H alvel; had<br />

fiberoptic<br />

bronchoscopy with<br />

protected sheath<br />

specimen brush; pure<br />

colonies of H abvei<br />

No infiltrate<br />

Minimal fibrotic<br />

changes<br />

Left lower lung<br />

infiltrate<br />

Left lower lung<br />

infiltrate<br />

Bilateral<br />

infiltrates<br />

Bilateral<br />

infiltrates,<br />

large left<br />

upper lobe<br />

bulla<br />

Cardiomegaly,<br />

left lower lung<br />

infiltrate<br />

chronic respiratory disease. Four of these isolates<br />

were from sputum samples and one was from the<br />

trachea, and all were nosocomially acquired. Three<br />

isolates were considered commensals. Two isolates<br />

(one from sputum and one tracheal isolate) were the<br />

predominant organisms in two patients with fatal<br />

bronchopneumonia, one of which also was isolated<br />

from the lung postmortem. In addition, it was<br />

shown to be an uncommon colonizer, isolated in 19<br />

of 760 isolates of Enterobacter found in stool, urine,<br />

the pharynx, oral ulcers, and wounds. As in our<br />

series, H alvei was isolated in mixed cultures and<br />

was a coisolate in 15 of those 19 isolates.<br />

In addition, Frick et a12 reported a case of H alvei<br />

pneumonia diagnosed by pure culture from a<br />

bronchoscopic specimen in a patient receiving me-<br />

CHEST/105/4/APRIL,1994 1099


Table 2-Antibiotic Sensitivities of <strong>Hafnia</strong> alvei Isolates<br />

Patient Resistance to Cephalosporine Additional Resistance Sensitivity<br />

1 None None All others, including ampicillin<br />

2 Cephalothin, cefuroxime (medium-sensitive) Ampicillin, piperacillin All others<br />

3 Cefazolin, cefuroxime, ceftazidime Ampicillin, piperacillin Ceftriaxone, aminoglycosides. cefotetan,<br />

4 Cefazolin, cefuroxime, cefotetan Aztreonam Ampicillin, piperacillin, ciprofioxacin,<br />

5 Cefazolin, cephalothin Ampicillin All others<br />

1100 <strong>Hafnia</strong> atvei in a Community Hospital (K!aplsolz eta!)<br />

aztreonam<br />

aminoglycosides<br />

6 Cephalothin, cefuroxime, ceftriaxone, Ampicillin Cefotetan, all others including<br />

ceftazidime trimethoprim/sulfamethoxazole<br />

7 None Ampicillin Aztreonam, all others<br />

chanical ventilation for 12 days. Although it is<br />

unclear from this report whether the specimen was<br />

obtained via a protected brush or bronchoalveolar<br />

lavage, the pure growth of H alvei strongly suggests<br />

that this was the offending pathogen.<br />

In our case series, H alvel was isolated from<br />

sputum at the time of admission in four of the seven<br />

cases (cases 1 to 3 and 6), suggesting that it is a<br />

community colonizer. In all of those patients, it was<br />

a coisolate with other organisms, and a clinical<br />

response was obtained without specific treatment<br />

for H alvei. Laboratory contamination was not sus-<br />

pected because there was no clustering of these<br />

isolates from a particular ward or over a specific<br />

period of time. In addition, three of the four com-<br />

munity isolates were in patients with underlying<br />

pulmonary disease. Whether this predisposed those<br />

patients to colonization as in the study of Washing-<br />

ton et a18 is not known. Of the nosocomial isolates,<br />

only patient 7 had a nosocomially acquired pneumo-<br />

nia in which H alvei was the offending pathogen.<br />

Although colony counts were not performed on the<br />

sterile brush specimen, subsequent clinical and<br />

radiographic improvement with an appropriate anti-<br />

biotic strongly implied H abel as the offending<br />

pathogen. Patient 4 had a nosocomially acquired<br />

isolate without evidence of disease. In patient 6, H<br />

alvel could have been a pathogen, but further<br />

diagnostic studies were not done.<br />

There was a pattern observed regarding the sen-<br />

sitivity of these isolates, with the majority of them<br />

resistant to ampicillin and some first- and second-<br />

generation cephalosporins (Table 2). This pattern of<br />

resistance is consistent with other case reports<br />

reviewed in the literature.”2’8”2 Six of seven patients<br />

had underlying chronic disease.<br />

Although in the majority of our cases, there was<br />

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no clinical importance in isolating H alvei other<br />

than colonization, it may occasionally be the primary<br />

cause of pneumonia. In the era of rapidly<br />

evolving resistant organisms, immunosuppression<br />

and prolonged ventilator management, one must be<br />

wary of the emergence of H abel as a possible<br />

pulmonary pathogen.<br />

REFERENCES<br />

1 Washington JA, Birk RJ, Ritts RE. Bacteriologic and<br />

epidemiologic characteristics of Enterobacter hafnla and<br />

Enterobacter liquefaciens. J Infect Dis 1971; 124:379-86<br />

2 Frick T, Kunz M, Vogt M, Turina M. Typical nosocomial<br />

infection with an unusual cause: Hafnla alvel-report of 2<br />

cases and literature review. Schweiz Rund Med Praxis 1990;<br />

79:1092-94<br />

3 Fields BN, Uwayda MM, Kunz U, Swartz MN. The so-called<br />

“paracolon” bacteria. Am J Med 1967; 42:89-106<br />

4 Englund GW. Persistent septicemia due to <strong>Hafnia</strong> alvei. Am<br />

J Clin Pathol 1969; 51:717-19<br />

5 Eisenstein BI. Enterobacteriaceae. In: Mandell CL, Douglas<br />

RG, Bennet JE, eds. Principles and practice of infectious<br />

disease. 3rd ed. New York: Churchill Livingston, 1990; 1668<br />

6 Mojtabaee A, Siadati A. Enterohacter hafnla meningitis. J<br />

Pediatr 1978; 93:1062-63<br />

7 Albert MJ, Khorshed A, Moyenul I, Montanaro J, Rahman<br />

H, Haider K, at al. Hafnla alvel, a probable cause of<br />

diarrhea in humans. Infect Immunol 1991; 59:1507-12<br />

8 Ginsberg HG, Goldsmith JP. <strong>Hafnia</strong> alvei septicemia in an<br />

infant with necrotizing enterocohtis. J Perinatol 1988; 3:122-<br />

23<br />

9 Caravalho J Jr. McMillan VM, Ellis RB, Betancourt A.<br />

Endogenous ophthalznitis due to Salmonella arlzonae and<br />

Hafnla alvel. South Med J 1990; 83:325-27<br />

10 Berger S. Edberg SC, Klein RS. Enterobacter hafnla infection:<br />

report of 2 cases and review of the literature. Am J Med<br />

Sci 1977; 273:101-04<br />

11 Dibb WL. The normal microbial flora of the outer ear canal<br />

in healthy Norwegian individuals. Niph Ann 1990; 13:11-16<br />

12 Qadi HSM, Belobraydic KA. In vitro activity of aztreonam<br />

against Gram-negative bacteria from clinical specimens and<br />

its comparison with other commonly used antibiotics. Meth<br />

Find Exp Clin Pharmacol 1986; 8:223-26

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